Impact of Alirocumab on Neoatherosclerosis Formation and Vessel Healing after Drug-eluting Stent Implantation in Patients with Acute Myocardial Infarction: a Substudy of the PACMAN-AMI Trial

Impact of Alirocumab on Neoatherosclerosis Formation and Vessel Healing after Drug-eluting Stent Implantation in Patients with Acute Myocardial Infarction: a Substudy of the PACMAN-AMI Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Alirocumab on Neoatherosclerosis Formation and Vessel Healing after Drug-eluting Stent Implantation in Patients with Acute Myocardial Infarction: a Substudy of the PACMAN-AMI Trial Ryota Kakizaki, Yasushi Ueki, Konstantinos C Koskinas, Hiroki Shibutani, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6592491/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Aug, 2025 Read the published version in The International Journal of Cardiovascular Imaging → Version 1 posted 11 You are reading this latest preprint version Abstract Purpose: Higher on-treatment levels of low-density lipoprotein cholesterol in statin-treated patients were reportedly associated with the occurrence of neoatherosclerosis after drug-eluting stent (DES) implantation. We aimed to investigate the impact ofalirocumab added to high-intensity statin therapy on neoatherosclerosis formation among patients with acute myocardial infarction (AMI) treated with DES. Methods: This was a pre-specified substudy of the PACMAN-AMI trial, a randomized, double-blind trial comparing alirocumab versus placebo added to high-intensity statin therapyin AMI patients. The present study included patients undergoing optical coherence tomography assessment of DES in the culprit lesion at one year. The frequency of neoatherosclerosis, neointimal thickness, and strut malapposition were compared between treatment groups. Results: Among 191 patients (95 with alirocumab and 96 with placebo), neoatherosclerosis was observed in 13 patients (6.8%) at one year. There was no significant difference in the frequency of neoatherosclerosisbetween treatment groups (alirocumab 4.2% vs. placebo 9.4%, P=0.25). Among 11 patients with lipid-laden neointima, minimal fibrous cap thickness was greater in the alirocumab group than in the placebo group (217.5±122.5 vs. 87.8±49.1 μm, P=0.02). Neointimal thickness (136.2±71.1 vs. 151.4±101.4 μm, P=0.45) and the frequency of malapposed struts (0.94 vs. 0.53%, P=0.27) were comparable between treatment groups. Conclusions: Among AMI patients treated with DES, there was no significant impact of alirocumab on the frequency of neoatherosclerosis and vessel healing at one year. The observed numerical difference and the finding of more stable neoatheroma in the alirocumab group need further investigation in larger studies with extended follow-up. proprotein convertase subtilisin/kexin type 9 inhibitor low-density lipoprotein cholesterol neoatherosclerosis neointimal hyperplasia Figures Figure 1 Introduction Drug-eluting stents (DES) have improved the overall safety and efficacy of percutaneous coronary intervention (PCI) [ 1 ]. However, late stent failures including in-stent restenosis and stent thrombosis continue to occur at relatively low, but constant rates [ 2 – 4 ]. Neoatherosclerosis, histologically characterized by the accumulation of lipid-laden macrophage foam cells, necrotic core, and calcification in the neointimal tissue of the stented segment [ 5 ], is increasingly recognized as a major pathophysiological mechanism underlying late stent failures [ 6 – 8 ]. In culprit lesions of acute myocardial infarction (AMI), delayed vessel healing, characterized by less neointimal thickness, higher prevalence of uncovered struts, and greater inflammation, leads to more severe endothelial dysfunction and impaired endothelial barrier, potentially resulting in an accelerated formation of neoatherosclerosis [ 9 ]. Although procedure-related factors including stent type (i.e. strut thickness, polymer type), strut apposition, and underlying plaque type are important substrates for neoatherosclerosis formation and vessel healing following DES implantation, previous studies have consistently demonstrated a significant positive association between serum low-density lipoprotein cholesterol (LDL-C) levels and the occurrence of neoatherosclerosis [ 10 – 12 ]. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) added to statins potently reduce LDL-C and thereby result in significant plaque regression and cardiovascular benefits compared with statin therapy alone [ 13 , 14 ]. To date, the effect of intensive lipid-lowering therapy with PCSK9i on top of high-intensity statin on neoatherosclerosis formation and late stent healing remains to be elucidated. Therefore, we have performed a predefined substudy of the randomized, double-blind PACMAN-AMI (effects of the PSCK9 antibody AliroCuMab on coronary Atherosclerosis in patieNtswith Acute Myocardial Infarction) trial to assess whether intensive lipid-lowering therapy with alirocumab impacts on the frequency of neoatherosclerosis and vessel healing. Methods Study population The PACMAN-AMI trial (NCT03067844) was an investigator-initiated, multicenter, randomized, double-blind clinical trial conducted at 9 centers in 4 European countries (Switzerland, Austria, Denmark, and the Netherlands). The study design and main results of the PACMAN-AMI trial has been reported previously [ 14 , 15 ]. In brief, the PACMAN-AMI trial included 300 patients with 18 years or older who underwent PCI of the culprit lesion for treatment of ST-elevation or non-ST-elevation myocardial infarction. Patients were randomized to receive biweekly alirocumab or placebo for 52 weeks in addition to high-intensity statin therapy (rosuvastatin 20 mg). The present pre-specified substudy included patients who underwent optical coherence tomography (OCT) imaging for the culprit lesion of AMI at 52 weeks following primary PCI. OCT recording was performed if the operator deemed it feasible for the culprit lesion at one year follow-up. PCI was performed in accordance with the European Society of Cardiology Guidelines [ 16 ] and DES selection was at the discretion of the operator. All patients provided written informed consent, and the study was approved by the ethical committee at each site. Acquisition and Analysis of Intracoronary Imaging The OCT imaging was performed using a frequency-domain OCT system (Dragon Fly, LightLab, St. Jude Medical, St. Paul, MN, USA). OCT images were analyzed at independent core laboratory (Bern University Hospital, Bern, Switzerland) by experienced analysts. Cross-sectional OCT images were evaluated quantitatively and qualitatively with an interval of 0.4 mm within the stented segments using proprietary software (QCU-CMS version 4.69 software, LKEB, Leiden, The Netherlands). Neointima was defined as the tissue between the luminal border and the endoluminal border of the struts. Neoatherosclerosis was defined as either the presence of lipid-laden neointima or calcification with a longitudinal extension of ≥ 1.2 mm, the presence of macrophage, or the presence of cholesterol crystals [ 17 ]. Fibroatheroma were characterized as a signal-poor region displaying high attenuation (to differentiate from layered neointima) with diffuse borders and a lateral extension of at least one quadrant [ 18 ]. Calcification were defined as signal-poor regions with low attenuation and clear borderlines. Macrophage was defined as lines or dots with strong signal attenuation producing a shadow with a sharply delineated lateral border. In-stent cholesterol crystal was defined as thin and linear structures with high backscattering without attenuation within the neointima. Stent strut coverage and malapposition were defined and measured as described previously [ 18 ]. Study endpoints Primary endpoint was the frequency of neoatherosclerosis at 1 year, and key secondary endpoints were neointimal area, neointimal thickness, and percentage of uncovered and malapposed struts at 1 year. Statistical analysis Continuous variables were summarized as mean (standard deviation) or median [interquartile range]. Between-group comparisons were conducted using Student t-tests or Wilcoxon-Mann-Whitney tests, as appropriate. Categorical variables were summarized as counts (percentage) and compared between groups using Fisher’s exact tests. Statistical significance was set to 0.05. All statistical analyses were performed using Stata 17 (StataCorp LLC, College Station, TX) and R 4.4.1 (R Core Team). Results Baseline and procedural characteristics A total of 191 patients (95 in the alirocumab group and 96 in the placebo group) undergoing OCT imaging for the culprit stents at 1 year were analyzed for the current sub-study ( Supplementary Fig. 1 ). Baseline clinical and procedural characteristics were well-balanced between treatment groups (Tables 1 and 2 ). There were no significant differences in baseline characteristics between patients with and without OCT for the culprit lesion at 1 year follow-up, except for the frequency of dyslipidemia and P2Y12 inhibitor at baseline ( Supplementary Table 1 ). LDL-C level at follow-up was 23.2 ± 23.2 mg/dL in the alirocumab group and 73.5 ± 30.9 mg/dL in the placebo group. Table 1 Patient characteristics and medication Overall n = 191 Alirocumab n = 95 Placebo n = 96 P value Age, years 58.1 (9.5) 57.9 (10.1) 58.4 (8.9) 0.69 Men, n (%) 160 (83.8) 83 (87.4) 77 (80.2) 0.24 BMI, kg/m2 27.9 (4.3) 27.3 (3.9) 28.4 ( 4.6 0.06 Medical history, n (%) Arterial hypertension 81 (42.4) 34 (35.8) 47 (49.0) 0.08 Dyslipidemia 162 (84.8) 79 (83.2) 83 (86.5) 0.55 Diabetes 16 (8.4) 5 (5.3) 11 (11.5) 0.19 Current smoking 87 (45.5) 49 (51.6) 38 (39.6) 0.11 Previous myocardial infarction 2 (1.0) 1 (1.1) 1 (1.0) 1.00 Previous PCI 3 (1.6) 1 (1.1) 2 (2.1) 1.00 Peripheral arterial disease 3 (1.6) 1 (1.1) 2 (2.1) 1.00 Family history of CAD 59 (30.9) 28 (29.5) 31 (32.3) 0.75 Type of acute myocardial infarction, n (%) 0.47 NSTEMI 85 (44.5) 45 (47.4) 40 (41.7) STEMI 106 (55.5) 50 (52.6) 56 (58.3) Peak CK, IU/L 687 (1061) 770 (1191) 605 (915) 0.29 Peak hs-cTnT, ng/mL 1189 (2734) 1417 (3311) 961 (1991) 0.25 LVEF, % 53 (11) 53 (11) 53 (11) 0.92 Medication, n (%) Statin 26 (13.6) 11 (11.6) 15 (15.6) 0.53 High-intensity statin therapy 13 (6.8) 6 (6.3) 7 (7.3) 1.00 Ezetimibe 0 (0.0) 0 (0.0) 0 (0.0) Antiplatelet therapy Aspirin 13 (6.8) 7 (7.4) 6 (6.2) 0.78 P2Y12 inhibitor 3 (1.6) 0 (0.0) 3 (3.1) 0.25 Anti-coagulant 2 (1.0) 1 (1.1) 1 (1.0) 1.00 β-Blocker 15 (7.9) 5 (5.3) 10 (10.4) 0.28 ACEI 13 (6.8) 5 (5.3) 8 (8.3) 0.57 ARB 20 (10.5) 7 (7.4) 13 (13.5) 0.24 Values are count (percentage) or mean (SD). Abbreviations: ACEI: angiotensin converting enzyme inhibitor, ARB: angiotensin receptor blocker, BMI: body mass index, CAD: coronary artery disease, CK: creatinine kinase, cTnT: cardiac troponin T, LVEF: left ventricular ejection fraction, NSTEMI: non-ST-segment elevation myocardial infarction, PCI: percutaneous coronary intervention, STEMI: ST-segment elevation myocardial infarction Table 2 Lesion and procedure characteristics Overall n = 191 Alirocumab n = 95 Placebo n = 96 P value Target vessel location, n (%) 0.20 Left anterior descending 93 (48.7) 47 (49.5) 46 (47.9) Left circumflex 42 (22.0) 25 (26.3) 17 (17.7) Right coronary artery 56 (29.3) 23 (24.2) 33 (34.4) Final TIMI flow, n (%) 0.50 0 0 (0.0) 0 (0.0) 0 (0.0) 1 0 (0.0) 0 (0.0) 0 (0.0) 2 1 (0.5) 1 (1.1) 0 (0.0) 3 190 (99.5) 94 (98.9) 96 (100.0) Number of stents, n (%) 1.0 [0.0] 1.0 [0.0] 1.0 [0.0] 0.72 Total stent length, mm 28.0 [20.0] 26.0 [20.0] 28.0 [17.0] 0.36 Stent diameter, mm 3.5 [1.0] 3.5 [1.0] 3.5 [1.0] 0.60 Polymer type, n (%) 0.88 Biodegradable polymer 98 (51.3) 49 (51.6) 49 (51.0) Durable polymer 89 (46.6) 43 (45.3) 46 (47.9) Post-dilatation, n (%) 160 (83.8%) 78 (82.1%) 82 (85.4%) 0.56 Bifurcation lesion, n (%) 30 (15.7) 12 (12.6) 18 (18.8) 0.32 Multivessel PCI, n (%) 19 (9.9) 13 (13.7) 6 (6.2) 0.10 GP IIb/IIIa inhibitors, n (%) 33 (17.3) 16 (16.8) 17 (17.7) 1.00 Values are count (percentage), mean (SD), or median [interquartile range]. Multivessel treatment and GP IIb/IIIa are at patient level. All other variables refer to the culprit lesion. Abbreviations: GP: glycoprotein, PCI: percutaneous coronary intervention, TIMI: thrombolysis in myocardial infarction OCT findings OCT findings are shown in Table 3 . Neoatherosclerosis was observed in 13 (6.8%) patients, 4 (4.2%) in the alirocumab group and 9 (9.4%) in the placebo group ( p = 0.25). The frequency of fibroatheroma, fibrocalcific plaque, macrophage, and cholesterol crystal was 5.8%, 1.0%, 1.0%, and 2.1%, respectively, without statistical differences between treatment groups. Among 11 patients with lipid-laden neointima, fibrous cap thickness was significantly greater in the alirocumab group than in the placebo group (217 ± 123 µm vs. 88 ± 49 µm, p = 0.02). The characteristics of patients with neoatherosclerosis were summarized in Supplementary Table 2 . Biochemical measures and intracoronary imaging findings in patients with and without neoatherosclerosis were shown in Supplementary Table 3 . Absolute change in serum LDL-C level was − 106.5 (-135.4 to -77.5) vs. -104.3 (-111.0 to -97.6) mg/dL in patients with vs. without neoatherosclerosis. Figure 1 shows the correlation between frequency of neoatherosclerosis and LDL-C level in prospective studies. Table 3 OCT analysis at 1 year Overall n = 191 Alirocumab n = 95 Placebo n = 96 P value Duration from implantation, day 376 (15) 377 (14) 374 (16) 0.16 Neoatherosclerosis, n (%) 13 (6.8) 4 (4.2) 9 (9.4) 0.25 Fibroatheroma, n (%) 11 (5.8) 4 (4.2) 7 (7.3) 0.54 *Total length of fibroatheroma, mm 5.78 (4.91) 4.00 (3.35) 6.80 (5.59) 0.32 *Maximum lipid arc, degree 173 (73) 155 (38) 184 (89) 0.79 *Minimum cap thickness, µm 135 (101) 217 (123) 88 (49) 0.02 Fibrocalcified, n (%) 2 (1.0) 0 (0.0) 2 (2.1) 0.50 Macrophage accumulations, n (%) 2 (1.0) 1 (1.1) 1 (1.0) 1.00 In-stent cholesterol crystal, n (%) 4 (2.1) 1 (1.1) 3 (3.1) 0.62 Other findings, n (%) Thrombus 2 (1.0) 2 (2.1) 0 (0.0) 0.50 Microvessel 76 (39.8) 39 (41.1) 37 (38.5) 0.88 Lesion level analysis Analyzed stent length, mm 31.1 (14.1) 30.1 (13.6) 32.0 (14.6) 0.45 Minimal lumen area, mm 2 4.82 (2.21) 5.09 (2.32) 4.55 (2.07) 0.09 Minimal stent area, mm 2 6.05 (2.45) 6.21 (2.39) 5.90 (2.51) 0.37 Cross section level analysis Analyzed cross section per lesion, n (%) 78 (35) 77 (35) 80 (36) 0.53 Mean lumen area, mm 2 6.98 (2.82) 7.13 (2.71) 6.83 (2.93) 0.28 Mean stent area, mm 2 8.06 (2.97) 8.12 (2.69) 8.00 (3.23) 0.57 Neointimal area, mm 2 1.14 (0.85) 1.07 (0.73) 1.20 (0.96) 0.60 Malapposed area, mm 2 0.05 (0.20) 0.07 (0.25) 0.03 (0.12) 0.40 Strut level analysis Analyzed struts per lesion, n (%) 762 (364) 744 (353) 781 (375) 0.48 Mean neointimal thickness, µm 145 (88) 136 (71) 151 (101) 0.45 Rate of uncovered struts, % 2.7 (3.9) 3.1 (4.5) 2.3 (3.3) 0.45 Rate of malapposed struts, % 0.7 (2.4) 0.9 (2.8) 0.5 (2.1) 0.27 Incomplete apposition distance, µm 3.66 (12.04) 4.73 (13.93) 2.61 (9.77) 0.49 Values are count (percentage) or mean (SD). Abbreviations: OCT: optical coherence tomography. *calculated across 11 patients. At a cross sectional level, there were no differences in the frequency of cross sections with uncovered struts (15.0 vs. 12.13%, p = 0.57) and malapposed struts (4.0 vs. 1.7%, p = 0.24), and neointimal area (1.07 ± 0.73 vs. 1.20 ± 0.96 mm 2 , p = 0.60) between the two groups (Table 3 ). Supplementary Fig. 2 shows the correlation between neointimal area and absolute change in LDL-C, and Supplementary Fig. 3 shows the correlation between percentage of uncovered struts and absolute change in LDL-C. At a strut level, the percentage of uncovered struts (3.1 vs. 2.3%, p = 0.45), the percentage of malapposed struts (0.9 vs. 0.5%, p = 0.27) and neointimal thickness (136 vs. 151 µm, p = 0.45) were comparable between two groups (Table 3 ). Patients with neoatherosclerosis had greater neointimal area (2.11 ± 1.08 vs. 1.06 ± 0.79 mm 2 ) and greater neointimal thickness (241 ± 97 vs. 137 ± 83 µm) compared with those without ( Supplementary Table 4 ). Clinical outcomes Supplementary Table 5 shows the incidence of the revascularization at 1 year. Revascularization was performed in 35 patients (18.3%). Among them, 11 patients (5.8%) underwent ischemia-driven target lesion revascularization, 2 (15.4%) with neoatherosclerosis and 9 (5.1%) without neoatherosclerosis. Ischemia-driven non-target lesion revascularization was performed in 19 patients (9.9%), 1 (7.7%) in patients with neoatherosclerosis and 18 (10.1%) in patients without neoatherosclerosis. Discussion This is the first study to investigate the effect of very low LDL-C level achieved by alirocumab on neoatherosclerosis formation and vessel healing among AMI patients undergoing PCI with current generation DES. The main findings of the present study, based on OCT performed in the stented culprit lesion 1 year after primary PCI, are: (1) there were no significant differences in the frequency of neoatherosclerosis between the alirocumab and placebo groups in the context of a background high-intensity statin treatment in both treatment arms (rosuvastatin 20 mg). However, neoatheroma in the alirocumab group was more stable as suggested by a significantly greater minimal fibrous cap thickness, (2) the degree of vessel healing represented by neointimal growth, strut coverage, and strut apposition did not significantly differ between the treatment groups at 1 year following primary PCI. Frequency of neoatherosclerosis Although there are several relevant differences in pathogenic mechanisms between in-stent neoatherosclerosis and native atherosclerosis, lipid diffusion and inflammatory cell migration through the endothelium are considered common pathways of atherosclerosis formation for both disease entities. Previous retrospective observational studies have demonstrated a significant correlation between the serum LDL-C level and the frequency of neoatherosclerosis [ 10 – 12 , 19 , 20 ]. In the current study, the frequency of neoatherosclerosis was numerically lower in the alirocumab group (4.2% vs. 9.4%), but there was no significant difference between groups despite very low LDL-C levels achieved in the alirocumab group (mean 23.2 mg/dL vs. 73.5 mg/dL). A potential explanation may be the lack of power (i.e. type II error) in view of only 13 patients with neoatherosclerosis at 1 year. The relatively short follow-up period of 1 year in our pre-specified sub-study may at least partly contribute to small number of neoatherosclerosis formation. Another explanation may be the initiation of high-intensity statin therapy (rosuvastatin 20 mg) in both groups from the first day after primary PCI, which was not the case in previous studies. Statins not only decrease LDL-C level but also reduce inflammation, which can lead to endothelial cell activation and dysfunction [ 21 ] and thus result in neoatherosclerosis formation. The level of high sensitive C-reactive protein (hsCRP) was reportedly associated with the accumulation of lipids within the neointima [ 10 ]. Unlike statins, PSCK9i have little no effect on inflammation [ 22 ] and accordingly, the on-treatment hsCRP level was similar in both treatment groups in our study (2.0 vs. 2.5 mg/L, p = 0.71). Interestingly, neoatheroma in the alirocumab group had a significantly greater minimal fibrous cap thickness. This finding may suggest that intensive lipid-lowering afforded by alirocumab resulted in more stable neoatheroma, along the lines of the effects of alirocumab observed in the main study investigating native atherosclerosis [ 23 ]. The frequency of neoatherosclerosis in the alirocumab group in the current study (4.2%) appeared to be among the lowest ever reported compared with previous prospective observational studies that typically found neoatherosclerosis in 11.4–15.9% between 1–3 years with on-treatment LDL-C levels between 63–80 mg/dL [ 17 , 24 , 25 ] (Fig. 1 ). Moreover, the frequency of neoatherosclerosis in the placebo group of the present study (9.4%) was also numerically lower compared to that reported in previous studies despite a similar on-treatment LDL-C level. The lower frequency in the current study may be explained by the routine use of high-intensity statin therapy, stent types, and clinical presentation. In particular, a previous pathological study reported that neointimal thickness in culprit site of AMI was significantly smaller than in coronary lesions in stable patients [ 9 ]. Given the pathological role of in-stent neointima as a basis for neoatherosclerosis formation, the lower frequency of neoatherosclerosis might be attributed to smaller neointimal tissue in the AMI culprit lesions in the current study. Interestingly, we noted some patients with neoatherosclerosis formation within 12 months with very low on treatment LDL-C values (Table 4 ), i.e. 3 patients with < 20mg/dL. This underlines that on-treatment LDL-C should not be considered as an isolated driver of neoatherosclerosis. In these patients, hsCRP levels at follow-up were 0, 0, and 0.8 mg/L, respectively. These three patients suggest that other, incompletely understood mechanisms unrelated to LDL-C and inflammation may come into play. Table 4 Clinical outcomes Overall n = 191 Neoatherosclerosis (+) N = 13 Neoatherosclerosis (-) N = 178 Any revascularization n (%) 35 (18.3) 3 (23.1) 32 (18.0) Ischemia driven revascularization n (%) 30 (15.7) 3 (23.1) 27 (15.2) Ischemia driven target lesion revascularization n (%) 11 (5.8) 2 (15.4) 9 (5.1) Ischemia driven non-target lesion revascularization n (%) 19 (9.9) 1 (7.7) 18 (10.1) Values are count (percentage). Neointimal growth and strut malapposition In the current study, there was no significant difference in the degree of neointimal hyperplasia, strut coverage, and strut apposition. Although there have been potential concerns of late-acquired malapposition due to pronounced plaque regression induced by intensive LDL-C lowering with alirocumab, reassuringly, we did not observe such a phenomenon in the current analysis showing a low and similar frequency of malapposed and uncovered struts in both treatment groups and no correlation with on treatment LDL-C. This represents a reassuring finding with respect to the safety of DES in patients receiving intensive lipid lowering therapy. In contrast to our findings, a previous observational OCT study in South Korea investigating the effect of on treatment LDL-C level on neointimal hyperplasia among 218 patients treated with DES has demonstrated that neointimal tissue growth from 6 to 18 months was more suppressed in patients with a lower LDL-C level (58 ± 11 mg/dL) compared with those with a higher LDL-C level (92 ± 18 mg/dL) (change in neointimal area: 0.2 vs. 0.4mm 2 , p = 0.01) [ 26 ]. The potential reasons for inconsistent results include the observational versus randomized controlled design and the study duration. Limitations The present study has several limitations. First, the lack of significant differences between groups may be attributable to the lack of power (i.e., type II error) due to small sample size and low frequency of neoatherosclerosis. Second, OCT imaging for the culprit stents was not performed in all patients enrolled into the PACMAN-AMI trial, which may lead to patient selection bias. However, no differences in key baseline characteristics between patients with and without OCT imaging at 1 year were observed ( Supplementary Table 1 ). Third, the follow-up period of 1 year was relatively short to evaluate the occurrence of neoatherosclerosis, which can emerge consistently after 1 year and is the primary mechanism of very late (> 1 year) stent failure. Fourth, OCT findings at baseline including plaque morphology of the culprit lesion and acute stent results (i.e. stent expansion, strut apposition), known predictors of stent healing and neoatherosclerosis formation, were not available in the current study [ 19 ]. Fifth, although all patients were treated with current generation DES in the current study, the choice of stent type was left at the operator’s discretion. Stent type was reported in Supplementary Table 6 . Previous studies have reported that stent type was significantly associated with the occurrence of neoatherosclerosis [ 10 , 27 – 29 ]. Sixth, despite its high spatial resolution, OCT cannot reliably distinguish healthy neointima from fibrin and thrombus [ 30 ]. Conclusion Among AMI patients undergoing PCI of the culprit lesion with newer generation DES, there was no significant impact of alirocumab on the frequency of neoatherosclerosis and vessel healing at 1 year. The observed numerical difference and the finding of more stable neoatheroma in favor of alirocumab require further investigation in larger studies with extended follow-up. Statements & Declarations Acknowledgments The authors thank the staff personnel of the cardiovascular department at participating sites for their invaluable support. Conflict of interest Dr. Kakizaki reported receiving consulting fee from Infraredx USA, speaker fee from Abbott Medical Japan, Boston Scientific Japan, Philips Japan, Orbusneich Medical, manuscript writing fee from Orbusneich Medical and Philips Japan, Support for attending meetings and travel from OM Pharma outside the submitted work. Dr. Ueki reported receiving grants from Astellas Pharma, personal fees from Abbott Vascular, Amgen, Bayer, Daiichi Sankyo, Kowa, NIPRO, and Novartis, outside the submitted work. Dr. Koskinas reported receiving grants from Sanofi, Regeneron, and Infraredx during the conduct of the study and personal fees from Amgen and Daiichi Sankyo outside the submitted work. No other disclosures were reported. Dr. Losdat is employed by the DCR Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. (for an up-to-date list of DCR Bern’s conflicts of interest, see https://dcr.unibe.ch/services/terms__conditions/index_eng.html) Dr. Biccirè reported receiving consulting fee from Abbott, speaker fee from Abbott, Ultragenyx, and Sanofi outside the submitted work. Dr. Otsuka reported receiving speaker fees from Amgen, Nipro, and Kowa. Dr. Lønborg reported receiving grants from Boston Scientific, consulting fees from Boston Scientific, speakers fee from Abbott and Boston Scientific, and Support for attending meetings and travel from Abbott, and owns stock in Novo Nordisk. Dr. Kaiser reported receiving consulting fees from Unimedtec Switzerland and Swiss office of federal health. Dr. Iglesias reported receiving grants from Biotronik, Concept Medical, and Terumo, consulting fees from Medtronic, Biotronik, Cordis, and ReCor Medical, speakers fees from Medtronic, Penumbra, Biotronik, Concept Medical, BRISTOL MYERS SQUIBB/PFIZER, Cordis, and Recor Medical, Support for attending meetings and travel from Biotronik, and participating Data Safety Monitoring Board of the CoSTAR trial (NCT04870424). Dr. Spirk reported receiving personal fees from Sanofi-Aventis (Switzerland) at the time of study conduct and Cook Medical outside the submitted work. Dr. Daemen reported receiving institutional grant/research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Pie Medical, and ReCor medical, and consultancy and speaker fees from Abbott Vascular, Abiomed, ACIST medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, ReCor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care and Medtronic. Dr Engstrøm reported advisory board fees from Abbott and Novo Nordisk and speaker fees from Boston Scientific outside the submitted work. Dr. Lang has relationships with drug companies including AOP-Health, Actelion-Janssen, MSD, United Therapeutics, Pulnovo, Medtronic, INARI, Neutrolis and Sanofi. In addition to being investigator in trials involving these companies, relationships include consultancy service, research grants, and membership of scientific advisory boards. Dr. Räber reported receiving grants from Sanofi, Regeneron, and Infraredx to Inselspital and speaker fees from Sanofi during the conduct of the study and grants from Abbott, Heartflow, Boston Scientific, and Biotronik to Inselspital and grants from Abbott, Amgen, AstraZeneca, Occlutech, Sanofi, Canon, and Medtronic for speaker and consultation fees outside the submitted work. Funding The main PACMAN-AMI trial was funded by Sanofi, Regeneron, and Infraredx. Regeneron provided alirocumab and placebo free of charge. The current sub-study was conducted in an independent academic setting and funded by intramural grants of Bern University Hospital. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Ryota Kakizaki, Yasushi Ueki, Hiroki Shibutani, Flavio G. Biccirè, Tatsuhiko Otsuka, Jonas D. Häner, Jacob Lønborg, Christoph Kaiser, Juan F. Iglesias, Anna S. Ondracek, David Spirk, George C. M. Siontis, Joost Daemen, Thomas Engstrøm, Irene M. Lang, and Lorenz Räber. Statistical analysis was done by Sylvain Losdat. The first draft of the manuscript was written by Ryota Kakizaki, Yasushi Ueki, and Konstantinos C. Koskinas. All authors commented on previous versions of the manuscript, and all read and approved the final version. Lorenz Räber was responsible for supervision, conceptualization, and project administration. Ethics approval This study was performed in line with the principles of the Declaration of Helsinki, and the study was approved by the ethical committee at each site. Consent to participate Informed consent was obtained from all individual participants included in the study, all patients provided written informed consent. Consent to publish All participants provided informed consent, acknowledging that their health-related and personal information (and samples) would be shared only in encrypted form for research purposes, including international collaboration, and that their names would not be published in any form. Data availability statement The data set will be available from the corresponding author on reasonable request. References Piccolo R, Bonaa KH, Efthimiou O, Varenne O, Baldo A, et al. Drug-eluting or bare-metal stents for percutaneous coronary intervention: a systematic review and individual patient data meta-analysis of randomised clinical trials. Lancet . Jun 22 2019;393(10190):2503-2510. doi:10.1016/S0140-6736(19)30474-X Lee JM, Park KW, Han JK, Yang HM, Kang HJ, et al. Three-year patient-related and stent-related outcomes of second-generation everolimus-eluting Xience V stents versus zotarolimus-eluting resolute stents in real-world practice (from the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries). Am J Cardiol . Nov 1 2014;114(9):1329-38. doi:10.1016/j.amjcard.2014.07.065 Camenzind E, Wijns W, Mauri L, Kurowski V, Parikh K, et al. Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial. Lancet . Oct 20 2012;380(9851):1396-405. doi:10.1016/S0140-6736(12)61336-1 Zanchin C, Ueki Y, Zanchin T, Haner J, Otsuka T, et al. Everolimus-Eluting Biodegradable Polymer Versus Everolimus-Eluting Durable Polymer Stent for Coronary Revascularization in Routine Clinical Practice. JACC Cardiovasc Interv . Sep 9 2019;12(17):1665-1675. doi:10.1016/j.jcin.2019.04.046 Takano M, Yamamoto M, Inami S, Murakami D, Ohba T, et al. Appearance of lipid-laden intima and neovascularization after implantation of bare-metal stents extended late-phase observation by intracoronary optical coherence tomography. J Am Coll Cardiol . Dec 29 2009;55(1):26-32. doi:10.1016/j.jacc.2009.08.032 Taniwaki M, Radu MD, Zaugg S, Amabile N, Garcia-Garcia HM, et al. Mechanisms of Very Late Drug-Eluting Stent Thrombosis Assessed by Optical Coherence Tomography. Circulation . Feb 16 2016;133(7):650-60. doi:10.1161/CIRCULATIONAHA.115.019071 Nakamura D, Attizzani GF, Toma C, Sheth T, Wang W, et al. Failure Mechanisms and Neoatherosclerosis Patterns in Very Late Drug-Eluting and Bare-Metal Stent Thrombosis. Circ Cardiovasc Interv . Sep 2016;9(9)doi:10.1161/CIRCINTERVENTIONS.116.003785 Kawai K, Virmani R, Finn AV. In-Stent Restenosis. Interv Cardiol Clin . Oct 2022;11(4):429-443. doi:10.1016/j.iccl.2022.02.005 Nakazawa G, Finn AV, Joner M, Ladich E, Kutys R, et al. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study. Circulation . Sep 9 2008;118(11):1138-45. doi:10.1161/CIRCULATIONAHA.107.762047 Kuroda M, Otake H, Shinke T, Takaya T, Nakagawa M, et al. The impact of in-stent neoatherosclerosis on long-term clinical outcomes: an observational study from the Kobe University Hospital optical coherence tomography registry. EuroIntervention . Dec 10 2016;12(11):e1366-e1374. doi:10.4244/EIJY15M12_05 Chen Z, Matsumura M, Mintz GS, Noguchi M, Fujimura T, et al. Prevalence and Impact of Neoatherosclerosis on Clinical Outcomes After Percutaneous Treatment of Second-Generation Drug-Eluting Stent Restenosis. Circ Cardiovasc Interv . Sep 2022;15(9):e011693. doi:10.1161/CIRCINTERVENTIONS.121.011693 Shimono H, Kajiya T, Takaoka J, Miyamura A, Inoue T, et al. Characteristics of recurrent in-stent restenosis after second- and third-generation drug-eluting stent implantation. Coron Artery Dis . Jan 2021;32(1):36-41. doi:10.1097/MCA.0000000000000945 Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med . Nov 29 2018;379(22):2097-2107. doi:10.1056/NEJMoa1801174 Raber L, Ueki Y, Otsuka T, Losdat S, Haner JD, et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA . May 10 2022;327(18):1771-1781. doi:10.1001/jama.2022.5218 Zanchin C, Koskinas KC, Ueki Y, Losdat S, Haner JD, et al. Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-Rationale and design of the PACMAN-AMI trial. Am Heart J . Aug 2021;238:33-44. doi:10.1016/j.ahj.2021.04.006 Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J . Oct 12 2023;44(38):3720-3826. doi:10.1093/eurheartj/ehad191 Guagliumi G, Shimamura K, Sirbu V, Garbo R, Boccuzzi G, et al. Temporal course of vascular healing and neoatherosclerosis after implantation of durable- or biodegradable-polymer drug-eluting stents. Eur Heart J . Jul 7 2018;39(26):2448-2456. doi:10.1093/eurheartj/ehy273 Tearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol . Mar 20 2012;59(12):1058-72. doi:10.1016/j.jacc.2011.09.079 Hoshino M, Yonetsu T, Kanaji Y, Usui E, Yamaguchi M, et al. Impact of baseline plaque characteristic on the development of neoatherosclerosis in the very late phase after stenting. J Cardiol . Jul 2019;74(1):67-73. doi:10.1016/j.jjcc.2019.01.002 Nagano Y, Otake H, Toba T, Kuroda K, Shinkura Y, et al. Impaired Cholesterol-Uptake Capacity of HDL Might Promote Target-Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation. J Am Heart Assoc . May 7 2019;8(9):e011975. doi:10.1161/JAHA.119.011975 Niccoli G, Dato I, Imaeva AE, Antonazzo Panico R, Roberto M, et al. Association between inflammatory biomarkers and in-stent restenosis tissue features: an Optical Coherence Tomography Study. Eur Heart J Cardiovasc Imaging . Aug 2014;15(8):917-25. doi:10.1093/ehjci/jeu035 Cao YX, Li S, Liu HH, Li JJ. Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials. BMJ Open . Oct 4 2018;8(9):e022348. doi:10.1136/bmjopen-2018-022348 Taniwaki M, Windecker S, Zaugg S, Stefanini GG, Baumgartner S, et al. The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study. Eur Heart J . Aug 21 2015;36(32):2167-76. doi:10.1093/eurheartj/ehv227 Sakai R, Sekimoto T, Koba S, Mori H, Matsukawa N, et al. Impact of triglyceride-rich lipoproteins on early in-stent neoatherosclerosis formation in patients undergoing statin treatment. J Clin Lipidol . Mar-Apr 2023;17(2):281-290. doi:10.1016/j.jacl.2023.01.004 Taniwaki M, Haner JD, Kakizaki R, Ohno Y, Yahagi K, et al. Long-term effect of biodegradable vs durable polymer everolimus-eluting stents on neoatherosclerosis in ST-segment elevation myocardial infarction: the CONNECT trial. Eur Heart J . Sep 1 2024;doi:10.1093/eurheartj/ehae589 Jang JY, Kim JS, Shin DH, Kim BK, Ko YG, et al. Favorable effect of optimal lipid-lowering therapy on neointimal tissue characteristics after drug-eluting stent implantation: qualitative optical coherence tomographic analysis. Atherosclerosis . Oct 2015;242(2):553-9. doi:10.1016/j.atherosclerosis.2015.08.014 Yonetsu T, Kim JS, Kato K, Kim SJ, Xing L, et al. Comparison of incidence and time course of neoatherosclerosis between bare metal stents and drug-eluting stents using optical coherence tomography. Am J Cardiol . Oct 1 2012;110(7):933-9. doi:10.1016/j.amjcard.2012.05.027 Song L, Mintz GS, Yin D, Yamamoto MH, Chin CY, et al. Neoatherosclerosis assessed with optical coherence tomography in restenotic bare metal and first- and second-generation drug-eluting stents. Int J Cardiovasc Imaging . Aug 2017;33(8):1115-1124. doi:10.1007/s10554-017-1106-2 Lee SY, Hur SH, Lee SG, Kim SW, Shin DH, et al. Optical coherence tomographic observation of in-stent neoatherosclerosis in lesions with more than 50% neointimal area stenosis after second-generation drug-eluting stent implantation. Circ Cardiovasc Interv . Feb 2015;8(2):e001878. doi:10.1161/CIRCINTERVENTIONS.114.001878 Jinnouchi H, Otsuka F, Sato Y, Bhoite RR, Sakamoto A, et al. Healthy Strut Coverage After Coronary Stent Implantation: An Ex Vivo Human Autopsy Study. Circ Cardiovasc Interv . May 2020;13(5):e008869. doi:10.1161/CIRCINTERVENTIONS.119.008869 Additional Declarations Competing interest reported. Dr. Kakizaki reported receiving consulting fee from Infraredx USA, speaker fee from Abbott Medical Japan, Boston Scientific Japan, Philips Japan, Orbusneich Medical, manuscript writing fee from Orbusneich Medical and Philips Japan, Support for attending meetings and travel from OM Pharma outside the submitted work. Dr. Ueki reported receiving grants from Astellas Pharma, personal fees from Abbott Vascular, Amgen, Bayer, Daiichi Sankyo, Kowa, NIPRO, and Novartis, outside the submitted work. Dr. Koskinas reported receiving grants from Sanofi, Regeneron, and Infraredx during the conduct of the study and personal fees from Amgen and Daiichi Sankyo outside the submitted work. No other disclosures were reported. Dr. Losdat is employed by the DCR Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. (for an up-to-date list of DCR Bern’s conflicts of interest, see https://dcr.unibe.ch/services/terms__conditions/index_eng.html ) Dr. Biccirè reported receiving consulting fee from Abbott, speaker fee from Abbott, Ultragenyx, and Sanofi outside the submitted work. Dr. Otsuka reported receiving speaker fees from Amgen, Nipro, and Kowa. Dr. Lønborg reported receiving grants from Boston Scientific, consulting fees from Boston Scientific, speakers fee from Abbott and Boston Scientific, and Support for attending meetings and travel from Abbott, and owns stock in Novo Nordisk. Dr. Kaiser reported receiving consulting fees from Unimedtec Switzerland and Swiss office of federal health. Dr. Iglesias reported receiving grants from Biotronik, Concept Medical, and Terumo, consulting fees from Medtronic, Biotronik, Cordis, and ReCor Medical, speakers fees from Medtronic, Penumbra, Biotronik, Concept Medical, BRISTOL MYERS SQUIBB/PFIZER, Cordis, and Recor Medical, Support for attending meetings and travel from Biotronik, and participating Data Safety Monitoring Board of the CoSTAR trial (NCT04870424). Dr. Spirk reported receiving personal fees from Sanofi-Aventis (Switzerland) at the time of study conduct and Cook Medical outside the submitted work. Dr. Daemen reported receiving institutional grant/research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Pie Medical, and ReCor medical, and consultancy and speaker fees from Abbott Vascular, Abiomed, ACIST medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, ReCor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care and Medtronic. Dr Engstrøm reported advisory board fees from Abbott and Novo Nordisk and speaker fees from Boston Scientific outside the submitted work. Dr. Lang has relationships with drug companies including AOP-Health, Actelion-Janssen, MSD, United Therapeutics, Pulnovo, Medtronic, INARI, Neutrolis and Sanofi. In addition to being investigator in trials involving these companies, relationships include consultancy service, research grants, and membership of scientific advisory boards. Dr. Räber reported receiving grants from Sanofi, Regeneron, and Infraredx to Inselspital and speaker fees from Sanofi during the conduct of the study and grants from Abbott, Heartflow, Boston Scientific, and Biotronik to Inselspital and grants from Abbott, Amgen, AstraZeneca, Occlutech, Sanofi, Canon, and Medtronic for speaker and consultation fees outside the submitted work. Supplementary Files Supplementaryfile.docx GraphicalAbstract.png Graphic abstract Alirocumab was associated with a numerically favourable, though not statistically significant, reduction in neoatherosclerosis at 1 year in AMI culprit lesions treated with newer-generation DES. Cite Share Download PDF Status: Published Journal Publication published 18 Aug, 2025 Read the published version in The International Journal of Cardiovascular Imaging → Version 1 posted Editorial decision: Revision requested 08 Jun, 2025 Reviews received at journal 01 Jun, 2025 Reviews received at journal 28 May, 2025 Reviews received at journal 21 May, 2025 Reviewers agreed at journal 17 May, 2025 Reviewers agreed at journal 17 May, 2025 Reviewers agreed at journal 07 May, 2025 Reviewers invited by journal 07 May, 2025 Editor assigned by journal 05 May, 2025 Submission checks completed at journal 05 May, 2025 First submitted to journal 05 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Bubble size is proportional to the overall number of patients (PACMAN-AMI alirocumab group: 95, PACMAN-AMI Placebo group: 96, CONNECT BP-EES group: 88, CONNECT DP-EES group: 90, TRANSFORM-OCT BP-EES group: 43, TRANSFORM-OCT DP-ZES group: 44, Sakai_J Clin Lipidol 2023: 114).\u003c/p\u003e\n\u003cp\u003eBP: biodegradable polymer, DP: durable polymer, EES: everolimus-eluting stents, LDL-C: low density lipoprotein cholesterol, ZES: zotarolimus-eluting stents\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6592491/v1/9dbf34128566149b269fa388.png"},{"id":82619726,"identity":"20debbea-469c-4576-87dd-8a7a393e516d","added_by":"auto","created_at":"2025-05-13 12:10:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1260059,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6592491/v1/6fe13154-ae3f-4d19-b0fc-9f1e45450cc7.pdf"},{"id":82616727,"identity":"8edee7f6-434c-4c08-92da-2eb66bfafd15","added_by":"auto","created_at":"2025-05-13 11:46:18","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":323504,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile.docx","url":"https://assets-eu.researchsquare.com/files/rs-6592491/v1/c3268f1272056df51a4f1fdc.docx"},{"id":82616720,"identity":"9f0f7899-5669-4a1a-9f25-aedc8bb8cee8","added_by":"auto","created_at":"2025-05-13 11:46:18","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":233227,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraphic abstract\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlirocumab was associated with a numerically favourable, though not statistically significant, reduction in neoatherosclerosis at 1 year in AMI culprit lesions treated with newer-generation DES.\u003c/p\u003e","description":"","filename":"GraphicalAbstract.png","url":"https://assets-eu.researchsquare.com/files/rs-6592491/v1/6dac72c194489cbd09325052.png"}],"financialInterests":"Competing interest reported. Dr. Kakizaki reported receiving consulting fee from Infraredx USA, speaker fee from Abbott Medical Japan, Boston Scientific Japan, Philips Japan, Orbusneich Medical, manuscript writing fee from Orbusneich Medical and Philips Japan, Support for attending meetings and travel from OM Pharma outside the submitted work. Dr. Ueki reported receiving grants from Astellas Pharma, personal fees from Abbott Vascular, Amgen, Bayer, Daiichi Sankyo, Kowa, NIPRO, and Novartis, outside the submitted work. Dr. Koskinas reported receiving grants from Sanofi, Regeneron, and Infraredx during the conduct of the study and personal fees from Amgen and Daiichi Sankyo outside the submitted work. No other disclosures were reported. Dr. Losdat is employed by the DCR Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. (for an up-to-date list of DCR Bern’s conflicts of interest, see https://dcr.unibe.ch/services/terms__conditions/index_eng.html) Dr. Biccirè reported receiving consulting fee from Abbott, speaker fee from Abbott, Ultragenyx, and Sanofi outside the submitted work. Dr. Otsuka reported receiving speaker fees from Amgen, Nipro, and Kowa. Dr. Lønborg reported receiving grants from Boston Scientific, consulting fees from Boston Scientific, speakers fee from Abbott and Boston Scientific, and Support for attending meetings and travel from Abbott, and owns stock in Novo Nordisk. Dr. Kaiser reported receiving consulting fees from Unimedtec Switzerland and Swiss office of federal health. Dr. Iglesias reported receiving grants from Biotronik, Concept Medical, and Terumo, consulting fees from Medtronic, Biotronik, Cordis, and ReCor Medical, speakers fees from Medtronic, Penumbra, Biotronik, Concept Medical, BRISTOL MYERS SQUIBB/PFIZER, Cordis, and Recor Medical, Support for attending meetings and travel from Biotronik, and participating Data Safety Monitoring Board of the CoSTAR trial (NCT04870424). Dr. Spirk reported receiving personal fees from Sanofi-Aventis (Switzerland) at the time of study conduct and Cook Medical outside the submitted work. Dr. Daemen reported receiving institutional grant/research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Pie Medical, and ReCor medical, and consultancy and speaker fees from Abbott Vascular, Abiomed, ACIST medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, ReCor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care and Medtronic. Dr Engstrøm reported advisory board fees from Abbott and Novo Nordisk and speaker fees from Boston Scientific outside the submitted work. Dr. Lang has relationships with drug companies including AOP-Health, Actelion-Janssen, MSD, United Therapeutics, Pulnovo, Medtronic, INARI, Neutrolis and Sanofi. In addition to being investigator in trials involving these companies, relationships include consultancy service, research grants, and membership of scientific advisory boards. Dr. Räber reported receiving grants from Sanofi, Regeneron, and Infraredx to Inselspital and speaker fees from Sanofi during the conduct of the study and grants from Abbott, Heartflow, Boston Scientific, and Biotronik to Inselspital and grants from Abbott, Amgen, AstraZeneca, Occlutech, Sanofi, Canon, and Medtronic for speaker and consultation fees outside the submitted work.","formattedTitle":"Impact of Alirocumab on Neoatherosclerosis Formation and Vessel Healing after Drug-eluting Stent Implantation in Patients with Acute Myocardial Infarction: a Substudy of the PACMAN-AMI Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDrug-eluting stents (DES) have improved the overall safety and efficacy of percutaneous coronary intervention (PCI) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, late stent failures including in-stent restenosis and stent thrombosis continue to occur at relatively low, but constant rates [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Neoatherosclerosis, histologically characterized by the accumulation of lipid-laden macrophage foam cells, necrotic core, and calcification in the neointimal tissue of the stented segment [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], is increasingly recognized as a major pathophysiological mechanism underlying late stent failures [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In culprit lesions of acute myocardial infarction (AMI), delayed vessel healing, characterized by less neointimal thickness, higher prevalence of uncovered struts, and greater inflammation, leads to more severe endothelial dysfunction and impaired endothelial barrier, potentially resulting in an accelerated formation of neoatherosclerosis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough procedure-related factors including stent type (i.e. strut thickness, polymer type), strut apposition, and underlying plaque type are important substrates for neoatherosclerosis formation and vessel healing following DES implantation, previous studies have consistently demonstrated a significant positive association between serum low-density lipoprotein cholesterol (LDL-C) levels and the occurrence of neoatherosclerosis [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) added to statins potently reduce LDL-C and thereby result in significant plaque regression and cardiovascular benefits compared with statin therapy alone [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. To date, the effect of intensive lipid-lowering therapy with PCSK9i on top of high-intensity statin on neoatherosclerosis formation and late stent healing remains to be elucidated.\u003c/p\u003e \u003cp\u003eTherefore, we have performed a predefined substudy of the randomized, double-blind PACMAN-AMI (effects of the PSCK9 antibody AliroCuMab on coronary Atherosclerosis in patieNtswith Acute Myocardial Infarction) trial to assess whether intensive lipid-lowering therapy with alirocumab impacts on the frequency of neoatherosclerosis and vessel healing.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThe PACMAN-AMI trial (NCT03067844) was an investigator-initiated, multicenter, randomized, double-blind clinical trial conducted at 9 centers in 4 European countries (Switzerland, Austria, Denmark, and the Netherlands). The study design and main results of the PACMAN-AMI trial has been reported previously [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In brief, the PACMAN-AMI trial included 300 patients with 18 years or older who underwent PCI of the culprit lesion for treatment of ST-elevation or non-ST-elevation myocardial infarction. Patients were randomized to receive biweekly alirocumab or placebo for 52 weeks in addition to high-intensity statin therapy (rosuvastatin 20 mg). The present pre-specified substudy included patients who underwent optical coherence tomography (OCT) imaging for the culprit lesion of AMI at 52 weeks following primary PCI. OCT recording was performed if the operator deemed it feasible for the culprit lesion at one year follow-up. PCI was performed in accordance with the European Society of Cardiology Guidelines [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and DES selection was at the discretion of the operator. All patients provided written informed consent, and the study was approved by the ethical committee at each site.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAcquisition and Analysis of Intracoronary Imaging\u003c/h3\u003e\n\u003cp\u003eThe OCT imaging was performed using a frequency-domain OCT system (Dragon Fly, LightLab, St. Jude Medical, St. Paul, MN, USA). OCT images were analyzed at independent core laboratory (Bern University Hospital, Bern, Switzerland) by experienced analysts. Cross-sectional OCT images were evaluated quantitatively and qualitatively with an interval of 0.4 mm within the stented segments using proprietary software (QCU-CMS version 4.69 software, LKEB, Leiden, The Netherlands). Neointima was defined as the tissue between the luminal border and the endoluminal border of the struts. Neoatherosclerosis was defined as either the presence of lipid-laden neointima or calcification with a longitudinal extension of \u0026ge;\u0026thinsp;1.2 mm, the presence of macrophage, or the presence of cholesterol crystals [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Fibroatheroma were characterized as a signal-poor region displaying high attenuation (to differentiate from layered neointima) with diffuse borders and a lateral extension of at least one quadrant [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Calcification were defined as signal-poor regions with low attenuation and clear borderlines. Macrophage was defined as lines or dots with strong signal attenuation producing a shadow with a sharply delineated lateral border. In-stent cholesterol crystal was defined as thin and linear structures with high backscattering without attenuation within the neointima. Stent strut coverage and malapposition were defined and measured as described previously [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eStudy endpoints\u003c/h3\u003e\n\u003cp\u003ePrimary endpoint was the frequency of neoatherosclerosis at 1 year, and key secondary endpoints were neointimal area, neointimal thickness, and percentage of uncovered and malapposed struts at 1 year.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were summarized as mean (standard deviation) or median [interquartile range]. Between-group comparisons were conducted using Student t-tests or Wilcoxon-Mann-Whitney tests, as appropriate. Categorical variables were summarized as counts (percentage) and compared between groups using Fisher\u0026rsquo;s exact tests. Statistical significance was set to 0.05. All statistical analyses were performed using Stata 17 (StataCorp LLC, College Station, TX) and R 4.4.1 (R Core Team).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eBaseline and procedural characteristics\u003c/h2\u003e \u003cp\u003eA total of 191 patients (95 in the alirocumab group and 96 in the placebo group) undergoing OCT imaging for the culprit stents at 1 year were analyzed for the current sub-study (\u003cb\u003eSupplementary Fig.\u0026nbsp;1\u003c/b\u003e). Baseline clinical and procedural characteristics were well-balanced between treatment groups (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There were no significant differences in baseline characteristics between patients with and without OCT for the culprit lesion at 1 year follow-up, except for the frequency of dyslipidemia and P2Y12 inhibitor at baseline (\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e). LDL-C level at follow-up was 23.2\u0026thinsp;\u0026plusmn;\u0026thinsp;23.2 mg/dL in the alirocumab group and 73.5\u0026thinsp;\u0026plusmn;\u0026thinsp;30.9 mg/dL in the placebo group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics and medication\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;191\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAlirocumab\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;95\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;96\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58.1 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.9 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.4 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMen, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e160 (83.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83 (87.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77 (80.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.9 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.4 ( 4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical history, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArterial hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81 (42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (35.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (49.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyslipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e162 (84.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79 (83.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83 (86.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87 (45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (39.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious myocardial infarction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious PCI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral arterial disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of CAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (30.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (29.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of acute myocardial infarction, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNSTEMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85 (44.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (47.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTEMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106 (55.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56 (58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak CK, IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e687 (1061)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e770 (1191)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e605 (915)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeak hs-cTnT, ng/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1189 (2734)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1417 (3311)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e961 (1991)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStatin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-intensity statin therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEzetimibe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiplatelet therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP2Y12 inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-coagulant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-Blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACEI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eARB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eValues are count (percentage) or mean (SD). Abbreviations: ACEI: angiotensin converting enzyme inhibitor, ARB: angiotensin receptor blocker, BMI: body mass index, CAD: coronary artery disease, CK: creatinine kinase, cTnT: cardiac troponin T, LVEF: left ventricular ejection fraction, NSTEMI: non-ST-segment elevation myocardial infarction, PCI: percutaneous coronary intervention, STEMI: ST-segment elevation myocardial infarction\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLesion and procedure characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;191\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAlirocumab\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;95\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;96\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTarget vessel location, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft anterior descending\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (48.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (49.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (47.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft circumflex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight coronary artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (29.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (34.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFinal TIMI flow, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e190 (99.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94 (98.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of stents, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0 [0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0 [0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0 [0.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal stent length, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.0 [20.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.0 [20.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.0 [17.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStent diameter, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5 [1.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5 [1.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5 [1.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolymer type, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiodegradable polymer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98 (51.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (51.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDurable polymer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (45.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (47.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-dilatation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e160 (83.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (82.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82 (85.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBifurcation lesion, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultivessel PCI, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGP IIb/IIIa inhibitors, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (16.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eValues are count (percentage), mean (SD), or median [interquartile range]. Multivessel treatment and GP IIb/IIIa are at patient level. All other variables refer to the culprit lesion. Abbreviations: GP: glycoprotein, PCI: percutaneous coronary intervention, TIMI: thrombolysis in myocardial infarction\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOCT findings\u003c/h3\u003e\n\u003cp\u003eOCT findings are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Neoatherosclerosis was observed in 13 (6.8%) patients, 4 (4.2%) in the alirocumab group and 9 (9.4%) in the placebo group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.25). The frequency of fibroatheroma, fibrocalcific plaque, macrophage, and cholesterol crystal was 5.8%, 1.0%, 1.0%, and 2.1%, respectively, without statistical differences between treatment groups. Among 11 patients with lipid-laden neointima, fibrous cap thickness was significantly greater in the alirocumab group than in the placebo group (217\u0026thinsp;\u0026plusmn;\u0026thinsp;123 \u0026micro;m vs. 88\u0026thinsp;\u0026plusmn;\u0026thinsp;49 \u0026micro;m, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). The characteristics of patients with neoatherosclerosis were summarized in \u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e. Biochemical measures and intracoronary imaging findings in patients with and without neoatherosclerosis were shown in \u003cb\u003eSupplementary Table\u0026nbsp;3\u003c/b\u003e. Absolute change in serum LDL-C level was \u0026minus;\u0026thinsp;106.5 (-135.4 to -77.5) vs. -104.3 (-111.0 to -97.6) mg/dL in patients with vs. without neoatherosclerosis. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the correlation between frequency of neoatherosclerosis and LDL-C level in prospective studies.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOCT analysis at 1 year\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;191\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAlirocumab\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;95\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;96\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration from implantation, day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e376 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e377 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e374 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoatherosclerosis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibroatheroma, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e*Total length of fibroatheroma, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.78 (4.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.00 (3.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.80 (5.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e*Maximum lipid arc, degree\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e173 (73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e155 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e184 (89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e*Minimum cap thickness, \u0026micro;m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e135 (101)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e217 (123)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88 (49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrocalcified, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrophage accumulations, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIn-stent cholesterol crystal, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther findings, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrovessel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (41.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLesion level analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnalyzed stent length, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.1 (14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.1 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.0 (14.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimal lumen area, mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.82 (2.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.09 (2.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.55 (2.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimal stent area, mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.05 (2.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.21 (2.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.90 (2.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCross section level analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnalyzed cross section per lesion, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean lumen area, mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.98 (2.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.13 (2.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.83 (2.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean stent area, mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.06 (2.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.12 (2.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.00 (3.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeointimal area, mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.14 (0.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.07 (0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.20 (0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalapposed area, mm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05 (0.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07 (0.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03 (0.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStrut level analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnalyzed struts per lesion, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e762 (364)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e744 (353)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e781 (375)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean neointimal thickness, \u0026micro;m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145 (88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e151 (101)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRate of uncovered struts, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.7 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.3 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRate of malapposed struts, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.7 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncomplete apposition distance, \u0026micro;m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.66 (12.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.73 (13.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.61 (9.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eValues are count (percentage) or mean (SD). Abbreviations: OCT: optical coherence tomography. *calculated across 11 patients.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAt a cross sectional level, there were no differences in the frequency of cross sections with uncovered struts (15.0 vs. 12.13%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.57) and malapposed struts (4.0 vs. 1.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.24), and neointimal area (1.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73 vs. 1.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96 mm\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.60) between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). \u003cb\u003eSupplementary Fig.\u0026nbsp;2\u003c/b\u003e shows the correlation between neointimal area and absolute change in LDL-C, and \u003cb\u003eSupplementary Fig.\u0026nbsp;3\u003c/b\u003e shows the correlation between percentage of uncovered struts and absolute change in LDL-C. At a strut level, the percentage of uncovered struts (3.1 vs. 2.3%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.45), the percentage of malapposed struts (0.9 vs. 0.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.27) and neointimal thickness (136 vs. 151 \u0026micro;m, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.45) were comparable between two groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Patients with neoatherosclerosis had greater neointimal area (2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08 vs. 1.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79 mm\u003csup\u003e2\u003c/sup\u003e) and greater neointimal thickness (241\u0026thinsp;\u0026plusmn;\u0026thinsp;97 vs. 137\u0026thinsp;\u0026plusmn;\u0026thinsp;83 \u0026micro;m) compared with those without (\u003cb\u003eSupplementary Table\u0026nbsp;4\u003c/b\u003e).\u003c/p\u003e\n\u003ch3\u003eClinical outcomes\u003c/h3\u003e\n\u003cp\u003e \u003cb\u003eSupplementary Table\u0026nbsp;5\u003c/b\u003e shows the incidence of the revascularization at 1 year. Revascularization was performed in 35 patients (18.3%). Among them, 11 patients (5.8%) underwent ischemia-driven target lesion revascularization, 2 (15.4%) with neoatherosclerosis and 9 (5.1%) without neoatherosclerosis. Ischemia-driven non-target lesion revascularization was performed in 19 patients (9.9%), 1 (7.7%) in patients with neoatherosclerosis and 18 (10.1%) in patients without neoatherosclerosis.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the first study to investigate the effect of very low LDL-C level achieved by alirocumab on neoatherosclerosis formation and vessel healing among AMI patients undergoing PCI with current generation DES. The main findings of the present study, based on OCT performed in the stented culprit lesion 1 year after primary PCI, are: (1) there were no significant differences in the frequency of neoatherosclerosis between the alirocumab and placebo groups in the context of a background high-intensity statin treatment in both treatment arms (rosuvastatin 20 mg). However, neoatheroma in the alirocumab group was more stable as suggested by a significantly greater minimal fibrous cap thickness, (2) the degree of vessel healing represented by neointimal growth, strut coverage, and strut apposition did not significantly differ between the treatment groups at 1 year following primary PCI.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eFrequency of neoatherosclerosis\u003c/h2\u003e \u003cp\u003eAlthough there are several relevant differences in pathogenic mechanisms between in-stent neoatherosclerosis and native atherosclerosis, lipid diffusion and inflammatory cell migration through the endothelium are considered common pathways of atherosclerosis formation for both disease entities. Previous retrospective observational studies have demonstrated a significant correlation between the serum LDL-C level and the frequency of neoatherosclerosis [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In the current study, the frequency of neoatherosclerosis was numerically lower in the alirocumab group (4.2% vs. 9.4%), but there was no significant difference between groups despite very low LDL-C levels achieved in the alirocumab group (mean 23.2 mg/dL vs. 73.5 mg/dL). A potential explanation may be the lack of power (i.e. type II error) in view of only 13 patients with neoatherosclerosis at 1 year. The relatively short follow-up period of 1 year in our pre-specified sub-study may at least partly contribute to small number of neoatherosclerosis formation. Another explanation may be the initiation of high-intensity statin therapy (rosuvastatin 20 mg) in both groups from the first day after primary PCI, which was not the case in previous studies. Statins not only decrease LDL-C level but also reduce inflammation, which can lead to endothelial cell activation and dysfunction [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and thus result in neoatherosclerosis formation. The level of high sensitive C-reactive protein (hsCRP) was reportedly associated with the accumulation of lipids within the neointima [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Unlike statins, PSCK9i have little no effect on inflammation [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and accordingly, the on-treatment hsCRP level was similar in both treatment groups in our study (2.0 vs. 2.5 mg/L, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.71). Interestingly, neoatheroma in the alirocumab group had a significantly greater minimal fibrous cap thickness. This finding may suggest that intensive lipid-lowering afforded by alirocumab resulted in more stable neoatheroma, along the lines of the effects of alirocumab observed in the main study investigating native atherosclerosis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe frequency of neoatherosclerosis in the alirocumab group in the current study (4.2%) appeared to be among the lowest ever reported compared with previous prospective observational studies that typically found neoatherosclerosis in 11.4\u0026ndash;15.9% between 1\u0026ndash;3 years with on-treatment LDL-C levels between 63\u0026ndash;80 mg/dL [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Moreover, the frequency of neoatherosclerosis in the placebo group of the present study (9.4%) was also numerically lower compared to that reported in previous studies despite a similar on-treatment LDL-C level. The lower frequency in the current study may be explained by the routine use of high-intensity statin therapy, stent types, and clinical presentation. In particular, a previous pathological study reported that neointimal thickness in culprit site of AMI was significantly smaller than in coronary lesions in stable patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Given the pathological role of in-stent neointima as a basis for neoatherosclerosis formation, the lower frequency of neoatherosclerosis might be attributed to smaller neointimal tissue in the AMI culprit lesions in the current study.\u003c/p\u003e \u003cp\u003eInterestingly, we noted some patients with neoatherosclerosis formation within 12 months with very low on treatment LDL-C values (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), i.e. 3 patients with \u0026lt;\u0026thinsp;20mg/dL. This underlines that on-treatment LDL-C should not be considered as an isolated driver of neoatherosclerosis. In these patients, hsCRP levels at follow-up were 0, 0, and 0.8 mg/L, respectively. These three patients suggest that other, incompletely understood mechanisms unrelated to LDL-C and inflammation may come into play.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;191\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNeoatherosclerosis (+)\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;13\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNeoatherosclerosis (-)\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;178\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny revascularization n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e32 (18.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemia driven revascularization n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e27 (15.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemia driven target lesion revascularization n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e9 (5.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemia driven non-target lesion revascularization n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e18 (10.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eValues are count (percentage).\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eNeointimal growth and strut malapposition\u003c/h2\u003e \u003cp\u003eIn the current study, there was no significant difference in the degree of neointimal hyperplasia, strut coverage, and strut apposition. Although there have been potential concerns of late-acquired malapposition due to pronounced plaque regression induced by intensive LDL-C lowering with alirocumab, reassuringly, we did not observe such a phenomenon in the current analysis showing a low and similar frequency of malapposed and uncovered struts in both treatment groups and no correlation with on treatment LDL-C. This represents a reassuring finding with respect to the safety of DES in patients receiving intensive lipid lowering therapy.\u003c/p\u003e \u003cp\u003eIn contrast to our findings, a previous observational OCT study in South Korea investigating the effect of on treatment LDL-C level on neointimal hyperplasia among 218 patients treated with DES has demonstrated that neointimal tissue growth from 6 to 18 months was more suppressed in patients with a lower LDL-C level (58\u0026thinsp;\u0026plusmn;\u0026thinsp;11 mg/dL) compared with those with a higher LDL-C level (92\u0026thinsp;\u0026plusmn;\u0026thinsp;18 mg/dL) (change in neointimal area: 0.2 vs. 0.4mm\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The potential reasons for inconsistent results include the observational versus randomized controlled design and the study duration.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe present study has several limitations. First, the lack of significant differences between groups may be attributable to the lack of power (i.e., type II error) due to small sample size and low frequency of neoatherosclerosis. Second, OCT imaging for the culprit stents was not performed in all patients enrolled into the PACMAN-AMI trial, which may lead to patient selection bias. However, no differences in key baseline characteristics between patients with and without OCT imaging at 1 year were observed (\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e). Third, the follow-up period of 1 year was relatively short to evaluate the occurrence of neoatherosclerosis, which can emerge consistently after 1 year and is the primary mechanism of very late (\u0026gt;\u0026thinsp;1 year) stent failure. Fourth, OCT findings at baseline including plaque morphology of the culprit lesion and acute stent results (i.e. stent expansion, strut apposition), known predictors of stent healing and neoatherosclerosis formation, were not available in the current study [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Fifth, although all patients were treated with current generation DES in the current study, the choice of stent type was left at the operator\u0026rsquo;s discretion. Stent type was reported in \u003cb\u003eSupplementary Table\u0026nbsp;6\u003c/b\u003e. Previous studies have reported that stent type was significantly associated with the occurrence of neoatherosclerosis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Sixth, despite its high spatial resolution, OCT cannot reliably distinguish healthy neointima from fibrin and thrombus [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAmong AMI patients undergoing PCI of the culprit lesion with newer generation DES, there was no significant impact of alirocumab on the frequency of neoatherosclerosis and vessel healing at 1 year. The observed numerical difference and the finding of more stable neoatheroma in favor of alirocumab require further investigation in larger studies with extended follow-up.\u003c/p\u003e"},{"header":"Statements \u0026 Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the staff personnel of the cardiovascular department at participating sites for their invaluable support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Kakizaki reported receiving consulting fee from Infraredx USA, speaker fee from Abbott Medical Japan, Boston Scientific Japan, Philips Japan, Orbusneich Medical, manuscript writing fee from Orbusneich Medical and Philips Japan, Support for attending meetings and travel from OM Pharma outside the submitted work. Dr. Ueki reported receiving grants from Astellas Pharma, personal fees from Abbott Vascular, Amgen, Bayer, Daiichi Sankyo, Kowa, NIPRO, and Novartis, outside the submitted work. Dr. Koskinas reported receiving grants from Sanofi, Regeneron, and Infraredx during the conduct of the study and personal fees from Amgen and Daiichi Sankyo outside the submitted work. No other disclosures were reported. Dr. Losdat is employed by the DCR Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. (for an up-to-date list of DCR Bern\u0026rsquo;s conflicts of interest, see https://dcr.unibe.ch/services/terms__conditions/index_eng.html) Dr. Biccir\u0026egrave; reported receiving consulting fee from Abbott, speaker fee from Abbott, Ultragenyx, and Sanofi outside the submitted work. Dr. Otsuka reported receiving speaker fees from Amgen, Nipro, and Kowa. Dr. L\u0026oslash;nborg reported receiving grants from Boston Scientific, consulting fees from Boston Scientific, speakers fee from Abbott and Boston Scientific, and Support for attending meetings and travel from Abbott, and owns stock in Novo Nordisk. Dr. Kaiser reported receiving consulting fees from Unimedtec Switzerland and Swiss office of \u0026nbsp;federal health. Dr. Iglesias reported receiving grants from Biotronik, Concept Medical, and Terumo, consulting fees from Medtronic, Biotronik, Cordis, and ReCor Medical, speakers fees from Medtronic, Penumbra, Biotronik, Concept Medical, BRISTOL MYERS SQUIBB/PFIZER, Cordis, and Recor Medical, Support for attending meetings and travel from Biotronik, and participating Data Safety Monitoring Board of the CoSTAR trial (NCT04870424). Dr. Spirk reported receiving personal fees from Sanofi-Aventis (Switzerland) at the time of study conduct and Cook Medical outside the submitted work. Dr. Daemen reported receiving institutional grant/research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Pie Medical, and ReCor medical, and consultancy and speaker fees from Abbott Vascular, Abiomed, ACIST medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, ReCor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care and Medtronic. Dr Engstr\u0026oslash;m reported advisory board fees from Abbott and Novo Nordisk and speaker fees from Boston Scientific outside the submitted work. Dr. Lang has relationships with drug companies including AOP-Health, Actelion-Janssen, MSD, United Therapeutics, Pulnovo, Medtronic, INARI, Neutrolis and Sanofi. In addition to being investigator in trials involving these companies, relationships include consultancy service, research grants, and membership of scientific advisory boards. Dr. R\u0026auml;ber reported receiving grants from Sanofi, Regeneron, and Infraredx to Inselspital and speaker fees from Sanofi during the conduct of the study and grants from Abbott, Heartflow, Boston Scientific, and Biotronik to Inselspital and grants from Abbott, Amgen, AstraZeneca, Occlutech, Sanofi, Canon, and Medtronic for speaker and consultation fees outside the submitted work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe main PACMAN-AMI trial was funded by Sanofi, Regeneron, and Infraredx. Regeneron provided alirocumab and placebo free of charge. The current sub-study was conducted in an independent academic setting and funded by intramural grants of Bern University Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Ryota Kakizaki, Yasushi Ueki, Hiroki Shibutani, Flavio G. Biccir\u0026egrave;, Tatsuhiko Otsuka, Jonas D. H\u0026auml;ner, Jacob L\u0026oslash;nborg, Christoph Kaiser, Juan F. Iglesias, Anna S. Ondracek, David Spirk, George C. M. Siontis, Joost Daemen, Thomas Engstr\u0026oslash;m, Irene M. Lang, and Lorenz R\u0026auml;ber. Statistical analysis was done by Sylvain Losdat. The first draft of the manuscript was written by Ryota Kakizaki, Yasushi Ueki, and Konstantinos C. Koskinas. All authors commented on previous versions of the manuscript, and all read and approved the final version. Lorenz R\u0026auml;ber was responsible for supervision, conceptualization, and project administration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki, and the study was approved by the ethical committee at each site.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study, all patients provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants provided informed consent, acknowledging that their health-related and personal information (and samples) would be shared only in encrypted form for research purposes, including international collaboration, and that their names would not be published in any form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data set will be available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003ePiccolo R, Bonaa KH, Efthimiou O, Varenne O, Baldo A, et al. 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Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study. \u003cem\u003eCirculation\u003c/em\u003e. Sep 9 2008;118(11):1138-45. doi:10.1161/CIRCULATIONAHA.107.762047\u003c/li\u003e\n \u003cli\u003eKuroda M, Otake H, Shinke T, Takaya T, Nakagawa M, et al. The impact of in-stent neoatherosclerosis on long-term clinical outcomes: an observational study from the Kobe University Hospital optical coherence tomography registry. \u003cem\u003eEuroIntervention\u003c/em\u003e. Dec 10 2016;12(11):e1366-e1374. doi:10.4244/EIJY15M12_05\u003c/li\u003e\n \u003cli\u003eChen Z, Matsumura M, Mintz GS, Noguchi M, Fujimura T, et al. Prevalence and Impact of Neoatherosclerosis on Clinical Outcomes After Percutaneous Treatment of Second-Generation Drug-Eluting Stent Restenosis. \u003cem\u003eCirc Cardiovasc Interv\u003c/em\u003e. Sep 2022;15(9):e011693. doi:10.1161/CIRCINTERVENTIONS.121.011693\u003c/li\u003e\n \u003cli\u003eShimono H, Kajiya T, Takaoka J, Miyamura A, Inoue T, et al. Characteristics of recurrent in-stent restenosis after second- and third-generation drug-eluting stent implantation. \u003cem\u003eCoron Artery Dis\u003c/em\u003e. Jan 2021;32(1):36-41. doi:10.1097/MCA.0000000000000945\u003c/li\u003e\n \u003cli\u003eSchwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. \u003cem\u003eN Engl J Med\u003c/em\u003e. Nov 29 2018;379(22):2097-2107. doi:10.1056/NEJMoa1801174\u003c/li\u003e\n \u003cli\u003eRaber L, Ueki Y, Otsuka T, Losdat S, Haner JD, et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. \u003cem\u003eJAMA\u003c/em\u003e. May 10 2022;327(18):1771-1781. doi:10.1001/jama.2022.5218\u003c/li\u003e\n \u003cli\u003eZanchin C, Koskinas KC, Ueki Y, Losdat S, Haner JD, et al. Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-Rationale and design of the PACMAN-AMI trial. \u003cem\u003eAm Heart J\u003c/em\u003e. Aug 2021;238:33-44. doi:10.1016/j.ahj.2021.04.006\u003c/li\u003e\n \u003cli\u003eByrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. \u003cem\u003eEur Heart J\u003c/em\u003e. Oct 12 2023;44(38):3720-3826. doi:10.1093/eurheartj/ehad191\u003c/li\u003e\n \u003cli\u003eGuagliumi G, Shimamura K, Sirbu V, Garbo R, Boccuzzi G, et al. Temporal course of vascular healing and neoatherosclerosis after implantation of durable- or biodegradable-polymer drug-eluting stents. \u003cem\u003eEur Heart J\u003c/em\u003e. Jul 7 2018;39(26):2448-2456. doi:10.1093/eurheartj/ehy273\u003c/li\u003e\n \u003cli\u003eTearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. \u003cem\u003eJ Am Coll Cardiol\u003c/em\u003e. Mar 20 2012;59(12):1058-72. doi:10.1016/j.jacc.2011.09.079\u003c/li\u003e\n \u003cli\u003eHoshino M, Yonetsu T, Kanaji Y, Usui E, Yamaguchi M, et al. Impact of baseline plaque characteristic on the development of neoatherosclerosis in the very late phase after stenting. \u003cem\u003eJ Cardiol\u003c/em\u003e. Jul 2019;74(1):67-73. doi:10.1016/j.jjcc.2019.01.002\u003c/li\u003e\n \u003cli\u003eNagano Y, Otake H, Toba T, Kuroda K, Shinkura Y, et al. Impaired Cholesterol-Uptake Capacity of HDL Might Promote Target-Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation. \u003cem\u003eJ Am Heart Assoc\u003c/em\u003e. May 7 2019;8(9):e011975. doi:10.1161/JAHA.119.011975\u003c/li\u003e\n \u003cli\u003eNiccoli G, Dato I, Imaeva AE, Antonazzo Panico R, Roberto M, et al. Association between inflammatory biomarkers and in-stent restenosis tissue features: an Optical Coherence Tomography Study. \u003cem\u003eEur Heart J Cardiovasc Imaging\u003c/em\u003e. Aug 2014;15(8):917-25. doi:10.1093/ehjci/jeu035\u003c/li\u003e\n \u003cli\u003eCao YX, Li S, Liu HH, Li JJ. Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials. \u003cem\u003eBMJ Open\u003c/em\u003e. Oct 4 2018;8(9):e022348. doi:10.1136/bmjopen-2018-022348\u003c/li\u003e\n \u003cli\u003eTaniwaki M, Windecker S, Zaugg S, Stefanini GG, Baumgartner S, et al. The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study. \u003cem\u003eEur Heart J\u003c/em\u003e. Aug 21 2015;36(32):2167-76. doi:10.1093/eurheartj/ehv227\u003c/li\u003e\n \u003cli\u003eSakai R, Sekimoto T, Koba S, Mori H, Matsukawa N, et al. Impact of triglyceride-rich lipoproteins on early in-stent neoatherosclerosis formation in patients undergoing statin treatment. \u003cem\u003eJ Clin Lipidol\u003c/em\u003e. Mar-Apr 2023;17(2):281-290. doi:10.1016/j.jacl.2023.01.004\u003c/li\u003e\n \u003cli\u003eTaniwaki M, Haner JD, Kakizaki R, Ohno Y, Yahagi K, et al. Long-term effect of biodegradable vs durable polymer everolimus-eluting stents on neoatherosclerosis in ST-segment elevation myocardial infarction: the CONNECT trial. \u003cem\u003eEur Heart J\u003c/em\u003e. Sep 1 2024;doi:10.1093/eurheartj/ehae589\u003c/li\u003e\n \u003cli\u003eJang JY, Kim JS, Shin DH, Kim BK, Ko YG, et al. Favorable effect of optimal lipid-lowering therapy on neointimal tissue characteristics after drug-eluting stent implantation: qualitative optical coherence tomographic analysis. \u003cem\u003eAtherosclerosis\u003c/em\u003e. Oct 2015;242(2):553-9. doi:10.1016/j.atherosclerosis.2015.08.014\u003c/li\u003e\n \u003cli\u003eYonetsu T, Kim JS, Kato K, Kim SJ, Xing L, et al. Comparison of incidence and time course of neoatherosclerosis between bare metal stents and drug-eluting stents using optical coherence tomography. \u003cem\u003eAm J Cardiol\u003c/em\u003e. Oct 1 2012;110(7):933-9. doi:10.1016/j.amjcard.2012.05.027\u003c/li\u003e\n \u003cli\u003eSong L, Mintz GS, Yin D, Yamamoto MH, Chin CY, et al. Neoatherosclerosis assessed with optical coherence tomography in restenotic bare metal and first- and second-generation drug-eluting stents. \u003cem\u003eInt J Cardiovasc Imaging\u003c/em\u003e. Aug 2017;33(8):1115-1124. doi:10.1007/s10554-017-1106-2\u003c/li\u003e\n \u003cli\u003eLee SY, Hur SH, Lee SG, Kim SW, Shin DH, et al. Optical coherence tomographic observation of in-stent neoatherosclerosis in lesions with more than 50% neointimal area stenosis after second-generation drug-eluting stent implantation. \u003cem\u003eCirc Cardiovasc Interv\u003c/em\u003e. Feb 2015;8(2):e001878. doi:10.1161/CIRCINTERVENTIONS.114.001878\u003c/li\u003e\n \u003cli\u003eJinnouchi H, Otsuka F, Sato Y, Bhoite RR, Sakamoto A, et al. Healthy Strut Coverage After Coronary Stent Implantation: An Ex Vivo Human Autopsy Study. \u003cem\u003eCirc Cardiovasc Interv\u003c/em\u003e. May 2020;13(5):e008869. doi:10.1161/CIRCINTERVENTIONS.119.008869\u003cstrong\u003e\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-international-journal-of-cardiovascular-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caim","sideBox":"Learn more about [The International Journal of Cardiovascular Imaging](https://www.springer.com/journal/10554)","snPcode":"10554","submissionUrl":"https://submission.nature.com/new-submission/10554/3","title":"The International Journal of Cardiovascular Imaging","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"proprotein convertase subtilisin/kexin type 9 inhibitor, low-density lipoprotein cholesterol, neoatherosclerosis, neointimal hyperplasia","lastPublishedDoi":"10.21203/rs.3.rs-6592491/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6592491/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eHigher on-treatment levels of low-density lipoprotein cholesterol in statin-treated patients were reportedly associated with the occurrence of neoatherosclerosis after drug-eluting stent (DES) implantation.\u003cstrong\u003e \u003c/strong\u003eWe aimed to investigate the impact ofalirocumab added to high-intensity statin therapy on neoatherosclerosis formation among patients with acute myocardial infarction (AMI) treated with DES.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis was a pre-specified substudy of the PACMAN-AMI trial, a randomized, double-blind trial comparing alirocumab versus placebo added to high-intensity statin therapyin AMI patients. The present study included patients undergoing optical coherence tomography assessment of DES in the culprit lesion at one year. The frequency of neoatherosclerosis, neointimal thickness, and strut malapposition were compared between treatment groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAmong 191 patients (95 with alirocumab and 96 with placebo), neoatherosclerosis was observed in 13 patients (6.8%) at one year. There was no significant difference in the frequency of neoatherosclerosisbetween treatment groups (alirocumab 4.2% vs. placebo 9.4%, P=0.25). Among 11 patients with lipid-laden neointima, minimal fibrous cap thickness was greater in the alirocumab group than in the placebo group (217.5±122.5 vs. 87.8±49.1 μm, P=0.02). Neointimal thickness (136.2±71.1 vs. 151.4±101.4 μm, P=0.45) and the frequency of malapposed struts (0.94 vs. 0.53%, P=0.27) were comparable between treatment groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eAmong AMI patients treated with DES, there was no significant impact of alirocumab on the frequency of neoatherosclerosis and vessel healing at one year. The observed numerical difference and the finding of more stable neoatheroma in the alirocumab group need further investigation in larger studies with extended follow-up.\u003c/p\u003e","manuscriptTitle":"Impact of Alirocumab on Neoatherosclerosis Formation and Vessel Healing after Drug-eluting Stent Implantation in Patients with Acute Myocardial Infarction: a Substudy of the PACMAN-AMI Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 11:46:13","doi":"10.21203/rs.3.rs-6592491/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-08T14:33:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-01T12:55:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-28T15:39:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-21T09:54:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"195296114620786542282629209100740859389","date":"2025-05-17T13:28:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"205740597676102880164242548828379225222","date":"2025-05-17T11:51:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"292473234943681346145085129688469216196","date":"2025-05-07T10:01:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-07T08:58:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-06T02:07:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-06T02:06:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"The International Journal of Cardiovascular Imaging","date":"2025-05-05T08:11:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-international-journal-of-cardiovascular-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caim","sideBox":"Learn more about [The International Journal of Cardiovascular Imaging](https://www.springer.com/journal/10554)","snPcode":"10554","submissionUrl":"https://submission.nature.com/new-submission/10554/3","title":"The International Journal of Cardiovascular Imaging","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3c49fbc8-8ceb-4989-a287-de34500fdb4d","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-25T16:40:37+00:00","versionOfRecord":{"articleIdentity":"rs-6592491","link":"https://doi.org/10.1007/s10554-025-03472-0","journal":{"identity":"the-international-journal-of-cardiovascular-imaging","isVorOnly":false,"title":"The International Journal of Cardiovascular Imaging"},"publishedOn":"2025-08-18 16:29:42","publishedOnDateReadable":"August 18th, 2025"},"versionCreatedAt":"2025-05-13 11:46:13","video":"","vorDoi":"10.1007/s10554-025-03472-0","vorDoiUrl":"https://doi.org/10.1007/s10554-025-03472-0","workflowStages":[]},"version":"v1","identity":"rs-6592491","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6592491","identity":"rs-6592491","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}