Stents versus Bypass Surgery – 3-Year Mortality Risk of Patients with Coronary Interventions Aged 50+ in Germany

Stents versus Bypass Surgery – 3-Year Mortality Risk of Patients with Coronary Interventions Aged 50+ in Germany | 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 Stents versus Bypass Surgery – 3-Year Mortality Risk of Patients with Coronary Interventions Aged 50+ in Germany Sophia Nestler, Daniel Kreft, Peter Donndorf, Hüseyin Ince, Gabriele Doblhammer This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1366225/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Objectives Due to demographic aging, the prevalence of coronary artery disease (CAD) is expected to increase in the future, resulting in a growing demand for stent and bypass interventions. This study aims to investigate the mortality risk of patients following conventional coronary artery bypass grafting (CABG) or endovascular procedure by the implantation of bare-metal stents (BMS) or drug-eluting stents (DES). Methods Based on a random sample of 250,000 members of Germany’s largest health insurance ‘Allgemeine Ortskrankenkassen’ (AOK) from 2004 to 2015, incident CAD patients were analyzed by Cox Proportional-Hazard models. Risk adjustment was made for sex, age, other cardiac diseases, non-cardiovascular comorbidities and years since intervention. Due to later admission of DES and thus a shorter observation time, mortality was examined for 3 years since the intervention. Results BMS represented the most frequent procedure (48%). We found similar proportions of CABG (19%) and DES interventions (23%). After risk adjustment, the models showed a 21% (p=0.004) lower mortality risk of patients with DES and also a 21% (p=0.002) lower mortality risk of CABG patients compared to persons with BMS. Conclusion Based on a large-scale dataset, our study demonstrated survival advantages of CABG and DES interventions over BMS, with no differences between the DES and CABG groups. The results help to assess the risks of coronary interventions. Aspects of quality of life, severity of postoperative physical limitations, duration of rehabilitation, patients’ preferences, and aspects of cost-effectiveness for hospitals and society should be further considered. coronary artery disease stents coronary artery bypass health claims data follow-up mortality Figures Figure 1 Figure 2 Introduction Coronary artery disease (CAD) is the leading cause of death worldwide. Globally, ischemic heart diseases caused 8.9 out of 55.5 million deaths between 1980 and 2015 (16%) and 15.2 million people deceased due to ischemic heart disease and stroke (27%) [ 1 ]. Thus, improvements in medicine and technology are essential in future gains in longevity and quality of life at the oldest ages. Considering the demographic characteristics of patients, the incidence of CAD increases with age. Men show a higher prevalence and are also more likely to receive coronary interventions as women. CAD is perceived as a male-dominated disease; however, it is the leading cause of death in women aged 65 years and older worldwide. In this context, it is important to consider that ischemic heart diseases in women often progress asymptomatically, which results in delays of medical treatment [ 2 ]. In the last two decades percutaneous coronary interventions (PCI) with stent implantation emerged as alternative to surgical procedure of coronary artery bypass grafting (CABG) in the treatment of CAD. This trend is particularly evident in Germany: in 2003 the ALKK (“Arbeitsgemeinschaft leitender kardiologischer Krankenhausärzte”) registry reported approximately 30,000 cases of PCI with stent [ 3 ]. However, in 2015 more than 300,000 PCI’s compared to 50,000 procedures of CABG proceeded whereby drug-eluting stents (DES) accounted for 91.2% of revascularizations [ 4 ]. Recent findings of comparing the efficacy and safety of coronary stents preferred innovative DES over traditional bare-metal stents (BMS) in terms of a lower incidence of adverse cardiac events leading to death [ 5 ]. Thus, we hypothesized survival benefits of DES towards BMS within the first three years since patients underwent initial coronary intervention (Hypothesis I). According to short-term follow-ups of patients with coronary interventions, stent implantation potentially revealed lower mortality rates compared to CABG (Hypothesis II) [ 6 ]. However, considering the mortality selection shortly after revascularization procedure, we expected CABG to be associated with a higher 3-year-survival compared to DES (Hypothesis III). The role and benefits of CABG in the treatment of a specific subtype of CAD, namely complex multivessel disease, were well established in the recent past by long term clinical follow up and landmark studies such as the SYNTAX trial. The outcome following PCI or CABG in patients exhibiting left main stem disease was addressed by several trials such as the EXEL trial and the NOBLE trial. These trials reported non-inferiority of PCI in the treatment of left main stem disease but with persistent advantages for CABG in terms of the need for repeated revascularization during follow-up [ 7 , 8 ]. Contrary to previous studies, our sample was not biased by health selection of respondents. We compared survival after stent- and bypass procedure to mortality in CAD patients who never underwent coronary intervention and also provided the disease duration of CAD. Thus, we represented a valid ‘real-world analysis’ of clinical results following different types of coronary revascularization in a large patient cohort. Our study complied with RECORD reporting guidelines, which were developed for studies involving routinely collected health data. As an extension of the existing STROBE guidelines, we fulfilled the RECORD reporting requirements by adequately conveying the methods and results of our research. Materials And Methods Data source Our analysis based on anonymized routine data from the largest public health insurance ‘Allgemeine Ortskrankenkassen’ (AOK) in Germany. The scientific institute of the AOK (WIdO) granted the data access. The random sample consisted of 250,000 members from private households and nursing homes which aged 50 + years, and we tracked from first quarter in 2004 until fourth quarter in 2015 at the latest. The routine data covered patients’ sex, date of birth and death, as well as in- and outpatient diagnoses coded by the Operational and Procedural Classification (OPS), and the International Classification of Diseases and Related Health Problems (ICD-10-GM). The data also comprised a unique identification number and only involved completely anonymized information. Thus, the study complied with the tenets of the Declaration of Helsinki and did not require an ethical approval. Definition of outcome measure and risk factors The mortality status based on master data of health claims. In analysis, we set the time of death to the middle of the month of death. We included BMS coded by OPS as ‘8-837.k’ and DES coded as ‘8-837.m’. For CABG we considered OPS-codes ‘5-361*’ and ‘5-362*’. We categorized the variable of intervention type into “BMS”, “DES”, “CABG”, “mixed”, and “none” (no procedure). The categories BMS, DES and CABG implied initial interventions, whereas patients in the mixed-group underwent at least two different revascularization techniques in one quarter or received different intervention types as a re-intervention. Patients remained in ‘none’ as long as they did not receive BMS, DES, or CABG. Intergroup changes from none to BMS, DES, CABG or mixed and from BMS, DES or CABG to mixed were possible. Control variables and validation strategy Analysis controlled for sex, and age at first valid CAD diagnosis or at first coronary intervention (50–54, 55–59, 60–64, 65–69, 70–74, 75–79, 80–84, 85+). To identify modifying effects of other cardiac diseases on mortality, we included the following ICD-10-diagnoses ever received between 2004 and 2015: acute coronary syndrome (I21 and I20.0), congestive heart failure (I09.9, I11.0, I13.0, I13.2, I25.5, I42.0, I42.5-I42.9, I43, I50), cardiogenic shock (R57.0), arrhythmia (I44.1-I44.3, I45.6, I45.9, I46, I47, I48, I49, R00.0, R00.1, R00.8, T82.1, Z45.0, Z95.0), multivessel coronary artery disease (I25.13). We also considered non-cardiovascular diseases with high impact on mortality. We measured the risk factor “multimorbidity” by an additive score as the number of the following acute and chronic diseases ever diagnosed between 2004 and 2015: atherosclerosis (I70), Alzheimer’s disease (F00), diabetes mellitus (I10-I14), cancer (C00-C97), liver diseases (B18, K70-K72, K76, Z94.4), lung diseases (J44, J47), neurological diseases (G00-G09, G23, G24-G26, G31.8, G32), kidney diseases (N17-N19, Z94.2, T82.4, Z99.2), Parkinson’s disease (G20-G22), cerebrovascular diseases (I60-I69, G45, G46, H34), paralysis (G80-G83, G04.1, G11.4) and peptic ulcer (K25-K28). The multimorbidity score consisted three categories: 0–1, 2–6, or 7 + of the selected diseases. In addition, we considered external injuries (S00-S03, T00, T01.3, T02.4, T02.6-T02.9, T05.8, T05.9, T14-T98) as non-degenerative risk factor of death. All diseases were defined as irreversible since the first observed diagnosis. Another control variable concerned the duration since coronary intervention measured in years. We compared CAD patients in 1st to 2nd year since intervention with a third (residual) group that covered both, CAD patients in the 3rd year and CAD patients who never received BMS, DES, or CABG. We reduced the problem of false-positive CAD diagnoses by applying a validation strategy: to define the first CAD diagnosis as valid, the patient required the co-occurrence of CAD diagnosis in another quarter over the whole observation period [ 9 ]. We considered all covariates, with the exception of sex and age at incident CAD diagnosis, to be time-varying variables with value 1 since first valid diagnosis and 0 otherwise Sample selection First, we excluded all patients with inconsistent or implausible information of birth or death (n = 463) and 7 332 persons under the age of 50 (Fig. 1). To only include incident CAD cases, patients with CAD diagnosis already underlying in 2004 (n = 16 366) met the exclusion criteria. Considering deceased and patients who left the AOK in 2004, the sample decreased by 9 395 persons. We further excluded patients with first CAD diagnosis in 2015 (n = 2 782) to avoid an end-of-study-bias, and those who had less than three years of follow-up after initial intervention as of Q1 2013 (n = 1 324), just as patients with an incident CAD diagnosis and death in the same quarter (n = 2 447). The final study cohort comprised 39 418 incident CAD patients without or with coronary intervention between Q1 2005 and Q4 2012. Statistical analysis We estimated sex and age-standardized 3-year mortality rates from 2005 to 2015 by using the German average population of 2005 and computed the mortality rate for each intervention type by dividing the number of deaths ( \({D}_{2005-15,x,a}\) ) by the population under risk (Equ. 1). The Person-years under risk ( \({PY}_{Risk}\) ) from 2005 to 2015 defined the population of risk in the denominator. \({Mortality}_{2005-15,x,a}=\frac{{D}_{2005-15,x,a}}{{PY}_{Risk2005-15,x,a}}*100\) (Equ. 1) To compare 3-year survival after coronary intervention, we applied Kaplan-Meier estimators. We also computed Cox proportional-hazard models, which aimed to examine disparities in the 3-year mortality among CAD patients with adjustment for demographic characteristics, cardiovascular and non-cardiac diseases and the years passed since intervention. In sensitivity analysis, we calculated an additional model excluding CAD patients who never underwent coronary intervention in the observation period, as well as the observation time prior to intervention. All analyses were conducted with the use of Stata (version 16.1). We measured analysis time as the years since first valid CAD diagnosis as of Q1 2005 at the earliest (Figure S1, persons 1–5). Following the principles of Hernán et al. (2016) and Emilson et al. (2018), we emulated a target trial [ 10 , 11 ]. We maximally tripled all eligible observations (measured in person-times) and assigned each copy to the corresponding coronary intervention group (none, BMS, DES, CABG or mixed). In case of a group change we defined a time zero of analysis time (Figure S1, persons 1 & 2). Coronary intervention simultaneous with the first valid CAD diagnosis (study entry) was also possible (Figure S1, persons 3 & 5). To face the immortal time bias, we censored CAD patients after a follow-up of 3 years spend in the category of BMS, DES or CABG (Figure S1, persons 2, 3 & 5). Person-times spend in the categories of none and mixed had no observational time limit (Figure S1, person 4). Results Patients at CAD diagnosis and death 12 974 out of 39 418 incident CAD patients died (Table 1 ) and we found that 1 245 of the deceased underwent coronary revascularization (Table 2 ). 48.22% of patients with coronary intervention received a BMS, whereas 45.94% of the deceased were assigned to the same group. 22.64% of CAD patients received DES and 18.77% underwent bypass surgery. Mortality in patients with CABG (18.80%) was slightly higher than in patients with DES (17.35%). A total of 754 (10.38%) persons had mixed intervention types. The mixed group consisted of 371 (49.20%) initial revascularizations and 383 (50.80%) re-interventions with changed intervention type. The sample revealed a balanced representation of females and males at first CAD diagnosis (50.13% and 49.87%) and among the deceased (47.39% and 52.61%, Table 1 ). With increasing age, the number of CAD diagnoses increased as well as mortality. 20.74% received their first CAD diagnosis in the age of 70–74, whereas mortality reached a peak at ages 85 and older (24.87%). Considering the other ischemic heart diseases at study entry, acute coronary syndrome was diagnosed in 27.98% and almost half of the insured (46.12%) had congestive heart failure. Cardiogenic shock affected 2.22% of patients and we found a prevalence of 52.37% for arrhythmia. 28.70% suffered from multivessel coronary artery disease at first CAD diagnosis. Among the deceased, cardiogenic shock showed a five times higher prevalence (11.25%) compared to study entry and patients with congestive heart failure contributed the majority (81.82%). We found arrhythmia in 75.47% whereas diagnoses of acute coronary syndrome (35.37%) and multivessel coronary artery disease (33.77%) concerned approximately one third of deaths. Table 1 Descriptive overview of CAD patients at study entry and death, 2005–2015. Persons at CAD diagnosis Deaths 2005–2015 n % n % Sex Males 19 760 50.13 6 149 47.39 Females 19 658 49.87 6 825 52.61 Age at CAD diagnosis / coronary intervention 50–54 501 1.27 63 0.49 55–59 2 366 6.00 277 2.14 60–64 4 144 10.51 556 4.29 65–69 6 051 15.35 1 175 9.06 70–74 8 175 20.74 2 032 15.66 75–79 7 664 19.44 2 693 20.76 80–84 5 969 15.14 2 951 22.75 85+ 4 548 11.54 3 227 24.87 Acute coronary syndrome No 28 389 72.02 8 366 64.48 Yes 11 029 27.98 4 608 35.52 Congestive heart failure No 21 240 53.88 2 359 18.18 Yes 18 178 46.12 10 615 81.82 Cardiogenic shock No 38 541 97.78 11 515 88.75 Yes 877 2.22 1 459 11.25 Arrhythmia No 18 775 47.63 3 183 25.53 Yes 20 643 52.37 9 791 75.47 Multivessel coronary artery disease No 28 106 71.30 8 593 66.23 Yes 11 312 28.70 4 381 33.77 Comorbidities 0 to 1 3 283 8.33 500 3.85 2 to 6 30 076 76.30 9 927 76.51 7 to 12 6 059 15.37 2 547 19.63 External injuries No 30 610 77.65 9 343 72.01 Yes 8 808 22.35 3 631 27.99 Years since intervention First year 6 880 28.70 518 3.99 Second year - - 354 2.73 Third year / no intervention 32 538 71.30 12 102 93.28 Total 39 418 100% 12 974 100% Table 2 Coronary interventions 2005–2012 and deaths 2005–2015. Coronary interventions 2005–2012 Deaths 2005–2015 n % n % BMS 3 502 48.22 572 45.94 DES 1 644 22.64 216 17.35 CABG 1 363 18.77 234 18.80 mixed 754 a 10.38 223 17.91 Total 7 263 100% 1 245 100% a including 371 (49.20%) initial coronary interventions and 383 (50.80%) re-interventions with changed intervention type Most patients had at least two to six additional diseases independent from cardiac diseases at study entry (76.30%) and death (76.51%). 22.35% were affected by external injuries at first valid CAD diagnosis and 27.99% of patients at death. 6 880 (28.70%) had initial revascularization at first CAD diagnosis. Among the deceased, 93.28% never received coronary intervention, or intervention was more than three years ago. 2.73% of deaths occurred in the second year since intervention whereas 3.99% of patients died in the first year. The descriptive overview of coronary interventions per patient (2005–2012) and subsequent deaths (2005–2015) contained initial interventions as well as re-interventions with same and changed intervention type (Tab. S1). 78.44% received one intervention. 16.98% underwent a second intervention whereas 3.62% obtained a third re-vascularization. The number of coronary interventions per person varied between one and seven. CAD patients with four and more interventions represented less than 1% of the sample. Survival in CAD patients Without risk adjustment, the survival curves of BMS, CABG, mixed and none overlapped within the first year since coronary intervention (Fig. 2, Tab. S2), whereas after one year, DES patients showed a higher survival (DES: 96.31%) compared to BMS (93.99%); CABG (94.12%) or the none group (91.65%). With progressing time, the survival curves revealed disparities in mortality risk. Whereas CABG implied higher mortality compared to BMS, DES and none after the first year since intervention, CABG had survival advantage over BMS and none (CABG: 91.19%; BMS: 89.42%; none: 84.87%) after the second year as well as after the third year (CABG: 88.71%; BMS: 84.99%; none: 79.54) and converged to the curve of DES. We found worse survival outcomes for CAD patients without coronary intervention. Three years after CAD diagnosis just over two thirds of the none group were still alive. The Log-rank test indicated non-equality of survivor functions (p < 0.001). Within the first three years after intervention, mortality rates increased with increasing age of patient but there was no sex difference by intervention type (Fig. S2). Mortality rates of CAD patients without revascularization also showed no significant sex disparities. Multivariable analysis Controlled for sex, age at first CAD diagnosis or coronary intervention, cardiovascular and non-cardiac diseases as well as the years since intervention, mortality in patients without stent or bypass surgery was 60% (p < 0.001) higher compared to any intervention type (Table 3 ). DES patients showed 21% (p = 0.004) lower mortality risk as the BMS group. We also observed survival benefits of CABG (HR: 0.79; CI: 0.68–0.92; p = 0.002) towards BMS patients. In sensitivity analysis (Tab. S3), the HR for DES (HR: 0.77; CI: 0.66–0.90; p = 0.001) and CABG (HR: 0.68; CI: 0.58–0.80; p < 0.001) even decreased as compared to the total model, indicating that the effects of coronary interventions were not driven by mortality pattern of the CAD patients without BMS, DES, or CABG. Table 3 Multivariable analysis of risk factors effecting mortality in CAD patients, 2005-2015 a . Hazard Ratio (95% CI) p-value Coronary intervention (Reference: BMS) none 1.60 ( 1.41 - 1.82 ) p < 0.001 DES 0.79 ( 0.68 - 0.93 ) 0.004 CABG 0.79 ( 0.68 - 0.92 ) 0.002 mixed 0.81 ( 0.69 - 0.94 ) 0.007 (n = 39 418; deaths = 12 974; LR = 12 032.08; p < 0.001) a Cox model controlled for sex, age at CAD diagnosis / coronary intervention, cardiovascular and non-cardiac diseases, years since intervention Discussion DES and CABG showed similar survival advantages in 3-year mortality follow-up which based on a large number of CAD patients. Among the different operative procedures, BMS indicated worse results but worst survival outcomes we found for CAD patients who never underwent coronary intervention. The descriptive results also confirmed a more frequently application of stents compared to bypass surgery. Thus, we are able to replicate the findings of earlier studies but extended them to a longer follow-up period and used a larger sample size with higher representativity of the general population. When interpreting the results of our study it is important to consider that the analysis included various types of CAD morphology. Earlier studies showed disparities in survival outcomes between DES and CABG for specific CAD profiles. With the adjustment for risk factors of death in multivariable analysis, the tendency of DES to be superior over CABG in Kaplan-Meier estimates ceased. The survival curves implied a higher postoperative mortality risk of open-surgical procedure in first year after intervention compared to catheter-based revascularization, but also showed the long-term benefit of CABG after 3 years of follow-up. Our study confirmed non-inferiority for DES as compared to CABG and thus indicated favorable results for aging populations with high burden of ischemic heart disease. However, the equality of survival outcomes for DES and CABG possibly emerged due to the healthier and younger CAD patients who received bypass surgery. On the other hand, it can be estimated that less complex CAD, i.e. one- and two vessel disease, was preferentially treated by DES regardless patients age. High mortality in patients who never received coronary intervention can be caused by a delayed first diagnosis of CAD, a general worse health profile or patient’s preferences to reject an operative procedure. Furthermore, our study revealed less expected results. Patients with BMS showed worse survival outcomes as compared to DES or CABG. Nevertheless, BMS represents the most frequent procedure used between 2005 and 2012. According to the current state of medical research, the BMS can be seen as historical in clinical importance. Hence, there is seldom a compelling reason to prefer BMS to DES [ 12 ]. Drug-eluting stents were developed to improve the long-term efficacy and safety of patients receiving percutaneous coronary interventions and hitherto represents the gold standard in interventional CAD treatment [ 13 ]. Given the generally higher number of deaths in male CAD patients, the missing sex-gradient in mortality in our study supports earlier studies that point towards a more severe progression of disease in women due to a delayed first CAD diagnosis. Prospective clinical trials demonstrated clinical advantages regarding survival and/or subsequent cardiac events for either treatment method depending on specific CAD morphologies, e.g. isolated left main stenosis or three-vessel disease [ 14 ]. A large retrospective study by Head et al. (2018) analyzed differences in mortality following PCI or CABG in patients with multivessel-disease and left main stem stenosis. Similar to the mentioned prospective clinical trials this pooled analysis of individual patient data found a mortality benefit for CABG over PCI in patients with multivessel-disease whereas no benefit for CABG over PCI was seen in left main disease [ 15 ]. The strength and main clinical impact of the retrospective results presented here is that data were obtained from a large patient cohort without pre-specifying for certain coronary morphologies including even one- and two-vessel disease. In this way our data provided a unique validation of early and midterm survival following invasive CAD treatment on an observational basis in “a real-world scenario and matched the overall survival results following PCI or CABG performed within prospective clinical trials. Strengths And Limitations An important advantage of this health claims analysis was the large sample size concerning the number of CAD patients and different coronary interventions, just as the range of diagnoses from all fields of medicine. Also, the cohort design offered a long observation period of twelve years to track patient’s health status and changes over time. We reduced false-positive diagnoses of CAD by using a validation strategy and assumed high validity of the diagnoses, which based on medical examinations of practicing physicians, and the interventions because health claims data aims to document medical treatments and their costs. The elimination of false-negative CAD diagnoses was possible due to the wash-out period in 2004 but came up again when patients received their second diagnosis of coronary artery disease after 2014. Another limitation concerned that our data based on all-cause mortality and was limited to medical or demographic risk factors of death. Also, the patient’s preferences have to be considered, who often favor a less invasive treatment strategy. In contrast to clinical trials, our official process-generated data source (‘AOK’) was not affected by self-selected dropouts, reactivity (e.g. social desirability), any response biases and any cognitive biases (e.g. recall bias or overconfidence bias). To solve three general problems of observational studies: The mortality selection bias, the end-of-study-bias, and the immortal time bias, we opposed the biases by emulating a randomized target trial following pre-defined eligibility criteria [ 10 ]. Conclusion Our results strengthened the interdisciplinary approach in treating CAD patients by either percutaneous coronary intervention using DES or CABG are clearly demonstrated to represent complementary rather than competing treatment options. An early survival benefit of PCI using DES is supplemented by an advantage of CABG regarding the mid and long-term survival. Similar to the treatment of structural heart disease, institutional Heart Teams consisting of cardiac surgeons and cardiologists should evaluate CAD cases on a routine basis and allocate patients to the optimal treatment, thereby taking in account patient age, comorbidities and the specific morphology (i.e. single or multi-vessel disease, presence or absence of left main stenosis) of the underlying CAD. There is a need for future long-term observational analyses, such as the one presented here, but with a focus on specific coronary morphologies in order to compare their results of surgical versus interventional CAD treatments in large cohorts of patients. Declarations Acknowledgements We are grateful to Christian Günster from the Scientific Research Institute of the AOK, WIdO, for providing the data. Funding This work was supported by the Federal Ministry of Education and Research, Germany, Grant number 03ZZ0923A. Conflict of interest The authors declare that they have no conflict of interest. Author contribution D.K. and G.D. designed the model and the computational framework. G.D. supervised the work. S.N. performed the calculations and designed the figures and tables. S.N. wrote the original draft. G.D., D.K., P.D., and H.I. reviewed and edited the manuscript with input from all authors. All authors discussed the results and contributed to the final manuscript. Availability of data and material The scientific research institute of the AOK (WIdO) has strict rules regarding data sharing because health claims data are a sensitive data source and have ethical restrictions imposed due to concerns regarding privacy. Anonymized data are available to all interested researchers upon request. Interested individuals or an institution who wish to request access to the health claims data of the AOK may contact the WIdO (webpage: http://www.wido.de/, mail: [email protected] ). References Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. 2016;388:1459–544. doi: 10.1016/S0140-6736(16)31012-1 . Maas AH, Appelman YEA. Gender differences in coronary heart disease. Neth Heart J. 2010;18:598–603. Zeymer U, Zahn R, Hochadel M, Bonzel T, Weber M, Gottwik M, et al. Incications and complications of invasive diagnostic procedures and percutaneous coronary interventions in the year 2003. Z für Kardiologie. 2005;94:392–8. Meinertz T, Hamm C, Schlensak C, Fleck E, Cremer J, Stiller B, et al. Deutscher Herzbericht 2016: 28. Bericht/Sektorenübergreifende Versorgungsanalyse zur Kardiologie, Herzchirurgie und Kinderherzmedizin in Deutschland: Deutsche Herzstiftung; 2017. Babapulle MN, Joseph L, Bélisle P, Brophy JM, Eisenberg MJ. A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents. The Lancet. 2004;364:583–91. Villareal RP, Lee V-V, Elayda MA, Wilson JM. Coronary artery bypass surgery versus coronary stenting: risk-adjusted survival rates in 5,619 patients. Tex Heart Inst J. 2002;29:3. Stone GW, Kappetein AP, Sabik JF, Pocock SJ, Morice M-C, Puskas J, et al. Five-year outcomes after PCI or CABG for left main coronary disease. N Engl J Med. 2019;381:1820–30. Mäkikallio T, Holm NR, Lindsay M, Spence MS, Erglis A, Menown IBA, et al. Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial. The Lancet. 2016;388:2743–52. McGuire TG, van Kleef RC. Risk, Adjustment. Risk Sharing and Premium Regulation in Health Insurance Markets: Theory and Practice. London: Academic Press; 2018. Emilsson L, García-Albéniz X, Logan RW, Caniglia EC, Kalager M, Hernán MA. Examining bias in studies of statin treatment and survival in patients with cancer. JAMA Oncol. 2018;4:63–70. Hernán MA, Sauer BC, Hernández-Díaz S, Platt R, Shrier I. Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses. J Clin Epidemiol. 2016;79:70–5. Ariotti S, Adamo M, Costa F, Patialiakas A, Briguori C, Thury A, et al. Is bare-metal stent implantation still justifiable in high bleeding risk patients undergoing percutaneous coronary intervention? A pre-specified analysis from the ZEUS trial. JACC: Cardiovasc Interventions. 2016;9:426–36. Puranik AS, Dawson ER, Peppas NA. Recent advances in drug eluting stents. Int J Pharm. 2013;441:665–79. Thuijs DJ, Kappetein AP, Serruys PW, Mohr F-W, Morice M-C, Mack MJ, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial. The Lancet. 2019;394:1325–34. Head SJ, Milojevic M, Daemen J, Ahn J-M, Boersma E, Christiansen EH, et al. Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. The Lancet. 2018;391:939–48. Supplementary Files VisualAbstract.jpg FigureS1.pdf FigureS2.pdf SupplementarytablesS1toS3.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 18 Jun, 2022 Reviewers invited by journal 18 Jun, 2022 Editor assigned by journal 18 Feb, 2022 First submitted to journal 16 Feb, 2022 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1366225","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":114580693,"identity":"e6125262-f4aa-44b2-84ea-5473e235f73e","order_by":0,"name":"Sophia Nestler","email":"","orcid":"","institution":"Universitat Rostock","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sophia","middleName":"","lastName":"Nestler","suffix":""},{"id":114580694,"identity":"8d4bd217-d204-48fa-98ce-4f82ac3eccc2","order_by":1,"name":"Daniel Kreft","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIie3PMUvDQBTA8XcUkuWR+YoFv8ILBxEhtl+lEMgUrZNklUBcCq7x21y4weW0aweHQiFThwOXDg5eCAGHM64O9yfTy/14dwA+339M9t89EAA7gAHA8YedrCcI9Qdm8WMzEvkHgZFU+GP6K4le31ppCMTVUxUeb+qPBVwo9WnKpYAwky4y13frtiFIFlqx6rbuEKI851JnCWDnXEOyIIUEKeeb1hKFK40JtLVMgRfkJLsTqa+eXB5ZdW0JIAozkI1xkr3dYp+acD5jFRsIcUsSu8X5/Pn+RO2WuOCYsZfte0+CnGudiQA758WiXSHMuUzjJlRgzg9qBThTpiyX8XOYHZxrhrhjFkyc9/l8Pt9032/dXmaQ/3LFAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-5153-0202","institution":"Universitat Rostock","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Kreft","suffix":""},{"id":114580695,"identity":"89c99e99-bdcb-4d8e-ac55-f38b07f60881","order_by":2,"name":"Peter Donndorf","email":"","orcid":"","institution":"Klinikum Karlsburg","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Donndorf","suffix":""},{"id":114580696,"identity":"d31bf266-5568-4809-9247-d5cf6ae9f4e1","order_by":3,"name":"Hüseyin Ince","email":"","orcid":"","institution":"Rostock University Medical Center: Universitatsmedizin Rostock","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hüseyin","middleName":"","lastName":"Ince","suffix":""},{"id":114580697,"identity":"913c8faa-6735-42c5-b44d-156d196fbda0","order_by":4,"name":"Gabriele Doblhammer","email":"","orcid":"","institution":"Universitat Rostock","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gabriele","middleName":"","lastName":"Doblhammer","suffix":""}],"badges":[],"createdAt":"2022-02-16 15:14:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1366225/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1366225/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":23016142,"identity":"abd02ecf-3818-4d90-9668-82b5697e4da1","added_by":"auto","created_at":"2022-06-23 18:05:42","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":307435,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of sample selection procedure \u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1366225/v1/73f6e6b01fb08c12ac8bec25.jpg"},{"id":23016141,"identity":"efa72ebc-d0a9-4431-8214-2cf1960bcda8","added_by":"auto","created_at":"2022-06-23 18:05:42","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":33561,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier survival curves by coronary intervention group \u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1366225/v1/65db18f0646031543cd8ea03.jpg"},{"id":23016556,"identity":"2c32e973-c493-4437-bab1-1aeaedc73072","added_by":"auto","created_at":"2022-06-23 18:10:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":461332,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1366225/v1/5ef0e701-ea62-40d1-8ad1-666976a61dc3.pdf"},{"id":23016143,"identity":"a4c75ffd-d718-4941-ae50-efaf86fe60e1","added_by":"auto","created_at":"2022-06-23 18:05:42","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":60140,"visible":true,"origin":"","legend":"","description":"","filename":"VisualAbstract.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1366225/v1/bbe0af9f2560adc9276e5324.jpg"},{"id":23016145,"identity":"3f3cb357-e8a7-4df3-a3ee-81c505218298","added_by":"auto","created_at":"2022-06-23 18:05:42","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":80772,"visible":true,"origin":"","legend":"","description":"","filename":"FigureS1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1366225/v1/abf4c559f02d827ee748e055.pdf"},{"id":23016148,"identity":"829b7d82-a95a-439f-8d85-7b89cbe1a068","added_by":"auto","created_at":"2022-06-23 18:05:42","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":277794,"visible":true,"origin":"","legend":"","description":"","filename":"FigureS2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1366225/v1/b9b2ec79e458bed77278cce6.pdf"},{"id":23016555,"identity":"562d5d9e-f981-4ef6-a5a8-72779bd0e2df","added_by":"auto","created_at":"2022-06-23 18:10:42","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":17355,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementarytablesS1toS3.docx","url":"https://assets-eu.researchsquare.com/files/rs-1366225/v1/52f1da33f8ce8c2de67d4cd0.docx"}],"financialInterests":"","formattedTitle":"Stents versus Bypass Surgery – 3-Year Mortality Risk of Patients with Coronary Interventions Aged 50+ in Germany","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCoronary artery disease (CAD) is the leading cause of death worldwide. Globally, ischemic heart diseases caused 8.9 out of 55.5\u0026nbsp;million deaths between 1980 and 2015 (16%) and 15.2\u0026nbsp;million people deceased due to ischemic heart disease and stroke (27%) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Thus, improvements in medicine and technology are essential in future gains in longevity and quality of life at the oldest ages. Considering the demographic characteristics of patients, the incidence of CAD increases with age. Men show a higher prevalence and are also more likely to receive coronary interventions as women. CAD is perceived as a male-dominated disease; however, it is the leading cause of death in women aged 65 years and older worldwide. In this context, it is important to consider that ischemic heart diseases in women often progress asymptomatically, which results in delays of medical treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the last two decades percutaneous coronary interventions (PCI) with stent implantation emerged as alternative to surgical procedure of coronary artery bypass grafting (CABG) in the treatment of CAD. This trend is particularly evident in Germany: in 2003 the ALKK (\u0026ldquo;Arbeitsgemeinschaft leitender kardiologischer Krankenhaus\u0026auml;rzte\u0026rdquo;) registry reported approximately 30,000 cases of PCI with stent [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, in 2015 more than 300,000 PCI\u0026rsquo;s compared to 50,000 procedures of CABG proceeded whereby drug-eluting stents (DES) accounted for 91.2% of revascularizations [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Recent findings of comparing the efficacy and safety of coronary stents preferred innovative DES over traditional bare-metal stents (BMS) in terms of a lower incidence of adverse cardiac events leading to death [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Thus, we hypothesized survival benefits of DES towards BMS within the first three years since patients underwent initial coronary intervention (Hypothesis I). According to short-term follow-ups of patients with coronary interventions, stent implantation potentially revealed lower mortality rates compared to CABG (Hypothesis II) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, considering the mortality selection shortly after revascularization procedure, we expected CABG to be associated with a higher 3-year-survival compared to DES (Hypothesis III).\u003c/p\u003e \u003cp\u003eThe role and benefits of CABG in the treatment of a specific subtype of CAD, namely complex multivessel disease, were well established in the recent past by long term clinical follow up and landmark studies such as the SYNTAX trial. The outcome following PCI or CABG in patients exhibiting left main stem disease was addressed by several trials such as the EXEL trial and the NOBLE trial. These trials reported non-inferiority of PCI in the treatment of left main stem disease but with persistent advantages for CABG in terms of the need for repeated revascularization during follow-up [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eContrary to previous studies, our sample was not biased by health selection of respondents. We compared survival after stent- and bypass procedure to mortality in CAD patients who never underwent coronary intervention and also provided the disease duration of CAD. Thus, we represented a valid \u0026lsquo;real-world analysis\u0026rsquo; of clinical results following different types of coronary revascularization in a large patient cohort.\u003c/p\u003e \u003cp\u003e Our study complied with RECORD reporting guidelines, which were developed for studies involving routinely collected health data. As an extension of the existing STROBE guidelines, we fulfilled the RECORD reporting requirements by adequately conveying the methods and results of our research.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eData source\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur analysis based on anonymized routine data from the largest public health insurance \u0026lsquo;Allgemeine Ortskrankenkassen\u0026rsquo; (AOK) in Germany. The scientific institute of the AOK (WIdO) granted the data access. The random sample consisted of 250,000 members from private households and nursing homes which aged 50\u0026thinsp;+\u0026thinsp;years, and we tracked from first quarter in 2004 until fourth quarter in 2015 at the latest. The routine data covered patients\u0026rsquo; sex, date of birth and death, as well as in- and outpatient diagnoses coded by the Operational and Procedural Classification (OPS), and the International Classification of Diseases and Related Health Problems (ICD-10-GM). The data also comprised a unique identification number and only involved completely anonymized information. Thus, the study complied with the tenets of the Declaration of Helsinki and did not require an ethical approval.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition of outcome measure and risk factors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mortality status based on master data of health claims. In analysis, we set the time of death to the middle of the month of death.\u003c/p\u003e\n\u003cp\u003eWe included BMS coded by OPS as \u0026lsquo;8-837.k\u0026rsquo; and DES coded as \u0026lsquo;8-837.m\u0026rsquo;. For CABG we considered OPS-codes \u0026lsquo;5-361*\u0026rsquo; and \u0026lsquo;5-362*\u0026rsquo;. We categorized the variable of intervention type into \u0026ldquo;BMS\u0026rdquo;, \u0026ldquo;DES\u0026rdquo;, \u0026ldquo;CABG\u0026rdquo;, \u0026ldquo;mixed\u0026rdquo;, and \u0026ldquo;none\u0026rdquo; (no procedure). The categories BMS, DES and CABG implied initial interventions, whereas patients in the mixed-group underwent at least two different revascularization techniques in one quarter or received different intervention types as a re-intervention. Patients remained in \u0026lsquo;none\u0026rsquo; as long as they did not receive BMS, DES, or CABG. Intergroup changes from none to BMS, DES, CABG or mixed and from BMS, DES or CABG to mixed were possible.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eControl variables and validation strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnalysis controlled for sex, and age at first valid CAD diagnosis or at first coronary intervention (50\u0026ndash;54, 55\u0026ndash;59, 60\u0026ndash;64, 65\u0026ndash;69, 70\u0026ndash;74, 75\u0026ndash;79, 80\u0026ndash;84, 85+). To identify modifying effects of other cardiac diseases on mortality, we included the following ICD-10-diagnoses ever received between 2004 and 2015: acute coronary syndrome (I21 and I20.0), congestive heart failure (I09.9, I11.0, I13.0, I13.2, I25.5, I42.0, I42.5-I42.9, I43, I50), cardiogenic shock (R57.0), arrhythmia (I44.1-I44.3, I45.6, I45.9, I46, I47, I48, I49, R00.0, R00.1, R00.8, T82.1, Z45.0, Z95.0), multivessel coronary artery disease (I25.13).\u003c/p\u003e\n\u003cp\u003eWe also considered non-cardiovascular diseases with high impact on mortality. We measured the risk factor \u0026ldquo;multimorbidity\u0026rdquo; by an additive score as the number of the following acute and chronic diseases ever diagnosed between 2004 and 2015: atherosclerosis (I70), Alzheimer\u0026rsquo;s disease (F00), diabetes mellitus (I10-I14), cancer (C00-C97), liver diseases (B18, K70-K72, K76, Z94.4), lung diseases (J44, J47), neurological diseases (G00-G09, G23, G24-G26, G31.8, G32), kidney diseases (N17-N19, Z94.2, T82.4, Z99.2), Parkinson\u0026rsquo;s disease (G20-G22), cerebrovascular diseases (I60-I69, G45, G46, H34), paralysis (G80-G83, G04.1, G11.4) and peptic ulcer (K25-K28). The multimorbidity score consisted three categories: 0\u0026ndash;1, 2\u0026ndash;6, or 7\u0026thinsp;+\u0026thinsp;of the selected diseases.\u003c/p\u003e\n\u003cp\u003eIn addition, we considered external injuries (S00-S03, T00, T01.3, T02.4, T02.6-T02.9, T05.8, T05.9, T14-T98) as non-degenerative risk factor of death. All diseases were defined as irreversible since the first observed diagnosis.\u003c/p\u003e\n\u003cp\u003eAnother control variable concerned the duration since coronary intervention measured in years. We compared CAD patients in 1st to 2nd year since intervention with a third (residual) group that covered both, CAD patients in the 3rd year and CAD patients who never received BMS, DES, or CABG.\u003c/p\u003e\n\u003cp\u003eWe reduced the problem of false-positive CAD diagnoses by applying a validation strategy: to define the first CAD diagnosis as valid, the patient required the co-occurrence of CAD diagnosis in another quarter over the whole observation period [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. We considered all covariates, with the exception of sex and age at incident CAD diagnosis, to be time-varying variables with value 1 since first valid diagnosis and 0 otherwise\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample selection \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFirst, we excluded all patients with inconsistent or implausible information of birth or death (n\u0026thinsp;=\u0026thinsp;463) and 7 332 persons under the age of 50 (Fig.\u0026nbsp;1). To only include incident CAD cases, patients with CAD diagnosis already underlying in 2004 (n\u0026thinsp;=\u0026thinsp;16 366) met the exclusion criteria. Considering deceased and patients who left the AOK in 2004, the sample decreased by 9 395 persons. We further excluded patients with first CAD diagnosis in 2015 (n\u0026thinsp;=\u0026thinsp;2 782) to avoid an end-of-study-bias, and those who had less than three years of follow-up after initial intervention as of Q1 2013 (n\u0026thinsp;=\u0026thinsp;1 324), just as patients with an incident CAD diagnosis and death in the same quarter (n\u0026thinsp;=\u0026thinsp;2 447). The final study cohort comprised 39 418 incident CAD patients without or with coronary intervention between Q1 2005 and Q4 2012.\u003c/p\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe estimated sex and age-standardized 3-year mortality rates from 2005 to 2015 by using the German average population of 2005 and computed the mortality rate for each intervention type by dividing the number of deaths (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({D}_{2005-15,x,a}\\)\u003c/span\u003e\u003c/span\u003e) by the population under risk (Equ. 1). The Person-years under risk (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({PY}_{Risk}\\)\u003c/span\u003e\u003c/span\u003e) from 2005 to 2015 defined the population of risk in the denominator.\u003c/p\u003e\n\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e \u003cspan class=\"mathinline\"\u003e\\({Mortality}_{2005-15,x,a}=\\frac{{D}_{2005-15,x,a}}{{PY}_{Risk2005-15,x,a}}*100\\)\u003c/span\u003e \u003c/span\u003e (Equ. 1)\u003c/p\u003e\n\u003cp\u003eTo compare 3-year survival after coronary intervention, we applied Kaplan-Meier estimators. We also computed Cox proportional-hazard models, which aimed to examine disparities in the 3-year mortality among CAD patients with adjustment for demographic characteristics, cardiovascular and non-cardiac diseases and the years passed since intervention. In sensitivity analysis, we calculated an additional model excluding CAD patients who never underwent coronary intervention in the observation period, as well as the observation time prior to intervention. All analyses were conducted with the use of Stata (version 16.1).\u003c/p\u003e\n\u003cp\u003eWe measured analysis time as the years since first valid CAD diagnosis as of Q1 2005 at the earliest (Figure S1, persons 1\u0026ndash;5). Following the principles of Hern\u0026aacute;n et al. (2016) and Emilson et al. (2018), we emulated a target trial [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. We maximally tripled all eligible observations (measured in person-times) and assigned each copy to the corresponding coronary intervention group (none, BMS, DES, CABG or mixed). In case of a group change we defined a time zero of analysis time (Figure S1, persons 1 \u0026amp; 2). Coronary intervention simultaneous with the first valid CAD diagnosis (study entry) was also possible (Figure S1, persons 3 \u0026amp; 5). To face the immortal time bias, we censored CAD patients after a follow-up of 3 years spend in the category of BMS, DES or CABG (Figure S1, persons 2, 3 \u0026amp; 5). Person-times spend in the categories of none and mixed had no observational time limit (Figure S1, person 4).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec14\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients at CAD diagnosis and death\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e12 974 out of 39 418 incident CAD patients died (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) and we found that 1 245 of the deceased underwent coronary revascularization (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). 48.22% of patients with coronary intervention received a BMS, whereas 45.94% of the deceased were assigned to the same group. 22.64% of CAD patients received DES and 18.77% underwent bypass surgery. Mortality in patients with CABG (18.80%) was slightly higher than in patients with DES (17.35%). A total of 754 (10.38%) persons had mixed intervention types. The mixed group consisted of 371 (49.20%) initial revascularizations and 383 (50.80%) re-interventions with changed intervention type.\u003c/p\u003e\n \u003cp\u003eThe sample revealed a balanced representation of females and males at first CAD diagnosis (50.13% and 49.87%) and among the deceased (47.39% and 52.61%, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). With increasing age, the number of CAD diagnoses increased as well as mortality. 20.74% received their first CAD diagnosis in the age of 70\u0026ndash;74, whereas mortality reached a peak at ages 85 and older (24.87%). Considering the other ischemic heart diseases at study entry, acute coronary syndrome was diagnosed in 27.98% and almost half of the insured (46.12%) had congestive heart failure. Cardiogenic shock affected 2.22% of patients and we found a prevalence of 52.37% for arrhythmia. 28.70% suffered from multivessel coronary artery disease at first CAD diagnosis. Among the deceased, cardiogenic shock showed a five times higher prevalence (11.25%) compared to study entry and patients with congestive heart failure contributed the majority (81.82%). We found arrhythmia in 75.47% whereas diagnoses of acute coronary syndrome (35.37%) and multivessel coronary artery disease (33.77%) concerned approximately one third of deaths.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDescriptive overview of CAD patients at study entry and death, 2005\u0026ndash;2015.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ePersons at CAD diagnosis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDeaths 2005\u0026ndash;2015\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMales\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemales\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 658\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 825\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eAge at CAD diagnosis / coronary intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u0026ndash;54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e501\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u0026ndash;59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 366\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e277\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u0026ndash;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e556\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65\u0026ndash;69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70\u0026ndash;74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75\u0026ndash;79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 664\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 693\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80\u0026ndash;84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 969\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 951\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 548\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eAcute coronary syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 389\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 366\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 608\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eCongestive heart failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 359\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 615\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCardiogenic shock\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38 541\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 515\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e877\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eArrhythmia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 775\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 643\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 791\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eMultivessel coronary artery disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 593\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 381\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eComorbidities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 to 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 283\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 to 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 927\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 to 12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 547\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eExternal injuries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 610\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 343\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 631\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eYears since intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eFirst year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 880\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e518\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eSecond year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eThird year / no intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32 538\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e39 418\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e100%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e12 974\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e100%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCoronary interventions 2005\u0026ndash;2012 and deaths 2005\u0026ndash;2015.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCoronary interventions 2005\u0026ndash;2012\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDeaths 2005\u0026ndash;2015\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 502\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e572\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 644\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCABG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 363\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e754\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e7 263\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e100%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 245\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e100%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003eincluding 371 (49.20%) initial coronary interventions and 383 (50.80%) re-interventions with changed intervention type\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n \u003cp\u003eMost patients had at least two to six additional diseases independent from cardiac diseases at study entry (76.30%) and death (76.51%). 22.35% were affected by external injuries at first valid CAD diagnosis and 27.99% of patients at death. 6 880 (28.70%) had initial revascularization at first CAD diagnosis. Among the deceased, 93.28% never received coronary intervention, or intervention was more than three years ago. 2.73% of deaths occurred in the second year since intervention whereas 3.99% of patients died in the first year.\u003c/p\u003e\n \u003cp\u003eThe descriptive overview of coronary interventions per patient (2005\u0026ndash;2012) and subsequent deaths (2005\u0026ndash;2015) contained initial interventions as well as re-interventions with same and changed intervention type (Tab. S1). 78.44% received one intervention. 16.98% underwent a second intervention whereas 3.62% obtained a third re-vascularization. The number of coronary interventions per person varied between one and seven. CAD patients with four and more interventions represented less than 1% of the sample.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eSurvival in CAD patients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWithout risk adjustment, the survival curves of BMS, CABG, mixed and none overlapped within the first year since coronary intervention (Fig.\u0026nbsp;2, Tab. S2), whereas after one year, DES patients showed a higher survival (DES: 96.31%) compared to BMS (93.99%); CABG (94.12%) or the none group (91.65%). With progressing time, the survival curves revealed disparities in mortality risk. Whereas CABG implied higher mortality compared to BMS, DES and none after the first year since intervention, CABG had survival advantage over BMS and none (CABG: 91.19%; BMS: 89.42%; none: 84.87%) after the second year as well as after the third year (CABG: 88.71%; BMS: 84.99%; none: 79.54) and converged to the curve of DES. We found worse survival outcomes for CAD patients without coronary intervention. Three years after CAD diagnosis just over two thirds of the none group were still alive. The Log-rank test indicated non-equality of survivor functions (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003cdiv class=\"Section2\" id=\"Sec16\"\u003e\n \u003cp\u003eWithin the first three years after intervention, mortality rates increased with increasing age of patient but there was no sex difference by intervention type (Fig. S2). Mortality rates of CAD patients without revascularization also showed no significant sex disparities.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eMultivariable analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eControlled for sex, age at first CAD diagnosis or coronary intervention, cardiovascular and non-cardiac diseases as well as the years since intervention, mortality in patients without stent or bypass surgery was 60% (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) higher compared to any intervention type (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). DES patients showed 21% (p\u0026thinsp;=\u0026thinsp;0.004) lower mortality risk as the BMS group. We also observed survival benefits of CABG (HR: 0.79; CI: 0.68\u0026ndash;0.92; p\u0026thinsp;=\u0026thinsp;0.002) towards BMS patients. In sensitivity analysis (Tab. S3), the HR for DES (HR: 0.77; CI: 0.66\u0026ndash;0.90; p\u0026thinsp;=\u0026thinsp;0.001) and CABG (HR: 0.68; CI: 0.58\u0026ndash;0.80; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) even decreased as compared to the total model, indicating that the effects of coronary interventions were not driven by mortality pattern of the CAD patients without BMS, DES, or CABG.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariable analysis of risk factors effecting mortality in CAD patients, 2005-2015\u003csup\u003ea\u003c/sup\u003e.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\n \u003cp\u003eCoronary intervention (Reference: BMS)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCABG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;39 418; deaths\u0026thinsp;=\u0026thinsp;12 974; LR\u0026thinsp;=\u0026thinsp;12 032.08; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003eCox model controlled for sex, age at CAD diagnosis / coronary intervention, cardiovascular and non-cardiac diseases, years since intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eDES and CABG showed similar survival advantages in 3-year mortality follow-up which based on a large number of CAD patients. Among the different operative procedures, BMS indicated worse results but worst survival outcomes we found for CAD patients who never underwent coronary intervention. The descriptive results also confirmed a more frequently application of stents compared to bypass surgery. Thus, we are able to replicate the findings of earlier studies but extended them to a longer follow-up period and used a larger sample size with higher representativity of the general population.\u003c/p\u003e \u003cp\u003eWhen interpreting the results of our study it is important to consider that the analysis included various types of CAD morphology. Earlier studies showed disparities in survival outcomes between DES and CABG for specific CAD profiles. With the adjustment for risk factors of death in multivariable analysis, the tendency of DES to be superior over CABG in Kaplan-Meier estimates ceased. The survival curves implied a higher postoperative mortality risk of open-surgical procedure in first year after intervention compared to catheter-based revascularization, but also showed the long-term benefit of CABG after 3 years of follow-up. Our study confirmed non-inferiority for DES as compared to CABG and thus indicated favorable results for aging populations with high burden of ischemic heart disease. However, the equality of survival outcomes for DES and CABG possibly emerged due to the healthier and younger CAD patients who received bypass surgery. On the other hand, it can be estimated that less complex CAD, i.e. one- and two vessel disease, was preferentially treated by DES regardless patients age. High mortality in patients who never received coronary intervention can be caused by a delayed first diagnosis of CAD, a general worse health profile or patient\u0026rsquo;s preferences to reject an operative procedure.\u003c/p\u003e \u003cp\u003eFurthermore, our study revealed less expected results. Patients with BMS showed worse survival outcomes as compared to DES or CABG. Nevertheless, BMS represents the most frequent procedure used between 2005 and 2012. According to the current state of medical research, the BMS can be seen as historical in clinical importance. Hence, there is seldom a compelling reason to prefer BMS to DES [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Drug-eluting stents were developed to improve the long-term efficacy and safety of patients receiving percutaneous coronary interventions and hitherto represents the gold standard in interventional CAD treatment [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the generally higher number of deaths in male CAD patients, the missing sex-gradient in mortality in our study supports earlier studies that point towards a more severe progression of disease in women due to a delayed first CAD diagnosis.\u003c/p\u003e \u003cp\u003eProspective clinical trials demonstrated clinical advantages regarding survival and/or subsequent cardiac events for either treatment method depending on specific CAD morphologies, e.g. isolated left main stenosis or three-vessel disease [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A large retrospective study by Head et al. (2018) analyzed differences in mortality following PCI or CABG in patients with multivessel-disease and left main stem stenosis. Similar to the mentioned prospective clinical trials this pooled analysis of individual patient data found a mortality benefit for CABG over PCI in patients with multivessel-disease whereas no benefit for CABG over PCI was seen in left main disease [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The strength and main clinical impact of the retrospective results presented here is that data were obtained from a large patient cohort without pre-specifying for certain coronary morphologies including even one- and two-vessel disease. In this way our data provided a unique validation of early and midterm survival following invasive CAD treatment on an observational basis in \u0026ldquo;a real-world scenario and matched the overall survival results following PCI or CABG performed within prospective clinical trials.\u003c/p\u003e"},{"header":"Strengths And Limitations","content":"\u003cp\u003eAn important advantage of this health claims analysis was the large sample size concerning the number of CAD patients and different coronary interventions, just as the range of diagnoses from all fields of medicine. Also, the cohort design offered a long observation period of twelve years to track patient\u0026rsquo;s health status and changes over time. We reduced false-positive diagnoses of CAD by using a validation strategy and assumed high validity of the diagnoses, which based on medical examinations of practicing physicians, and the interventions because health claims data aims to document medical treatments and their costs.\u003c/p\u003e \u003cp\u003eThe elimination of false-negative CAD diagnoses was possible due to the wash-out period in 2004 but came up again when patients received their second diagnosis of coronary artery disease after 2014. Another limitation concerned that our data based on all-cause mortality and was limited to medical or demographic risk factors of death. Also, the patient\u0026rsquo;s preferences have to be considered, who often favor a less invasive treatment strategy.\u003c/p\u003e \u003cp\u003eIn contrast to clinical trials, our official process-generated data source (\u0026lsquo;AOK\u0026rsquo;) was not affected by self-selected dropouts, reactivity (e.g. social desirability), any response biases and any cognitive biases (e.g. recall bias or overconfidence bias). To solve three general problems of observational studies: The mortality selection bias, the end-of-study-bias, and the immortal time bias, we opposed the biases by emulating a randomized target trial following pre-defined eligibility criteria [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur results strengthened the interdisciplinary approach in treating CAD patients by either percutaneous coronary intervention using DES or CABG are clearly demonstrated to represent complementary rather than competing treatment options. An early survival benefit of PCI using DES is supplemented by an advantage of CABG regarding the mid and long-term survival. Similar to the treatment of structural heart disease, institutional Heart Teams consisting of cardiac surgeons and cardiologists should evaluate CAD cases on a routine basis and allocate patients to the optimal treatment, thereby taking in account patient age, comorbidities and the specific morphology (i.e. single or multi-vessel disease, presence or absence of left main stenosis) of the underlying CAD. There is a need for future long-term observational analyses, such as the one presented here, but with a focus on specific coronary morphologies in order to compare their results of surgical versus interventional CAD treatments in large cohorts of patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to Christian G\u0026uuml;nster from the Scientific Research Institute of the AOK, WIdO, for providing the data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Federal Ministry of Education and Research, Germany, Grant number 03ZZ0923A.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eD.K. and G.D. designed the model and the computational framework. G.D. supervised the work. S.N. performed the calculations and designed the figures and tables. S.N. wrote the original draft. G.D., D.K., P.D., and H.I. reviewed and edited the manuscript with input from all authors. All authors discussed the results and contributed to the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe scientific research institute of the AOK (WIdO) has strict rules regarding data sharing because health claims data are a sensitive data source and have ethical restrictions imposed due to concerns regarding privacy. Anonymized data are available to all interested researchers upon request. Interested individuals or an institution who wish to request access to the health claims data of the AOK may contact the WIdO (webpage: http://www.wido.de/, mail: [email protected]).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980\u0026ndash;2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. 2016;388:1459\u0026ndash;544. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(16)31012-1\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(16)31012-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaas AH, Appelman YEA. Gender differences in coronary heart disease. Neth Heart J. 2010;18:598\u0026ndash;603.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeymer U, Zahn R, Hochadel M, Bonzel T, Weber M, Gottwik M, et al. Incications and complications of invasive diagnostic procedures and percutaneous coronary interventions in the year 2003. Z f\u0026uuml;r Kardiologie. 2005;94:392\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeinertz T, Hamm C, Schlensak C, Fleck E, Cremer J, Stiller B, et al. Deutscher Herzbericht 2016: 28. Bericht/Sektoren\u0026uuml;bergreifende Versorgungsanalyse zur Kardiologie, Herzchirurgie und Kinderherzmedizin in Deutschland: Deutsche Herzstiftung; 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBabapulle MN, Joseph L, B\u0026eacute;lisle P, Brophy JM, Eisenberg MJ. A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents. The Lancet. 2004;364:583\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVillareal RP, Lee V-V, Elayda MA, Wilson JM. Coronary artery bypass surgery versus coronary stenting: risk-adjusted survival rates in 5,619 patients. Tex Heart Inst J. 2002;29:3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStone GW, Kappetein AP, Sabik JF, Pocock SJ, Morice M-C, Puskas J, et al. Five-year outcomes after PCI or CABG for left main coronary disease. N Engl J Med. 2019;381:1820\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM\u0026auml;kikallio T, Holm NR, Lindsay M, Spence MS, Erglis A, Menown IBA, et al. Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial. The Lancet. 2016;388:2743\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGuire TG, van Kleef RC. Risk, Adjustment. Risk Sharing and Premium Regulation in Health Insurance Markets: Theory and Practice. London: Academic Press; 2018.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEmilsson L, Garc\u0026iacute;a-Alb\u0026eacute;niz X, Logan RW, Caniglia EC, Kalager M, Hern\u0026aacute;n MA. Examining bias in studies of statin treatment and survival in patients with cancer. JAMA Oncol. 2018;4:63\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHern\u0026aacute;n MA, Sauer BC, Hern\u0026aacute;ndez-D\u0026iacute;az S, Platt R, Shrier I. Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses. J Clin Epidemiol. 2016;79:70\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAriotti S, Adamo M, Costa F, Patialiakas A, Briguori C, Thury A, et al. Is bare-metal stent implantation still justifiable in high bleeding risk patients undergoing percutaneous coronary intervention? A pre-specified analysis from the ZEUS trial. JACC: Cardiovasc Interventions. 2016;9:426\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuranik AS, Dawson ER, Peppas NA. Recent advances in drug eluting stents. Int J Pharm. 2013;441:665\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThuijs DJ, Kappetein AP, Serruys PW, Mohr F-W, Morice M-C, Mack MJ, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial. The Lancet. 2019;394:1325\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHead SJ, Milojevic M, Daemen J, Ahn J-M, Boersma E, Christiansen EH, et al. Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. The Lancet. 2018;391:939\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e\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":true,"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":"coronary artery disease, stents, coronary artery bypass, health claims data, follow-up, mortality","lastPublishedDoi":"10.21203/rs.3.rs-1366225/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1366225/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eDue to demographic aging, the prevalence of coronary artery disease (CAD) is expected to increase in the future, resulting in a growing demand for stent and bypass interventions. This study aims to investigate the mortality risk of patients following conventional coronary artery bypass grafting (CABG) or endovascular procedure by the implantation of bare-metal stents (BMS) or drug-eluting stents (DES).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eBased on a random sample of 250,000 members of Germany’s largest health insurance ‘Allgemeine Ortskrankenkassen’ (AOK) from 2004 to 2015, incident CAD patients were analyzed by Cox Proportional-Hazard models. Risk adjustment was made for sex, age, other cardiac diseases, non-cardiovascular comorbidities and years since intervention. Due to later admission of DES and thus a shorter observation time, mortality was examined for 3 years since the intervention. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eBMS represented the most frequent procedure (48%). We found similar proportions of CABG (19%) and DES interventions (23%). After risk adjustment, the models showed a 21% (p=0.004) lower mortality risk of patients with DES and also a 21% (p=0.002) lower mortality risk of CABG patients compared to persons with BMS.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eBased on a large-scale dataset, our study demonstrated survival advantages of CABG and DES interventions over BMS, with no differences between the DES and CABG groups. The results help to assess the risks of coronary interventions. Aspects of quality of life, severity of postoperative physical limitations, duration of rehabilitation, patients’ preferences, and aspects of cost-effectiveness for hospitals and society should be further considered.\u003c/p\u003e","manuscriptTitle":"Stents versus Bypass Surgery – 3-Year Mortality Risk of Patients with Coronary Interventions Aged 50+ in Germany","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-06-23 18:05:40","doi":"10.21203/rs.3.rs-1366225/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2022-06-18T21:13:39+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-06-18T20:31:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-02-18T08:22:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cardiothoracic Surgery","date":"2022-02-16T10:13:44+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":"00e2527d-308d-4fb0-ba89-ecb809d06a6a","owner":[],"postedDate":"June 23rd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-09-24T19:41:32+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-23 18:05:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1366225","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1366225","identity":"rs-1366225","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}