Author + information
- Received August 13, 2018
- Revision received October 3, 2018
- Accepted October 8, 2018
- Published online January 14, 2019.
- Andre Lamy, MDa,b,c,d,∗ (, )@McMasterU,
- John Eikelboom, MBBSa,e,
- Tej Sheth, MDa,e,
- Stuart Connolly, MDa,e,
- Jackie Bosch, PhDa,
- Keith A.A. Fox, MBChBf,
- Jun Zhu, MDg,
- Eva Lonn, MDa,d,e,
- Gilles Dagenais, MDh,
- Petr Widimsky, MDi,
- Kelly R.H. Branch, MDj,
- Deepak L. Bhatt, MDk,
- Zhe Zheng, MDg,
- Zbynek Straka, MDi,†,
- Francois Dagenais, MDl,
- Ye Kong, MDm,
- Tamara Marsden, MSa,
- Shun Fu Lee, PhDa,
- Ingrid Copland, CCRAa and
- Salim Yusuf, DPhila,d,e
- aPopulation Health Research Institute, McMaster University, Hamilton, Ontario, Canada
- bCADENCE Research Group, Hamilton Health Sciences, Hamilton, Ontario, Canada
- cDepartment of Surgery, McMaster University, Hamilton, Ontario, Canada
- dDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
- eDepartment of Medicine, McMaster University, Hamilton, Ontario, Canada
- fCentre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
- gFuWai Hospital, Beijing, China
- hInstitut Universitaire de Cardiologie et de Pnemologie de Québec, Quebec City, Quebec, Canada
- iCardiocenter, University Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic
- jUniversity of Washington Medical Center, Seattle, Washington
- kBrigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts
- lQuebec Heart and Lung University Institute, Laval University, Quebec City, Quebec, Canada
- mShanghai Chest Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, China
- ↵∗Address for correspondence:
Dr. Andre Lamy, DBCVSRI C1-112, 237 Barton Street, East Hamilton, Ontario L8L 2X2, Canada.
Background Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE.
Objectives This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery.
Methods The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery.
Results The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization.
Conclusions The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424)
Coronary artery bypass grafting (CABG) reduces mortality in patients with extensive coronary artery disease (CAD) (1). However, 1 of the major limitations of CABG is early graft failure, mainly caused by thrombotic occlusion (2–4), which increases the risk of myocardial infarction (MI) and death. Acetylsalicylic acid (aspirin) prevents early graft failure, but despite its routine use, as many as 30% of patients have at least 1 occluded graft 1 year after CABG surgery (3,4). In the Post Coronary Artery Bypass Graft Trial, fixed-dose warfarin did not reduce graft failure (5), but it reduced nonfatal MI or death during a longer follow-up (7.5 years) (6).
The COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial demonstrated that rivaroxaban 2.5 mg twice daily in combination with aspirin 100 mg once daily was more effective than aspirin 100 mg once daily for the prevention of cardiovascular (CV) death, stroke, or MI in patients with stable CAD or peripheral artery disease (PAD) (7), whereas rivaroxaban alone was not beneficial. The COMPASS CABG study was a pre-planned, specifically designed substudy to evaluate whether rivaroxaban with or without aspirin would be more effective than aspirin for preventing bypass graft failure at 1 year in patients with CAD who had recent CABG surgery.
COMPASS was a double-blind, randomized trial with a 3 × 2 partial factorial design, involving 27,395 patients with stable CAD or PAD from 602 centers in 33 countries (8). The trial evaluated rivaroxaban 2.5 mg twice daily in combination with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily with matched placebo once daily, compared with aspirin 100 mg once daily with matched placebo twice daily for the prevention of the composite of CV death, stroke, or MI among those patients with a history of stable CAD or PAD. In the second partial factorial randomization, patients not already taking a proton pump inhibitor were also randomized to either pantoprazole 40 mg once daily or matched placebo once daily. The antithrombotic comparisons were stopped early for efficacy following a recommendation by the independent Data and Safety Monitoring Board. The combination of rivaroxaban and aspirin compared with aspirin alone reduced the primary outcome by 24% (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.66 to 0.86; p < 0.0001), whereas rivaroxaban 5 mg twice daily alone did not significantly reduce major adverse CV events (MACE) (7). The early termination of the COMPASS trial occurred at a mean follow-up of 23 months, and the CABG substudy also ended at this time.
Eligibility and randomization
Patients were eligible for the overall study if they had CAD or PAD, met the inclusion criteria and did not meet the exclusion criteria, and provided written informed consent (7). Patients who underwent CABG surgery within 4 to 14 days were eligible for inclusion in the specifically designed CABG substudy if they had at least 2 grafts implanted and an estimated glomerular filtration rate of at least 30. Patients undergoing concomitant procedures could be enrolled as long as they did not undergo a procedure that required anticoagulation (e.g., mechanical valve replacement). Patients with atrial fibrillation were not eligible if they required anticoagulation. There was no run-in phase for the patients enrolled in the CABG substudy.
Eligible participants were randomized 4 to 14 days after CABG surgery in a 1:1:1 ratio to receive rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg once daily, stratified by center. The first dose of the study medication was given at the time of randomization. The patients were randomized also to pantoprazole 40 mg daily or matched placebo if they were not taking a proton pump inhibitor. After randomization, participants were seen at 1 and 6 months and subsequently at 6-month intervals. A final evaluation was conducted by telephone 30 days after completion of rivaroxaban and aspirin treatment.
The primary outcome was the proportion of coronary bypass grafts that had failed with complete occlusion of the graft (vessel-level analysis) (8). The secondary outcome was the proportion of patients with at least 1 failed graft (patient-level analysis). Graft failure was assessed with a computed tomography angiogram (CTA) at 1 year after surgery, or with conventional coronary angiography if this had been performed for a clinical indication. Two experienced readers blinded to all patients’ data evaluated the CTAs in a core laboratory. Grafts were evaluated for image quality (evaluable without artifacts, with artifacts, or nonevaluable). Among all evaluable grafts, graft patency was determined with a modified FitzGibbon ABO nomenclature (9) and categorized as follows: 1) normal lumen (<50% stenosis); 2) moderate stenosis ≥50% to 75% stenosis; 3) severe stenosis (>75% to 99% stenosis); 4) string sign (graft diameter <2 mm); or 5) occluded graft. When a reduction in lumen caliber was observed, the location was determined to be: 1) proximal anastomosis; 2) body of graft; 3) distal anastomosis; or 4) entire graft.
The clinical efficacy outcomes were the COMPASS primary composite of CV death, MI, or stroke (7). The main safety outcome was a modification of the International Society on Thrombosis and Hemostasis criteria for major bleeding (10), which included fatal bleeding, symptomatic bleeding in a critical organ, bleeding into a surgical site requiring reoperation, and bleeding leading to hospitalization (including presentation to an acute care facility without overnight stay).
Baseline characteristic are presented for all COMPASS patients, COMPASS patients randomized 4 to 14 days after CABG surgery, and those randomized 4 to 14 days after CABG surgery who underwent CTAs. Baseline characteristics are compared among the 3 treatment groups using analysis of variance for continuous variables and a chi-square test for categorical variables.
All clinical events that occurred between randomization and the date of end of observation (February 6, 2017) were analyzed on the basis of the intention-to-treat principle. Comparisons of outcomes were performed between each of the rivaroxaban-based groups and the common aspirin control group. “The primary outcome of proportion of grafts occluded (bypass graft-level) was analyzed using mixed logistic regression (i.e., GLIMMIX procedure in SAS; SAS Institute, Cary, North Carolina) with random effects to account for multiple grafts within individuals.” The proportion of patients with 1 or more grafts occluded was evaluated using logistic regression models. The odds ratio (OR) and the corresponding 95% confidence intervals (CIs) are reported. Both patient-level and bypass graft-level analyses were performed. Cox regression was used to assess the clinical and safety outcomes, and results are reported as hazard ratios (HRs) with 95% CI.
Of the 27,395 individuals enrolled in COMPASS, 1,448 patients were randomized 4 to 14 days after CABG surgery. Baseline characteristics of the COMPASS participants, CABG-treated patients who were randomized, and those who underwent a CTA are shown in Table 1. Compared with non-CABG participants, CABG-treated patients were younger, had less prior MI, PAD, and renal insufficiency but more diabetes, and were taking more diuretic agents and beta-blockers. Baseline characteristics of the 3 randomized groups were similar (Table 2).
Surgical characteristics per treatment groups are shown in Table 3. Left main coronary artery stenosis was present in 352 patients (24.3%), triple-vessel disease in 1,131 patients (78.1%), double-vessel disease in 249 (17.2%), and single-vessel disease in 44 patients (3.0%). All but 8 patients (0.6%) underwent median sternotomy. The number of grafts per participant was similar in the 3 randomized groups (mean of 3.1 grafts per patient). Forty patients (2.8%) received a concomitant bioprosthetic aortic valve replacement (n = 34) or mitral valve repair (n = 5), or both (n = 1). A CTA was performed at 12 months after CABG surgery in 1,139 (78.3% of randomized patients) of patients, and conventional coronary angiography was performed in 9 patients (Figure 1). Few grafts (n = 14) patency could not be evaluated for technical reasons, but overall 3,562 grafts were evaluable. The mean follow-up time between randomization and CTA was 1.13 ± 0.30 years.
Primary and other pre-specified outcomes
Of the 3,562 grafts evaluated, 296 (8.3%) were occluded. The rate of graft occlusion was 9.1% in the rivaroxaban plus aspirin group, compared with 7.8% in the rivaroxaban-alone group and compared with 8.0% in the aspirin-alone group (Table 4). For the comparison of rivaroxaban plus aspirin versus aspirin alone, the OR for graft occlusion was 1.13 (95% CI: 0.82 to 1.57; p = 0.45). For the comparison of rivaroxaban alone with aspirin alone, the OR was 0.95 (95% CI: 0.67 to 1.33; p = 0.75). The secondary outcome of patient-level graft occlusion showed 86 patients (21.7%) having 1 or more grafts occluded in the rivaroxaban plus aspirin group, compared with 68 patients (17.8%) in the rivaroxaban-alone group and compared with 75 patients (20.7%) in the aspirin-alone group (Table 5). For the comparison of rivaroxaban plus aspirin versus aspirin alone, the OR was 1.06 (95% CI: 0.75 to 1.50; p = 0.74). For the comparison of rivaroxaban alone with aspirin alone, the OR was 0.83 (95% CI: 0.58 to 1.20; p = 0.32).
The primary clinical outcome of the main COMPASS trial (CV death, MI, and stroke) occurred in this CABG substudy in 12 (2.4%) patients in the rivaroxaban plus aspirin group, compared with 16 (3.3%) in the rivaroxaban alone and 16 (3.5%) in the aspirin-alone group (Table 6). For the comparison of rivaroxaban plus aspirin versus aspirin alone, the HR was 0.69 (95% CI: 0.33 to 1.47; p = 0.34). For the comparison of rivaroxaban alone versus aspirin alone, the HR was 0.99 (95% CI: 0.50 to 1.99; p = 0.98). Results for percutaneous coronary intervention, heart failure, venous thromboembolism, and hospitalization for CV causes are shown in Table 6.
Major bleeding in the first 30 days after CABG occurred in 2 (0.4%) participants who were randomized to receive rivaroxaban plus aspirin, 1 (0.2%) of those who received rivaroxaban alone, and 5 (1.1%) of those who received aspirin alone (Table 7). For the comparison of rivaroxaban plus aspirin versus aspirin alone, the HR was 0.37 (95% CI: 0.07 to 1.88; p = 0.21). For the comparison of rivaroxaban alone versus aspirin alone, the HR was 0.19 (95% CI: 0.02 to 1.61; p = 0.09). There was no fatal bleeding, reoperation for bleeding, or cardiac tamponade.
Major bleeding after the first 30 days occurred in 12 (2.4%) participants who were randomized to receive rivaroxaban plus aspirin, 19 (3.9%) of those who received rivaroxaban alone, and 8 (1.7%) among those who received aspirin alone. For the comparison of rivaroxaban plus aspirin versus aspirin alone, the HR was 1.41 (95% CI: 0.58 to 3.45; p = 0.45). For the comparison of rivaroxaban alone versus aspirin alone, the HR was 2.43 (95% CI: 1.06 to 5.54; p = 0.03).
We observed no difference in the proportion of occluded coronary bypass grafts or in the proportion of patients with at least 1 occluded graft between those randomized to rivaroxaban plus aspirin or rivaroxaban alone and those randomized to aspirin alone. The number of clinical events in the study was modest, but the overall results were consistent with the main COMPASS study findings in suggesting that rivaroxaban 2.5 mg twice daily plus aspirin compared with aspirin alone will also reduce MACE (Central Illustration). Rivaroxaban alone compared with aspirin alone did not produce any benefit, which is also consistent with the main COMPASS study results.
In the first 30 days after randomization post–CABG surgery, the rate of major bleeding was low, and there was no fatal bleeding or tamponade despite starting anticoagulation as early as 4 days after surgery and without a run-in period. This suggests that it is safe to add rivaroxaban 2.5 mg twice daily to aspirin soon after surgery.
Our results are also consistent with those of the Post Coronary Artery Bypass Graft Trial, which did not show a benefit of fixed low-dose warfarin for prevention of graft failure (5) in 1,351 patients who had CABG surgery 1 to 11 years before randomization. However, after 7.5 years of follow-up, there was a reduction in nonfatal MI or death (6).
It is possible that the lack of difference in graft patency among the 3 treatment arms is explained by the low power, because the COMPASS trial was stopped early, and by the fact that not all randomized patients underwent a CTA. Alternatively, it is possible that factor Xa inhibitors do not prevent graft failure because they are relatively ineffective in preventing thrombosis induced by exposure of blood to artificial surfaces such as a venous conduit implanted in an arterial vascular bed (11,12). Most patients received at least 1 arterial graft, and these are less likely to occlude than venous grafts, thereby further limiting study power. The rate of occlusion of the left internal mammary graft was 4.5% (49 of 1,088) compared with a venous graft occlusion rate of 9.6% (221 of 2,292). The rate of venous graft occlusion at 1 year was also lower in COMPASS (9.6%) than in older trials such as ROOBY (Randomized On/Off Bypass) (19.7%) (3), PREVENT-IV (Prevention of Autogenous Vein Graft Failure in Coronary Artery Bypass Procedures) (26.4%) (4), or the more recent DACAB (Compare the Efficacy of Different Antiplatelet Strategy After Coronary Artery Bypass Graft Surgery) trial (17.3%) (13). Similarly, the rate of patients with at least 1 graft occluded was much lower in COMPASS (229 of 1,139; 20.1%) than in ROOBY (32.6%) (3), PREVENT-IV (41.8%) (4), and DACAB (27.5%) (13).
The DACAB trial (13) reported that ticagrelor with aspirin significantly increases graft patency compared with aspirin alone in patients undergoing off-pump CABG (p < 0.001) but not in those undergoing on-pump CABG (p = 0.20). In COMPASS, the combination of rivaroxaban and aspirin compared with aspirin alone did not improve graft patency irrespective of surgical approach. Conversely, rivaroxaban alone compared with aspirin alone improved graft patency in patients undergoing off-pump CABG (p = 0.01) but not in those undergoing on-pump CABG (p = 0.74). Other trials have demonstrated that off-pump CABG is associated with lower rates of graft patency (3,14). There are a few possible explanations. First, the use of cardiopulmonary bypass in on-pump CABG results in platelet dysfunction (15), likely related to cellular trauma and coagulation factors consumption. Off-pump CABG surgery does not use cardiopulmonary bypass and is therefore likely associated with a prothrombotic state compared with on-pump CABG surgery. This interpretation is supported by the observation that off-pump CABG surgery compared with on-pump CABG surgery is associated with lower rates of bleeding (16). Second, off-pump CABG is technically more challenging and is associated with lower graft patency rates, which may explain the lack of benefit over on-pump surgery during long-term follow-up (17,18). Although we have to keep in mind that no rivaroxaban regimen had significant clinical benefits in this study, these data suggest that further evaluation of intensified antithrombotic therapy is warranted in patients undergoing off-pump CABG surgery (19).
First, we randomized fewer patients than planned, mostly because of the reluctance of surgeons and cardiologists to use rivaroxaban alone without aspirin after urgent CABG surgery in patients admitted for an acute coronary syndrome or MI. Patients with a recent acute coronary syndrome or MI who are at highest risk of early graft failure represented only 22% of the patients recruited. Various guidelines for patients with acute coronary syndrome and post-CABG patients also recommend the use of dual-antiplatelet therapy, which was an exclusion criterion for COMPASS. This reluctance is based on various guidelines for patients with CAD that recommend use of dual-antiplatelet therapy in these patients. Second, about 10% of patients did not undergo CTA at 1 year after CABG surgery for a medical reason, and another 12% simply refused the angiogram for personal reasons. This substantially limited power to detect a benefit of rivaroxaban-based therapy.
The combination of rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily or rivaroxaban 5 mg twice daily alone compared with aspirin 100 mg daily alone did not reduce graft failure in patients with recent CABG surgery. In the first 30 days after CABG surgery, there was no fatal bleeding or tamponade despite starting anticoagulation as early as 4 days after surgery and without a run-in period. The combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE as observed in the larger COMPASS trial. Therefore, it is reasonable and safe to use the combination of rivaroxaban 2.5 mg twice daily plus aspirin in patients who undergo CABG surgery.
COMPETENCY IN MEDICAL KNOWLEDGE: Compared with aspirin or rivaroxaban alone, the combination of rivaroxaban and aspirin did not prevent early failure of CABGs but reduced MACE, consistent with outcomes in the overall COMPASS trial.
TRANSLATIONAL OUTLOOK: Future trials should examine other antithrombotic strategies to prevent progression of atherosclerosis, increase long-term bypass graft patency, and improve the prognosis of patients undergoing CABG surgery.
↵† Dr. Straka is deceased.
This substudy was part of the COMPASS study, which was supported by grants from Bayer. Dr. Eikelboom has received grants and personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Daiichi-Sankyo, Janssen, AstraZeneca, Eli Lilly, GlaxoSmithKline, and Sanofi. Dr. Connolly has received grants from Bayer; and has received personal fees from Bristol-Myers Squibb, Pfizer, Portola, Boehringer Ingelheim, Servier, Daiichi-Sankyo, Medtronic, and Abbott. Dr. Bosch has received grants from and is on the advisory board of Bayer. Dr. Fox has received grants and personal fees from Bayer, Janssen, and AstraZeneca; has received personal fees from Sanofi and Regeneron; and has served as a consultant to Vereon. Dr. Zhu has received personal fees from Bayer, Boehringer Ingelheim, and Sanofi. Dr. Lonn has received personal fees from Bayer, Amgen, Sanofi, Novartis, and Servier; is on the advisory board of Bayer, Amgen, and Sanofi; and has received lecture honoraria from Bayer, Amgen, Sanofi, and Novartis. Dr. Widimsky is on the advisory board of Bayer. Dr. Branch has received grants from Bayer and Astellas; is on the advisory board of Janssen and Bayer; and has received other fees from Janssen. Dr. Bhatt is on the advisory boards of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; is on the board of directors of Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; is Chair of the American Heart Association Quality Oversight Committee; is on the data monitoring committees of the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and Population Health Research Institute; has received honoraria from the American College of Cardiology (as Senior Associate Editor of Clinical Trials and News, ACC.org; and as vice-chair of the ACC Accreditation Committee), Baim Institute for Clinical Research ([formerly Harvard Clinical Research Institute] for membership on the RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (as Editor-in-Chief of Harvard Heart Letter), Duke Clinical Research Institute (for membership on clinical trial steering committees), HMP Global (as Editor-in-Chief of the Journal of Invasive Cardiology), Journal of the American College of Cardiology (as Guest Editor and Associate Editor), Population Health Research Institute (for membership on the COMPASS operations committee, the publications committee, and the steering committee; and as USA national co-leader, funded by Bayer), Slack Publications (as Chief Medical Editor of Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (as Secretary/Treasurer), and WebMD (for membership on the CME steering committees); is the Deputy Editor of Clinical Cardiology; is the Chair of the NCDR-ACTION Registry Steering Committee and the VA CART Research and Publications Committee; has received research funding from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (as editor of Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is Site Co-Investigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; is a Trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo, Merck, Novo Nordisk, PLx Pharma, and Takeda. Dr. Yusuf has received grants and personal fees from Bayer, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, and Cadila; and has received consultant and speaker fees and travel expenses from Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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- Abbreviations and Acronyms
- coronary artery bypass grafting
- coronary artery disease
- confidence interval
- computed tomography angiogram
- hazard ratio
- major adverse cardiovascular events
- myocardial infarction
- odds ratio
- peripheral artery disease
- Received August 13, 2018.
- Revision received October 3, 2018.
- Accepted October 8, 2018.
- 2019 American College of Cardiology Foundation
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