Long-term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting in women, a meta-analysis

Long-term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting in women, a meta-analysis | 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 Long-term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting in women, a meta-analysis Daniel Pérez-Camargo, Paula Campelos-Fernández, Alejandro Travieso, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4637921/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Dec, 2024 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted 12 You are reading this latest preprint version Abstract Background Despite the advances in the last decades for treatment of ischemic heart disease, women continue to experience poorer prognosis than men and currently, there is a gap in knowledge regarding the optimal revascularization strategy in women. Objective Compare the long-term outcomes of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for the treatment of stable ischemic heart disease in women. Methods A systematic search was conducted including randomized clinical trials (RCTs) comparing PCI with drug-eluting stents with CABG. The primary outcome were the composite outcomes of death, stroke or myocardial infarction (MI) and death, stroke, MI or repeat revascularization. Secondary outcomes included the individual components of the primary outcomes. Pooled hazard ratios with 95% confidence intervals were calculated in a fixed- effects meta-analysis using the inverse of variance method. Risk of bias and sensitivity analyses were also conducted. Results Six multicenter, RCTs were included after eligibility assessment. Median follow-up was 6.25 years (IQR: 5- 2.5). A significant benefit for CABG over PCI was observed for the primary composite outcomes of death, stroke, MI (HR = 1.24; 95% CI 1.01–1.52; p = 0.037) and death, stroke, MI or repeat revascularization (HR = 1.60; 95% CI 1.25–2.03; p < 0.000). Conclusion In the present study-level metanalysis, CABG is associated with a lower risk of major adverse cardiovascular events than PCI at long term follow-up in women. Percutaneous Coronary Intervention drug eluting stent coronary artery bypass grafting female male sex Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1 Background Despite the advances in the last decades for treatment of ischemic heart disease, women continue to experience poorer prognosis than men. The cause is multifactorial, including biological factors, clinical delay in diagnosis and atypical presentation, among others[ 1 , 2 ]. Given that currently there is a gap in knowledge regarding the optimal revascularization strategy in women, we conducted a meta-analysis to compare the long-term outcomes of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for the treatment of stable ischemic heart disease in women. 2 Methods This meta-analysis was developed following the recommendations of the PRISMA statement[ 3 ] and the Cochrane Handbook for Systematic Reviews of Interventions[ 4 ]. 2.1 Ethics Given the nature of this study, patient consent was not required. 2.2 Systematic search A systematic search was conducted of the Cochrane Library, EMBASE, MEDLINE, Web of Science and conference abstracts in English language from database conception until June 2023. The search terms were: ("Percutaneous Coronary Intervention" AND "drug eluting stent") AND ("coronary artery bypass") AND ("female" OR "male" OR "men" OR "women" OR "sex") AND ("randomized controlled trial"[Publication Type]) AND (English [Language]). This study was registered in PROSPERO (International Prospective Register of Systematic Reviews) (CRD42022323279). 2.3 Eligibility criteria Eligible studies met the following PICOs criteria (participants, interventions, comparators, outcomes and study design): Population: Women with stable ischemic heart disease undergoing revascularization. Intervention: Myocardial revascularization. Comparison intervention: PCI with drug eluting stent (DES) or CABG for myocardial revascularization. Outcomes: At least 1 or more of the following outcomes or their composite at the longest follow-up available; Survival, myocardial infarction (MI), stroke and repeat revascularization. Outcomes had to be reported as crude events in each group or estimates (risk ratio, odds ratio, risk difference, mean difference) with 95% confidence intervals. Study design: Randomized clinical trials (RCT) comparing PCI with DES vs CABG Exclusion criteria: Studies with less than 5 years of follow-up. 2.4 Quality assessment Strength of evidence, consistency, precision, directness and publication bias was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system[ 5 ]. 2.5 Outcomes and data extraction The primary outcome was the composite outcome of death, stroke or myocardial infarction and death, stroke, myocardial infarction or repeat revascularization. Secondary outcomes included the individual components of the primary outcome. Authors, publication date, type of study, number of events, sample size, sex, age, type of devices employed for PCI and technical aspects of CABG were extracted. Only intention- to- treat analysis data was extracted. 2.6 Data analysis The estimates for each endpoint were combined using a fixed- effects meta-analysis by means of the inverse of variance method to determine the pooled hazard ratio (HR) of PCI compared to CABG. Heterogeneity between studies was evaluated using the I 2 statistic (An I 2 value 75% high heterogeneity) and the Q test (p < 0.10 for significant heterogeneity). Sensitivity analysis using the leave-one-out method and subgroup analyses examining the influence of left main disease (LM) dedicated RCTs on the primary endpoints were also performed. Forest plots were used to illustrate the pooled estimates. Risk of bias was assessed using the RoB 2 tool[ 6 ]. Funnel plots represented publication bias and heterogeneity for the primary endpoints. Two- sided P values of 0.05 were considered statistically significant. Statistical analyses were performed using Stata 17 (StataCorp, 2021. College Station, TX). 3 Results Six multicenter, RCTs were included after eligibility assessment (Fig. 1 )[ 7 – 13 ]. The overall quality of evidence using the GRADE system for the primary endpoints was moderate (Supplementary table 1 ), mainly due to some concerns regarding risk of bias and indirectness (Supplementary Figs. 1 and 2). Median follow-up was 6.25 years (IQR: 5- 2.5). The weighted median age of the patients at the time of inclusion was 65.1 years (IQR: 63.2–66) and the weighted median perioperative risk estimated with the EuroSCORE was 2.8% (IQR: 2.7–3.8). First generation DES were employed in the SYNTAX, PRECOMBAT and FREEDOM trials, and second-generation DES in the BEST, NOBLE and EXCEL trials. The median of arterial grafts employed was 1 (IQR 1–2). Characteristics of included studies are resumed in Table 1 . Different definitions of events were employed for each RCT, which are summarized in supplementary table 2 . The SYNTAX trial compared the composite of death, stroke, MI and repeat revascularization. 1800 patients were included, 903 in the PCI arm and 897 in the CABG arm; of those, 23.6% (n = 213) and 21.1% (n = 189) were women, respectively[ 7 ]. After completion of 5-year follow up, the study was continued as the SYNTAXES trial, which evaluated survival at 10-year follow-up[ 8 ]. The PRECOMBAT trial included patients with LM disease, and evaluated the composite of death, stroke, MI and repeat revascularization up to 10 years of follow-up. 300 patients were included in each arm, with 24% (n = 72) and 23% (n = 69) female patients for PCI and CABG, respectively[ 9 ]. The FREEDOM was designed to compare the composite of death, stroke and MI in patients with diabetes and multivessel coronary artery disease (CAD), and reported outcomes at 5 years of follow-up. 953 patients were included in the PCI arm and 947 in the CABG arm. 26.8% (n = 255) and 30.5% (n = 289) were women in each arm, respectively[ 10 ]. After study completion, the study continued as the FREEDOM Follow-On study, evaluating survival at 7.5 years of follow-up[ 14 ]. The BEST trial included 880 patients with multivessel CAD and compared the composite of death, MI and repeat revascularization up to 5-year follow-up. 30.6% (n = 134) were female patients in the PCI arm and 26.5 (n = 117) in the CABG arm[ 11 ]. The NOBLE and EXCEL trials included 1184 and 1905 patients with LM CAD, respectively, and reported outcomes at 5 years of follow up. The primary endpoint of NOBLE was the composite of death, stroke, MI and repeat revascularization while EXCEL evaluated a primary endpoint of death, stroke and MI. In the NOBLE trial, 20% (n = 116) and 24% (n = 140) were women in the PCI and CABG arms respectively. In the EXCEL trial 23.8% (n = 226) were women in the PCI arm and 22.5% (n = 215) in the CABG arm[ 12 , 13 ]. 3.1 Death, stroke, MI Five studies reported the composite endpoint of death, stroke or MI[ 7 , 9 – 11 , 13 ]. 25.1% (n = 1779) were female and 74.9% (n = 5306) male patients. In the pooled analysis, we observed a significant benefit favoring CABG over PCI (HR = 1.24; 95% CI 1.01–1.52; p = 0.037; I 2 = 0.0%) (Fig. 2 ). In the sensitivity analysis, the SYNTAX, FREEDOM and EXCEL studies had a significant influence in the composite outcome (Supplementary Fig. 3). In the subgroup analyses stratified by LM or multivessel RCT, no significant differences were found when evaluating only LM dedicated RCTs (Supplementary Fig. 4). 3.2 Death, stroke, MI, repeat revascularization The composite of death, stroke, MI or repeat revascularization was reported in 4 studies[ 7 , 9 , 11 , 12 ]. 23.5% (n = 1050) and 76.5% (n = 3414) were women and men, respectively. A significant benefit of CABG over PCI was observed in the pooled analysis (HR = 1.60; 95% CI 1.25–2.03; p < 0.000; I 2 = 25.7%) (Fig. 3 ). In the sensitivity analysis, the estimate from the SYNTAX trial significantly influenced the composite outcome (Supplementary Fig. 5). Results were consistent in the subgroup analysis for LM RCT’s (Supplementary Fig. 6). 3.3 Individual components of the primary outcomes Death was reported in four studies (n = 4277)[ 8 , 9 , 11 , 14 ], 26.3% (n = 1125) were women and 73.7% (n = 3152) men. In the pooled analysis, no significant difference between PCI and CABG was observed (HR = 1.02; 95% CI 0.82–1.25; p = 0.884; I 2 = 0.0%) (Fig. 4 A). Three studies reported the incidence of MI, repeat revascularization and stroke (n = 3280)[ 7 , 9 , 11 ]. 24.2% (n = 794) were women and 75,8% (n = 2486) were men. A significant benefit of CABG over PCI was observed in the pooled analysis for MI and repeat revascularization (MI HR = 2.15; 95% CI 1.06–4.35; p = 0.034; I 2 = 0.0%) (Repeat revascularization HR = 2.55; 95% CI 1.69–3.86; p < 0.000; I 2 = 0.0%), respectively (Fig. 4 B, 4 C). Regarding stroke, we observed no significant differences between treatments in the pooled analysis (HR = 0.55; 95% CI 0.25–1.21; p = 0.137; I 2 = 0.0%) (Fig. 4 D). 4 Discussion We have conducted a study-level metanalysis including all contemporary RCTs with at least 5 years of follow up comparing PCI versus CABG in women (Central figure). Our main findings are the following: There is a significant benefit of CABG over PCI in for the composite outcome of death, MI, stroke and repeat revascularization. 2) Women were largely underrepresented in contemporary RCTs, with less than 30% of included patients. The benefit of CABG over PCI in the composite endpoint was mainly driven by a reduction in MI and repeat revascularization events in CABG patients, without significant differences in death or stroke. Even though the main cause of ischemic heart disease in both sexes is atherosclerosis, women present different patterns of disease, usually less extensive with smaller vessel lumen, tortuous anatomy and high risk for coronary artery dissection, making revascularization procedures more technically demanding. In this setting, CABG might offer several advantages to overcome these challenges: restores distal flow irrespective of lesion characteristics, protects from proximal plaque progression in the treated vessel, and complete revascularization is often achieved at the time of the index procedure[ 15 – 18 ]. In addition, conduit patency in CABG grafts ranges from 50% at 10 years for saphenous vein grafts to 98% at 20 years for left internal thoracic artery grafts, with evidence of reduction in major adverse cardiovascular events when multiple arterial grafting is employed[ 19 – 22 ]. On the other hand, DES restenosis at 8 month follow up may be present in 12.2–14.6% of patients in large registries, with an incidence of repeat revascularization and target lesion failure within 5 years of 12.2 to 13.3% and 7.7–9.5%, respectively[ 23 , 24 ]. The influence of guideline directed medical therapy in long term outcomes is out of the scope of this study given the lack of patient-level data. Nonetheless, two RCTs reported long term medication therapy according to sex, showing that women overall had worse adherence to medical therapy, and specifically, women who underwent CABG had significantly lower adherence to antiplatelet and statin therapy[ 8 , 9 ]. Our results are in concordance with two previous metanalyses which reported similar findings in women and men. Nevertheless, the patient-level metanalysis by Stomi, Y et al included only 3 RCT’s with a median follow up of 4.9 years and the study-level metanalysis by Gul, B et al included studies with less than 5 years of follow-up[ 25 , 26 ]. To our knowledge, our study is the first to include all contemporary RCT’s with long-term results. Current guidelines in myocardial revascularization do not have sex-specific recommendations while the supporting evidence is not equal among women and men[ 27 , 28 ]. The development, progression, clinical manifestations and response to treatment of ischemic heart disease is different between sex and it should be acknowledged that current recommendations may be biased regarding women. 5 Limitations Several limitations should be accounted when interpreting the data form the present study: First, even though we only included RCTs with DES, stent technology, conduit selection, medical therapy, interventional and surgical techniques have improved over the last decade and may not reflect current practice. Second, the evaluation of CAD has also evolved, incorporating intracoronary physiology and imaging as tools to determine the functional significant of coronary stenoses. The use of intracoronary imaging to guide PCI has demonstrated better outcomes compared to angiography guidance alone. In the aforementioned trials, the overall use of intracoronary imaging was low, even though the impact of imaging-guided PCI is more pronounced in patients with complex and multivessel CAD[ 29 , 30 ]. Third, patient-level data was not available, thus further subgroup analyses and adjustment could not be performed. Finally, different definitions for clinical endpoints were used in each RCT, which may be a source of bias. Some of these limitations may be overcome by the upcoming ROMA: Women trial (NCT04124120). However, given the continuous evolution of both surgical and percutaneous revascularization techniques, furthers studies integrating contemporary practices are warranted. 6 Conclusion In the present study-level metanalysis, CABG is associated with a lower risk of major adverse cardiovascular events than PCI at long term follow-up in women. Abbreviations PCI Percutaneous coronary intervention CABG Coronary artery bypass grafting DES Drug eluting stent MI Myocardial infarction RCT Randomized clinical trial HR Hazard ratio LM Left main coronary artery CAD Coronary artery disease OPCABG Off-pump coronary artery bypass grafting Declarations Ethics Given the nature of this study, patient consent was not required. Data availability statement The data underlying this article are available in the article and in its online supplementary material. Disclosure statement The authors declare that there are no material or financial interests related to the research described in this article. Funding statement The authors received no financial support for the research, authorship and/or publication of this article. 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Table 1 Table 1: Characteristics of included studies Values are mean (± SD), n (%) or median (IQR) N/A: Not available; RCT: Randomized controlled trial; PCI: Percutaneous coronary intervention; CABG: Coronary artery bypass graft; CAD: Coronary artery disease; OPCABG: Off-pump CABG; LM: Left main. PCI CABG Study, year Type of study Primary endpoint Type of CAD Follow-up n Age (SD) Female (%) EuroScore (SD) Type of stent Complete revascularization (%) n Age Female EuroScore No. arterial grafts OPCABG Complete revascularization (%) SYNTAX, 2009 RCT, noninferiority Death, stroke, MI, repeat revascularization LM, multivessel 10 years 903 65.2 (9.7) 213 (23.6) 3.8 (2,5) Paclitaxel (1 st Gen) 512 (56.7) 897 65 (9.8) 189 (21.1) 3.8 (2.7) 1 (1-2) 128 (14,2) 566 (63.2) PRECOMBAT, 2011 RCT, noninferiority Death, stroke, MI, repeat revascularization LM 10 years 300 61.8 (10) 72 (24) 2.6 (1.8) Sirolimus (1 st Gen) 205 (68.3) 300 62.7 (9.5) 69 (23) 2.8 (1.9) 2 (1-3) 155 (63.8) 211 (70.3) FREEDOM, 2012 RCT, superiority Death, stroke, MI Multivessel 7.5 years 953 63.2 (8.9) 255 (26.8) 2.7 (2.4) Sirolimus/ Paclitaxel (1 st Gen) N/A 947 63.1 (9.2) 289 (30.5) 2.8 (2.5) N/A 165 (18.5) N/A BEST, 2015 RCT, noninferiority Death, MI, repeat revascularization Multivessel 5 years 438 64 (9.3) 134 (30.6) 2.9 (2) Everolimus (2 nd Gen) 236 (50.9) 442 64.9 (9.4) 117 (26.5) 3 (2.1) 2 (1-2) 258 (64.3) 274 (71.5) NOBLE, 2016 RCT, noninferiority Death, stroke, MI, repeat revascularization LM 5 years 592 66.2 (9.9 116 (20) 2 (2.1) Biolimus (2 nd Gen) 543 (94.1) 592 66.2 (9.4) 140 (24) 2 (1.9) 1 (1-2) 88 (15.6) N/A EXCEL, 2016 RCT, noninferiority Death, stroke, MI LM 5 years 948 66 (9.6) 226 (23.8) N/A Everolimus (2 nd Gen) N/A 957 65.9 (9.5) 215 (22.5) N/A 1 (1-2) 271 (29.4) N/A Additional Declarations No competing interests reported. Supplementary Files PRISMAchecklist.pdf SupplementaryMaterial1.5.pdf Supplementarytable1.docx Supplementarytable2.docx Cite Share Download PDF Status: Published Journal Publication published 20 Dec, 2024 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted Editorial decision: Revision requested 08 Sep, 2024 Reviews received at journal 27 Aug, 2024 Reviews received at journal 11 Aug, 2024 Reviews received at journal 10 Aug, 2024 Reviewers agreed at journal 05 Aug, 2024 Reviewers agreed at journal 04 Aug, 2024 Reviewers agreed at journal 04 Aug, 2024 Reviewers agreed at journal 02 Aug, 2024 Reviewers invited by journal 02 Aug, 2024 Editor assigned by journal 01 Jul, 2024 Submission checks completed at journal 01 Jul, 2024 First submitted to journal 25 Jun, 2024 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. 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Maroto-Castellanos","email":"","orcid":"","institution":"Hospital Universitario Clínico San Carlos","correspondingAuthor":false,"prefix":"","firstName":"Luis","middleName":"C.","lastName":"Maroto-Castellanos","suffix":""}],"badges":[],"createdAt":"2024-06-25 16:42:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4637921/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4637921/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13019-024-03167-y","type":"published","date":"2024-12-20T15:58:04+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60943738,"identity":"15f05d7b-ce85-44b5-9c07-e57e0f7caf99","added_by":"auto","created_at":"2024-07-23 22:03:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":176381,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram of the meta-analysis.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/ddd9229fd517ef94a62c81c1.png"},{"id":60944549,"identity":"aad3e824-e49f-477d-a39e-3a5fb634dcbb","added_by":"auto","created_at":"2024-07-23 22:11:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":240319,"visible":true,"origin":"","legend":"\u003cp\u003eInverse of variance fixed- effects Hazard Ratio and 95% CI for death, stroke, MI.\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval; MI: Myocardial infarction\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/16d67357aba0318ffdcc7fc8.png"},{"id":60944550,"identity":"500b73a4-0072-4ccb-a77f-486cad97482d","added_by":"auto","created_at":"2024-07-23 22:11:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":232631,"visible":true,"origin":"","legend":"\u003cp\u003eInverse of variance fixed- effects Hazard Ratio and 95% CI for death, stroke, MI, repeat revascularization.\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval; MI: Myocardial infarction.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/01bc8dbb56122358dfe40179.png"},{"id":60944551,"identity":"7df0c53d-8561-49e3-a555-521433850713","added_by":"auto","created_at":"2024-07-23 22:11:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1392494,"visible":true,"origin":"","legend":"\u003cp\u003eInverse of variance fixed- effects Hazard Ratio and 95% CI for A) Death; B) MI; C) Repeat revascularization; D) Stroke.\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval; MI: Myocardial infarction.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/54779d1a38fbd35ba42b159f.png"},{"id":60944552,"identity":"6c171e4e-5bbf-4d7a-829e-c0e392385c3f","added_by":"auto","created_at":"2024-07-23 22:11:57","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":499765,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCentral figure. \u003c/strong\u003eStudy-level metanalysis including all contemporary RCTs with at least 5 years of follow up comparing PCI versus CABG in women.\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval; MI: Myocardial infarction.\u003c/p\u003e","description":"","filename":"Centralfigure1.2.png","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/c61c6390adf3b3af52f6c1b2.png"},{"id":72201920,"identity":"e35fbdca-4a5a-447f-8d2e-dae94b88f2ff","added_by":"auto","created_at":"2024-12-23 16:12:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2748728,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/66610154-b27d-44bb-964d-5dc28294cf3c.pdf"},{"id":60943736,"identity":"7b6a3ab1-eda1-41b1-be2b-0a8f64005099","added_by":"auto","created_at":"2024-07-23 22:03:57","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":85383,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMAchecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/af3ab7ca91f1298e6d1689da.pdf"},{"id":60943761,"identity":"c19c3b96-afcd-4c74-8ccb-596c4344ded3","added_by":"auto","created_at":"2024-07-23 22:03:57","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1521656,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial1.5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/8cb8aef4fe5f04fe8f5b6742.pdf"},{"id":60943741,"identity":"492a3b90-a5f2-4401-aa61-282333a75824","added_by":"auto","created_at":"2024-07-23 22:03:57","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":13039,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/a785a0ccdb8de9f172726c46.docx"},{"id":60943740,"identity":"1fa542df-344e-4f53-95ff-32ec563954ac","added_by":"auto","created_at":"2024-07-23 22:03:57","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":16516,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4637921/v1/09d26ceaf1bb8d11d9601495.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting in women, a meta-analysis","fulltext":[{"header":"1 Background","content":"\u003cp\u003eDespite the advances in the last decades for treatment of ischemic heart disease, women continue to experience poorer prognosis than men. The cause is multifactorial, including biological factors, clinical delay in diagnosis and atypical presentation, among others[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Given that currently there is a gap in knowledge regarding the optimal revascularization strategy in women, we conducted a meta-analysis to compare the long-term outcomes of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for the treatment of stable ischemic heart disease in women.\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cp\u003eThis meta-analysis was developed following the recommendations of the PRISMA statement[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and the Cochrane Handbook for Systematic Reviews of Interventions[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Ethics\u003c/h2\u003e \u003cp\u003eGiven the nature of this study, patient consent was not required.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Systematic search\u003c/h2\u003e \u003cp\u003eA systematic search was conducted of the Cochrane Library, EMBASE, MEDLINE, Web of Science and conference abstracts in English language from database conception until June 2023. The search terms were:\u003c/p\u003e \u003cp\u003e(\"Percutaneous Coronary Intervention\" AND \"drug eluting stent\") AND (\"coronary artery bypass\") AND (\"female\" OR \"male\" OR \"men\" OR \"women\" OR \"sex\") AND (\"randomized controlled trial\"[Publication Type]) AND (English [Language]).\u003c/p\u003e \u003cp\u003e This study was registered in PROSPERO (International Prospective Register of Systematic Reviews) (CRD42022323279).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Eligibility criteria\u003c/h2\u003e \u003cp\u003eEligible studies met the following PICOs criteria (participants, interventions, comparators, outcomes and study design):\u003c/p\u003e \u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePopulation: Women with stable ischemic heart disease undergoing revascularization.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eIntervention: Myocardial revascularization.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eComparison intervention: PCI with drug eluting stent (DES) or CABG for myocardial revascularization.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eOutcomes: At least 1 or more of the following outcomes or their composite at the longest follow-up available; Survival, myocardial infarction (MI), stroke and repeat revascularization. Outcomes had to be reported as crude events in each group or estimates (risk ratio, odds ratio, risk difference, mean difference) with 95% confidence intervals.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eStudy design: Randomized clinical trials (RCT) comparing PCI with DES vs CABG\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e Exclusion criteria: Studies with less than 5 years of follow-up.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Quality assessment\u003c/h2\u003e \u003cp\u003eStrength of evidence, consistency, precision, directness and publication bias was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Outcomes and data extraction\u003c/h2\u003e \u003cp\u003eThe primary outcome was the composite outcome of death, stroke or myocardial infarction and death, stroke, myocardial infarction or repeat revascularization. Secondary outcomes included the individual components of the primary outcome. Authors, publication date, type of study, number of events, sample size, sex, age, type of devices employed for PCI and technical aspects of CABG were extracted. Only intention- to- treat analysis data was extracted.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Data analysis\u003c/h2\u003e \u003cp\u003eThe estimates for each endpoint were combined using a fixed- effects meta-analysis by means of the inverse of variance method to determine the pooled hazard ratio (HR) of PCI compared to CABG. Heterogeneity between studies was evaluated using the I\u003csup\u003e2\u003c/sup\u003e statistic (An I\u003csup\u003e2\u003c/sup\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;25% was considered low; I\u003csup\u003e2\u003c/sup\u003e between 25%- 75% moderate and I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026gt;\u0026thinsp;75% high heterogeneity) and the Q test (p\u0026thinsp;\u0026lt;\u0026thinsp;0.10 for significant heterogeneity). Sensitivity analysis using the leave-one-out method and subgroup analyses examining the influence of left main disease (LM) dedicated RCTs on the primary endpoints were also performed. Forest plots were used to illustrate the pooled estimates. Risk of bias was assessed using the RoB 2 tool[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Funnel plots represented publication bias and heterogeneity for the primary endpoints. Two- sided P values of 0.05 were considered statistically significant. Statistical analyses were performed using Stata 17 (StataCorp, 2021. College Station, TX).\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cp\u003eSix multicenter, RCTs were included after eligibility assessment (Fig. \u003cspan\u003e1\u003c/span\u003e)[\u003cspan\u003e7\u003c/span\u003e\u0026ndash;\u003cspan\u003e13\u003c/span\u003e]. The overall quality of evidence using the GRADE system for the primary endpoints was moderate (Supplementary table \u003cspan\u003e1\u003c/span\u003e), mainly due to some concerns regarding risk of bias and indirectness (Supplementary Figs. 1 and 2). Median follow-up was 6.25 years (IQR: 5- 2.5). The weighted median age of the patients at the time of inclusion was 65.1 years (IQR: 63.2\u0026ndash;66) and the weighted median perioperative risk estimated with the EuroSCORE was 2.8% (IQR: 2.7\u0026ndash;3.8). First generation DES were employed in the SYNTAX, PRECOMBAT and FREEDOM trials, and second-generation DES in the BEST, NOBLE and EXCEL trials. The median of arterial grafts employed was 1 (IQR 1\u0026ndash;2). Characteristics of included studies are resumed in Table \u003cspan\u003e1\u003c/span\u003e. Different definitions of events were employed for each RCT, which are summarized in supplementary table \u003cspan\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eThe SYNTAX trial compared the composite of death, stroke, MI and repeat revascularization. 1800 patients were included, 903 in the PCI arm and 897 in the CABG arm; of those, 23.6% (n\u0026thinsp;=\u0026thinsp;213) and 21.1% (n\u0026thinsp;=\u0026thinsp;189) were women, respectively[\u003cspan\u003e7\u003c/span\u003e]. After completion of 5-year follow up, the study was continued as the SYNTAXES trial, which evaluated survival at 10-year follow-up[\u003cspan\u003e8\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe PRECOMBAT trial included patients with LM disease, and evaluated the composite of death, stroke, MI and repeat revascularization up to 10 years of follow-up. 300 patients were included in each arm, with 24% (n\u0026thinsp;=\u0026thinsp;72) and 23% (n\u0026thinsp;=\u0026thinsp;69) female patients for PCI and CABG, respectively[\u003cspan\u003e9\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe FREEDOM was designed to compare the composite of death, stroke and MI in patients with diabetes and multivessel coronary artery disease (CAD), and reported outcomes at 5 years of follow-up. 953 patients were included in the PCI arm and 947 in the CABG arm. 26.8% (n\u0026thinsp;=\u0026thinsp;255) and 30.5% (n\u0026thinsp;=\u0026thinsp;289) were women in each arm, respectively[\u003cspan\u003e10\u003c/span\u003e]. After study completion, the study continued as the FREEDOM Follow-On study, evaluating survival at 7.5 years of follow-up[\u003cspan\u003e14\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe BEST trial included 880 patients with multivessel CAD and compared the composite of death, MI and repeat revascularization up to 5-year follow-up. 30.6% (n\u0026thinsp;=\u0026thinsp;134) were female patients in the PCI arm and 26.5 (n\u0026thinsp;=\u0026thinsp;117) in the CABG arm[\u003cspan\u003e11\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe NOBLE and EXCEL trials included 1184 and 1905 patients with LM CAD, respectively, and reported outcomes at 5 years of follow up. The primary endpoint of NOBLE was the composite of death, stroke, MI and repeat revascularization while EXCEL evaluated a primary endpoint of death, stroke and MI. In the NOBLE trial, 20% (n\u0026thinsp;=\u0026thinsp;116) and 24% (n\u0026thinsp;=\u0026thinsp;140) were women in the PCI and CABG arms respectively. In the EXCEL trial 23.8% (n\u0026thinsp;=\u0026thinsp;226) were women in the PCI arm and 22.5% (n\u0026thinsp;=\u0026thinsp;215) in the CABG arm[\u003cspan\u003e12\u003c/span\u003e, \u003cspan\u003e13\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003e3.1 Death, stroke, MI\u003c/h2\u003e\n \u003cp\u003eFive studies reported the composite endpoint of death, stroke or MI[\u003cspan\u003e7\u003c/span\u003e, \u003cspan\u003e9\u003c/span\u003e\u0026ndash;\u003cspan\u003e11\u003c/span\u003e, \u003cspan\u003e13\u003c/span\u003e]. 25.1% (n\u0026thinsp;=\u0026thinsp;1779) were female and 74.9% (n\u0026thinsp;=\u0026thinsp;5306) male patients. In the pooled analysis, we observed a significant benefit favoring CABG over PCI (HR\u0026thinsp;=\u0026thinsp;1.24; 95% CI 1.01\u0026ndash;1.52; p\u0026thinsp;=\u0026thinsp;0.037; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.0%) (Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e). In the sensitivity analysis, the SYNTAX, FREEDOM and EXCEL studies had a significant influence in the composite outcome (Supplementary Fig.\u0026nbsp;3). In the subgroup analyses stratified by LM or multivessel RCT, no significant differences were found when evaluating only LM dedicated RCTs (Supplementary Fig.\u0026nbsp;4).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003e3.2 Death, stroke, MI, repeat revascularization\u003c/h2\u003e\n \u003cp\u003eThe composite of death, stroke, MI or repeat revascularization was reported in 4 studies[\u003cspan\u003e7\u003c/span\u003e, \u003cspan\u003e9\u003c/span\u003e, \u003cspan\u003e11\u003c/span\u003e, \u003cspan\u003e12\u003c/span\u003e]. 23.5% (n\u0026thinsp;=\u0026thinsp;1050) and 76.5% (n\u0026thinsp;=\u0026thinsp;3414) were women and men, respectively. A significant benefit of CABG over PCI was observed in the pooled analysis (HR\u0026thinsp;=\u0026thinsp;1.60; 95% CI 1.25\u0026ndash;2.03; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;25.7%) (Fig.\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e). In the sensitivity analysis, the estimate from the SYNTAX trial significantly influenced the composite outcome (Supplementary Fig.\u0026nbsp;5). Results were consistent in the subgroup analysis for LM RCT\u0026rsquo;s (Supplementary Fig.\u0026nbsp;6).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003e3.3 Individual components of the primary outcomes\u003c/h2\u003e\n \u003cp\u003eDeath was reported in four studies (n\u0026thinsp;=\u0026thinsp;4277)[\u003cspan\u003e8\u003c/span\u003e, \u003cspan\u003e9\u003c/span\u003e, \u003cspan\u003e11\u003c/span\u003e, \u003cspan\u003e14\u003c/span\u003e], 26.3% (n\u0026thinsp;=\u0026thinsp;1125) were women and 73.7% (n\u0026thinsp;=\u0026thinsp;3152) men. In the pooled analysis, no significant difference between PCI and CABG was observed (HR\u0026thinsp;=\u0026thinsp;1.02; 95% CI 0.82\u0026ndash;1.25; p\u0026thinsp;=\u0026thinsp;0.884; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.0%) (Fig.\u0026nbsp;\u003cspan\u003e4\u003c/span\u003eA). Three studies reported the incidence of MI, repeat revascularization and stroke (n\u0026thinsp;=\u0026thinsp;3280)[\u003cspan\u003e7\u003c/span\u003e, \u003cspan\u003e9\u003c/span\u003e, \u003cspan\u003e11\u003c/span\u003e]. 24.2% (n\u0026thinsp;=\u0026thinsp;794) were women and 75,8% (n\u0026thinsp;=\u0026thinsp;2486) were men. A significant benefit of CABG over PCI was observed in the pooled analysis for MI and repeat revascularization (MI HR\u0026thinsp;=\u0026thinsp;2.15; 95% CI 1.06\u0026ndash;4.35; p\u0026thinsp;=\u0026thinsp;0.034; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.0%) (Repeat revascularization HR\u0026thinsp;=\u0026thinsp;2.55; 95% CI 1.69\u0026ndash;3.86; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.0%), respectively (Fig.\u0026nbsp;\u003cspan\u003e4\u003c/span\u003eB, \u003cspan\u003e4\u003c/span\u003eC). Regarding stroke, we observed no significant differences between treatments in the pooled analysis (HR\u0026thinsp;=\u0026thinsp;0.55; 95% CI 0.25\u0026ndash;1.21; p\u0026thinsp;=\u0026thinsp;0.137; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.0%) (Fig.\u0026nbsp;\u003cspan\u003e4\u003c/span\u003eD).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eWe have conducted a study-level metanalysis including all contemporary RCTs with at least 5 years of follow up comparing PCI versus CABG in women (Central figure). Our main findings are the following:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThere is a significant benefit of CABG over PCI in for the composite outcome of death, MI, stroke and repeat revascularization.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e\n\u003ch3\u003e2) Women were largely underrepresented in contemporary RCTs, with less than 30% of included patients.\u003c/h3\u003e\n\u003cp\u003eThe benefit of CABG over PCI in the composite endpoint was mainly driven by a reduction in MI and repeat revascularization events in CABG patients, without significant differences in death or stroke. Even though the main cause of ischemic heart disease in both sexes is atherosclerosis, women present different patterns of disease, usually less extensive with smaller vessel lumen, tortuous anatomy and high risk for coronary artery dissection, making revascularization procedures more technically demanding. In this setting, CABG might offer several advantages to overcome these challenges: restores distal flow irrespective of lesion characteristics, protects from proximal plaque progression in the treated vessel, and complete revascularization is often achieved at the time of the index procedure[\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In addition, conduit patency in CABG grafts ranges from 50% at 10 years for saphenous vein grafts to 98% at 20 years for left internal thoracic artery grafts, with evidence of reduction in major adverse cardiovascular events when multiple arterial grafting is employed[\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. On the other hand, DES restenosis at 8 month follow up may be present in 12.2\u0026ndash;14.6% of patients in large registries, with an incidence of repeat revascularization and target lesion failure within 5 years of 12.2 to 13.3% and 7.7\u0026ndash;9.5%, respectively[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e The influence of guideline directed medical therapy in long term outcomes is out of the scope of this study given the lack of patient-level data. Nonetheless, two RCTs reported long term medication therapy according to sex, showing that women overall had worse adherence to medical therapy, and specifically, women who underwent CABG had significantly lower adherence to antiplatelet and statin therapy[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur results are in concordance with two previous metanalyses which reported similar findings in women and men. Nevertheless, the patient-level metanalysis by Stomi, Y et al included only 3 RCT\u0026rsquo;s with a median follow up of 4.9 years and the study-level metanalysis by Gul, B et al included studies with less than 5 years of follow-up[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. To our knowledge, our study is the first to include all contemporary RCT\u0026rsquo;s with long-term results.\u003c/p\u003e \u003cp\u003eCurrent guidelines in myocardial revascularization do not have sex-specific recommendations while the supporting evidence is not equal among women and men[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The development, progression, clinical manifestations and response to treatment of ischemic heart disease is different between sex and it should be acknowledged that current recommendations may be biased regarding women.\u003c/p\u003e"},{"header":"5 Limitations","content":"\u003cp\u003eSeveral limitations should be accounted when interpreting the data form the present study:\u003c/p\u003e \u003cp\u003eFirst, even though we only included RCTs with DES, stent technology, conduit selection, medical therapy, interventional and surgical techniques have improved over the last decade and may not reflect current practice. Second, the evaluation of CAD has also evolved, incorporating intracoronary physiology and imaging as tools to determine the functional significant of coronary stenoses. The use of intracoronary imaging to guide PCI has demonstrated better outcomes compared to angiography guidance alone. In the aforementioned trials, the overall use of intracoronary imaging was low, even though the impact of imaging-guided PCI is more pronounced in patients with complex and multivessel CAD[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Third, patient-level data was not available, thus further subgroup analyses and adjustment could not be performed. Finally, different definitions for clinical endpoints were used in each RCT, which may be a source of bias. Some of these limitations may be overcome by the upcoming ROMA: Women trial (NCT04124120). However, given the continuous evolution of both surgical and percutaneous revascularization techniques, furthers studies integrating contemporary practices are warranted.\u003c/p\u003e"},{"header":"6 Conclusion","content":"\u003cp\u003eIn the present study-level metanalysis, CABG is associated with a lower risk of major adverse cardiovascular events than PCI at long term follow-up in women.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003ePCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.98233215547704%\" valign=\"top\"\u003e\n \u003cp\u003ePercutaneous coronary intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003eCABG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.98233215547704%\" valign=\"top\"\u003e\n \u003cp\u003eCoronary artery bypass grafting\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003eDES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.98233215547704%\" valign=\"top\"\u003e\n \u003cp\u003eDrug eluting stent\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003eMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.98233215547704%\" valign=\"top\"\u003e\n \u003cp\u003eMyocardial infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.98233215547704%\" valign=\"top\"\u003e\n \u003cp\u003eRandomized clinical trial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.98233215547704%\" valign=\"top\"\u003e\n \u003cp\u003eHazard ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003eLM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.98233215547704%\" valign=\"top\"\u003e\n \u003cp\u003eLeft main coronary artery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003eCAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.98233215547704%\" valign=\"top\"\u003e\n \u003cp\u003eCoronary artery disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003eOPCABG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"84.98233215547704%\" valign=\"top\"\u003e\n \u003cp\u003eOff-pump coronary artery bypass grafting\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the nature of this study, patient consent was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this article are available in the article and in its online supplementary material.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no material or financial interests related to the research described in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for the research, authorship and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception: DPC, PC, AT\u003c/p\u003e\n\u003cp\u003eData acquisition: DPC, AT, LM\u003c/p\u003e\n\u003cp\u003eData analysis and interpretation: DPC, MCA, COB, JCC\u003c/p\u003e\n\u003cp\u003eManuscript revision AAA, FRL, LMC, MCA, COB\u003c/p\u003e\n\u003cp\u003eManuscript approval: All authors\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. 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N Engl J Med. 2018;378:2069\u0026ndash;77.\u003c/li\u003e\n\u003cli\u003eSamadashvili Z, Sundt TM, Wechsler A, Chikwe J, Adams DH, Smith CR, et al. Multiple Versus Single Arterial Coronary Bypass Graft Surgery for Multivessel Disease. J Am Coll Cardiol. 2019;74:1275\u0026ndash;85.\u003c/li\u003e\n\u003cli\u003eGaudino M, Audisio K, Di Franco A, Alexander JH, Kurlansky P, Boening A, et al. Radial artery versus saphenous vein versus right internal thoracic artery for coronary artery bypass grafting. Eur J Cardiothorac Surg. 2022;62.\u003c/li\u003e\n\u003cli\u003eMadhavan M V., Kirtane AJ, Redfors B, G\u0026eacute;n\u0026eacute;reux P, Ben-Yehuda O, Palmerini T, et al. Stent-Related Adverse Events \u0026gt;1 Year After Percutaneous Coronary Intervention. J Am Coll Cardiol. 2020;75:590\u0026ndash;604.\u003c/li\u003e\n\u003cli\u003eCassese S, Byrne RA, Tada T, Pinieck S, Joner M, Ibrahim T, et al. 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Eur Heart J. 2019;40:87\u0026ndash;165.\u003c/li\u003e\n\u003cli\u003eLawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79:e21\u0026ndash;129.\u003c/li\u003e\n\u003cli\u003eLee JM, Choi KH, Song Y Bin, Lee J-Y, Lee S-J, Lee SY, et al. Intravascular Imaging-Guided or Angiography-Guided Complex PCI. N Engl J Med. 2023;388:1668\u0026ndash;79.\u003c/li\u003e\n\u003cli\u003eEscaned J, Berry C, De Bruyne B, Shabbir A, Collet C, Lee JM, et al. Applied coronary physiology for planning and guidance of percutaneous coronary interventions. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology. EuroIntervention. 2023;19:464\u0026ndash;81.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1: Characteristics of included studies\u003c/p\u003e\n\u003cp\u003eValues are mean (\u0026plusmn;\u0026nbsp;SD), n (%) or median (IQR)\u003c/p\u003e\n\u003cp\u003eN/A: Not available; RCT: Randomized controlled trial; PCI: Percutaneous coronary intervention; CABG: Coronary artery bypass graft; CAD: Coronary artery disease; OPCABG: Off-pump CABG; LM: Left main.\u0026nbsp;\u003c/p\u003e\n\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1038\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.26371511068335%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.41385948026949%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003ePCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.32242540904716%\" colspan=\"7\" valign=\"top\"\u003e\n \u003cp\u003eCABG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003eStudy, year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.142857142857143%\" valign=\"top\"\u003e\n \u003cp\u003eType of study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003ePrimary endpoint\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.177606177606178%\" valign=\"top\"\u003e\n \u003cp\u003eType of CAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.633204633204633%\" valign=\"top\"\u003e\n \u003cp\u003eFollow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3783783783783785%\" valign=\"top\"\u003e\n \u003cp\u003eAge (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003eEuroScore\u003c/p\u003e\n \u003cp\u003e(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.405405405405405%\" valign=\"top\"\u003e\n \u003cp\u003eType of stent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eComplete revascularization\u003c/p\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.474903474903475%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003eEuroScore\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.343629343629344%\" valign=\"top\"\u003e\n \u003cp\u003eNo. arterial grafts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.888030888030888%\" valign=\"top\"\u003e\n \u003cp\u003eOPCABG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eComplete revascularization (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003eSYNTAX, 2009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.142857142857143%\" valign=\"top\"\u003e\n \u003cp\u003eRCT, noninferiority\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eDeath, stroke, MI, repeat revascularization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.177606177606178%\" valign=\"top\"\u003e\n \u003cp\u003eLM, multivessel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.633204633204633%\" valign=\"top\"\u003e\n \u003cp\u003e10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e903\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3783783783783785%\" valign=\"top\"\u003e\n \u003cp\u003e65.2 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e213 (23.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e3.8\u003c/p\u003e\n \u003cp\u003e(2,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.405405405405405%\" valign=\"top\"\u003e\n \u003cp\u003ePaclitaxel (1\u003csup\u003est\u003c/sup\u003e Gen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003e512 (56.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e897\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.474903474903475%\" valign=\"top\"\u003e\n \u003cp\u003e65 (9.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e189 (21.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e3.8 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.343629343629344%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.888030888030888%\" valign=\"top\"\u003e\n \u003cp\u003e128 (14,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003e566 (63.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003ePRECOMBAT, 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.142857142857143%\" valign=\"top\"\u003e\n \u003cp\u003eRCT, noninferiority\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eDeath, stroke, MI, repeat revascularization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.177606177606178%\" valign=\"top\"\u003e\n \u003cp\u003eLM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.633204633204633%\" valign=\"top\"\u003e\n \u003cp\u003e10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3783783783783785%\" valign=\"top\"\u003e\n \u003cp\u003e61.8 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e72 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e2.6 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.405405405405405%\" valign=\"top\"\u003e\n \u003cp\u003eSirolimus (1\u003csup\u003est\u003c/sup\u003e Gen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003e205 (68.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.474903474903475%\" valign=\"top\"\u003e\n \u003cp\u003e62.7 (9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e69 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e2.8 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.343629343629344%\" valign=\"top\"\u003e\n \u003cp\u003e2 (1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.888030888030888%\" valign=\"top\"\u003e\n \u003cp\u003e155 (63.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003e211 (70.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003eFREEDOM, 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.142857142857143%\" valign=\"top\"\u003e\n \u003cp\u003eRCT, superiority\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eDeath, stroke, MI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.177606177606178%\" valign=\"top\"\u003e\n \u003cp\u003eMultivessel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.633204633204633%\" valign=\"top\"\u003e\n \u003cp\u003e7.5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e953\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3783783783783785%\" valign=\"top\"\u003e\n \u003cp\u003e63.2 (8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e255 (26.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e2.7 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.405405405405405%\" valign=\"top\"\u003e\n \u003cp\u003eSirolimus/ Paclitaxel\u003c/p\u003e\n \u003cp\u003e(1\u003csup\u003est\u003c/sup\u003e Gen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e947\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.474903474903475%\" valign=\"top\"\u003e\n \u003cp\u003e63.1 (9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e289 (30.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e2.8 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.343629343629344%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.888030888030888%\" valign=\"top\"\u003e\n \u003cp\u003e165 (18.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;BEST, 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.142857142857143%\" valign=\"top\"\u003e\n \u003cp\u003eRCT, noninferiority\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eDeath, MI, repeat revascularization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.177606177606178%\" valign=\"top\"\u003e\n \u003cp\u003eMultivessel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.633204633204633%\" valign=\"top\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3783783783783785%\" valign=\"top\"\u003e\n \u003cp\u003e64 (9.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e134 (30.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e2.9 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.405405405405405%\" valign=\"top\"\u003e\n \u003cp\u003eEverolimus\u003c/p\u003e\n \u003cp\u003e(2\u003csup\u003end\u003c/sup\u003e Gen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003e236 (50.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.474903474903475%\" valign=\"top\"\u003e\n \u003cp\u003e64.9 (9.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e117 (26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e3 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.343629343629344%\" valign=\"top\"\u003e\n \u003cp\u003e2 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.888030888030888%\" valign=\"top\"\u003e\n \u003cp\u003e258 (64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003e274 (71.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003eNOBLE, 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.142857142857143%\" valign=\"top\"\u003e\n \u003cp\u003eRCT, noninferiority\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eDeath, stroke, MI, repeat revascularization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.177606177606178%\" valign=\"top\"\u003e\n \u003cp\u003eLM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.633204633204633%\" valign=\"top\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e592\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3783783783783785%\" valign=\"top\"\u003e\n \u003cp\u003e66.2 (9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e116 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.405405405405405%\" valign=\"top\"\u003e\n \u003cp\u003eBiolimus (2\u003csup\u003end\u003c/sup\u003e Gen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003e543 (94.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e592\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.474903474903475%\" valign=\"top\"\u003e\n \u003cp\u003e66.2 (9.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e140 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003e2 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.343629343629344%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.888030888030888%\" valign=\"top\"\u003e\n \u003cp\u003e88 (15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003eEXCEL, 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.142857142857143%\" valign=\"top\"\u003e\n \u003cp\u003eRCT, noninferiority\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eDeath, stroke, MI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.177606177606178%\" valign=\"top\"\u003e\n \u003cp\u003eLM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.633204633204633%\" valign=\"top\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e948\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3783783783783785%\" valign=\"top\"\u003e\n \u003cp\u003e66 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e226 (23.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.405405405405405%\" valign=\"top\"\u003e\n \u003cp\u003eEverolimus (2\u003csup\u003end\u003c/sup\u003e Gen)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.9922779922779923%\" valign=\"top\"\u003e\n \u003cp\u003e957\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.474903474903475%\" valign=\"top\"\u003e\n \u003cp\u003e65.9 (9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.44015444015444%\" valign=\"top\"\u003e\n \u003cp\u003e215 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.7915057915057915%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.343629343629344%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.888030888030888%\" valign=\"top\"\u003e\n \u003cp\u003e271 (29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.397683397683398%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Percutaneous Coronary Intervention, drug eluting stent, coronary artery bypass grafting, female, male, sex","lastPublishedDoi":"10.21203/rs.3.rs-4637921/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4637921/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDespite the advances in the last decades for treatment of ischemic heart disease, women continue to experience poorer prognosis than men and currently, there is a gap in knowledge regarding the optimal revascularization strategy in women.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eCompare the long-term outcomes of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for the treatment of stable ischemic heart disease in women.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA systematic search was conducted including randomized clinical trials (RCTs) comparing PCI with drug-eluting stents with CABG. The primary outcome were the composite outcomes of death, stroke or myocardial infarction (MI) and death, stroke, MI or repeat revascularization. Secondary outcomes included the individual components of the primary outcomes. Pooled hazard ratios with 95% confidence intervals were calculated in a fixed- effects meta-analysis using the inverse of variance method. Risk of bias and sensitivity analyses were also conducted.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSix multicenter, RCTs were included after eligibility assessment. Median follow-up was 6.25 years (IQR: 5- 2.5). A significant benefit for CABG over PCI was observed for the primary composite outcomes of death, stroke, MI (HR\u0026thinsp;=\u0026thinsp;1.24; 95% CI 1.01\u0026ndash;1.52; p\u0026thinsp;=\u0026thinsp;0.037) and death, stroke, MI or repeat revascularization (HR\u0026thinsp;=\u0026thinsp;1.60; 95% CI 1.25\u0026ndash;2.03; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn the present study-level metanalysis, CABG is associated with a lower risk of major adverse cardiovascular events than PCI at long term follow-up in women.\u003c/p\u003e","manuscriptTitle":"Long-term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting in women, a meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-23 22:03:52","doi":"10.21203/rs.3.rs-4637921/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-08T18:07:32+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-27T09:58:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-11T14:23:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-10T20:40:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"122001401844002271990012546851876135234","date":"2024-08-06T02:42:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"226585755583857040168722891887367648078","date":"2024-08-04T19:21:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"288670611413431106652751571491104617022","date":"2024-08-04T19:09:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"52338287223882300056419824603311165874","date":"2024-08-02T21:26:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-02T18:56:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-01T12:42:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-01T12:42:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cardiothoracic Surgery","date":"2024-06-25T16:40:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4c8508ca-18fb-46c6-8fdb-471fa6a5c4d3","owner":[],"postedDate":"July 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-23T16:04:19+00:00","versionOfRecord":{"articleIdentity":"rs-4637921","link":"https://doi.org/10.1186/s13019-024-03167-y","journal":{"identity":"journal-of-cardiothoracic-surgery","isVorOnly":false,"title":"Journal of Cardiothoracic Surgery"},"publishedOn":"2024-12-20 15:58:04","publishedOnDateReadable":"December 20th, 2024"},"versionCreatedAt":"2024-07-23 22:03:52","video":"","vorDoi":"10.1186/s13019-024-03167-y","vorDoiUrl":"https://doi.org/10.1186/s13019-024-03167-y","workflowStages":[]},"version":"v1","identity":"rs-4637921","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4637921","identity":"rs-4637921","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}