Rivaroxaban Plus Aspirin in Patients With and Without Heart Failure and Chronic Coronary or Peripheral Artery Disease The COMPASS Trial Kelley Branch MD MSc on behalf of the COMPASS Steering Committee and Investigators ID: 764417
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Rivaroxaban Plus Aspirin in Patients With and Without Heart Failure and Chronic Coronary or Peripheral Artery Disease: The COMPASS Trial Kelley Branch, MD, MSc, on behalf of the COMPASS Steering Committee and Investigators 1
BackgroundHeart failure (HF) affects over 26 million people worldwide and the incidence is expected to increase dramatically over the next decade HF with atherosclerotic coronary artery disease (CAD) and/or peripheral artery disease (PAD) leads to increased cardiovascular events compared to those without CAD or PAD2Ambrosy AP, et al. J Am Coll Cardiol 2014;63:1123-33. Shah KS, et al. J Am Coll Cardiol 2017;70:2476-2486. Jones WS , et al. Am J Cardiol;2011;108:380-384.
COMPASS DesignC ardiovascular Outcomes for People Using Anticoagulation Strategies Median Follow Up :23 months (1.9 years) Rivaroxaban 5 mg bid R Rivaroxaban 2.5 mg bid + aspirin 100 mg daily Aspirin 100 mg daily Run-in (aspirin) 27,325 patients with stable CAD or PAD 1,323 with a primary outcome event Randomized, placebo controlled, double blinded trial Ongoing arm testing proton pump inhibitor pantoprazole versus placebo (PPI arm) Eikelboom JW, et al. NEJM 2017; 377:1319-1330. 3
COMPASS Main Trial Outcomes Eikelboom JW, et al. NEJM 2017;377:1319-1330. Riva+ASA vs ASA:↓MACE 24%↑Net benefit 20%↓ Mortality 18%Primary Outcome: MACE (CV death, stroke or MI)Median 23 month follow upNo benefit for Riva alone ASA = aspirin; CV = cardiovascular; MACE = major adverse cardiovascular events; MI = myocardial infarction; Riva = rivaroxaban. Cumulative Hazard Time (years) ASA Riva+ASA Riva 4
COMPASS HF Substudy Outcomes Purpose: To explore the effects of combination rivaroxaban + aspirin compared with aspirin alone in chronic CAD and PAD patients with or without HFPrimary OutcomeMACE: Cardiovascular death, stroke or myocardial infarction Safety OutcomeISTH major bleeding (modified)Net Clinical BenefitPrimary MACE plus severe bleeding (fatal or critical organ bleeding)5
COMPASS HF Methods COMPASS exclusion criteria included severe heart failure with known left ventricular ejection fraction (LVEF) <30% or New York Heart Association (NYHA) class III or IV symptomsHF status was site reported (history or current) at baselineLVEF was recorded for trial participants, if available. Primary and safety outcomes compared by HF status Cox proportional hazard ratio calculated for each primary outcomeLog rank tests for interaction for HF groups were stratified by PPI armBosch J, et al. Can J Cardiol. 2017 Aug;33(8):1027-1035. 6
Baseline Characteristics Overall(N=27395)No HF(N=21493) HF (N=5902) P value Age ( yr ) 68.2±7.9 69.0±7.5 65.5±9.0 <0.0001 Female sex 6020 (22.0 ) 4653 (21.6 ) 1367 ( 23.2 ) 0.01Current smoker5867 (21.4)4114 (19.1)1753 (29.7) <0.0001 Hypertension 20632 (75.3) 15632 (72.7)5000 (84.7)<0.0001Diabetes 10341 (37.7) 7915 (36.8)2426 (41.1)<0.0001 Previous MI 17028 (62.2) 12497 ( 58.1 ) 4531 (76.8 ) <0.0001 White race 17027 (62.2 ) 13354 (62.1 ) 3673 (62.2 ) 0.89 PAD 7470 ( 27.3 ) 6079 ( 28.3 ) 1391 (23.6 ) <0.0001NYHA Class I/II/III--36%/64%/0.1%-eGFR <60 ml/min6276 (23%)4760 (22%)1516 (26%)<0.0001ACE inhibitor or ARB19518 (71.2)14866 (69.2)4652 (78.8)<0.0001Calcium-channel blocker7269 (26.5)5854 (27.2)1415 (24.0)<0.0001Diuretic8139 (29.7)5427 (25.3)2712 (46.0)<0.0001Beta blocker19184 (70.0)14382 (66.9)4802 (81.4)<0.0001Lipid-lowering agent24601 (89.8)19203 (89.3)5398 (91.5)<0.0001NSAID1470 (5.4)1193 (5.6)277 (4.7)0.01 7
Primary MACE Outcome by HF Status( CV death, stroke, MI)Riva + ASA N=9,152 ASA N=9,126 Rivaroxaban + aspirin vs. aspirin n/N (%) n/N (%) HR (95% CI) P No HF 271/7189 (3.8%) 339/7147 (4.7%) 0.79 (0.68-0.93) 0.28 HF 108/1963 (5.5%) 157/1979 (7.9%) 0.68 (0.53-0.86) P = p value for interaction by log-rank test by HF category 8
Primary MACE Outcome by HF Status HF, ASANo HF, ASAHF, Riva+ASANo HF, Riva+ASA HR 0.68(95% CI 0.53-0.86) ARR 2.4%NNT 42 HR 0.79 (95% CI 0.68-0.93) ARR 0.9% NNT 111 P=0.28 for interaction Cumulative Hazard Time (months) 9
Major (modified ISTH) bleedingP = p value for interaction by log-rank test by HF category 10Riva + ASAN=9,152 ASA N=9,126 Rivaroxaban + Aspirin vs. Aspirin n/N (%) n/N (%) HR (95% CI) P No HF 239/7189 (3.3) 134/7147 (1.9) 1.79 (1.45-2.21 ) 0.26 HF 49/1963 (2.5) 36/1979 (1.8) 1.36 (0.88-2.09 )
Net Clinical Benefit( Primary outcome + Severe bleeding events)Riva + ASA N=9,152 ASA N=9,126 Rivaroxaban + aspirin vs. aspirin n/N (%) n/N (%) HR (95% CI) P No HF 315/7189 (4.4)369/7147 (5.2 ) 0.85 (0.73-0.99 ) 0.15 HF 116/1963 (5.9 ) 165/1979 (8.3 ) 0.69 (0.55-0.88 ) P = p value for interaction by log-rank test by HF category 11
Net Clinical Benefit: Hazard Ratios( Primary outcome + Severe bleeding events) 0.85 (0.73-0.99) 0.69 (0.55-0.88) 0.76 ( 0.66-0.86) No HF HF Overall P=0.15 Net clinical benefit of patients with HF and no HF are consistent with overall trial Higher absolute risk reduction for patients with HF 12
LimitationsHF status was not explicitly defined or adjudicated at baselineRestricted to mild to moderate HF at baseline Baseline LVEF was incompletely collected (55% of patients)Cannot define HFpEF and HFrEFPlanned analysis after additional LVEF ascertainment13
COMPASS HF Substudy: Conclusions Patients with chronic CAD and PAD with HF have higher event rates than those without HFRivaroxaban + aspirin had consistent effects on primary MACE outcome and net clinical benefit in those with HF and without HFAbsolute risk benefits are greatest in those with HFPrimary Outcome: HF - absolute risk reduction (ARR) 2.4% (NNT 42) No HF – ARR 0.9% (NNT 111)Net clinical benefit: HF – ARR 2.4% (NNT 42) No HF – ARR 0.8% (NNT 125)Efficacy of rivaroxaban 2.5 mg bid + aspirin in HFrEF with CAD will be reported with recently completed COMMANDER HF trial14
Acknowledgments Steering Committee: S. Yusuf (Chair), K. Fox (Co-Chair), S. Connolly (Co-PI), JW. Eikelboom (Co-PI), J. Bosch (Study Director), V. Aboyans, M. Alings, S. Anand, A. Avezum, D. Bhatt, K. Branch, P. Commerford, N. Cook-Bruns, G. Dagenais, A. Dans, R. Diaz, G. Ertl, C. Felix, , T. Guzik, J. Ha, R. Hart, M. Hori, A. Kakkar, K. Keltai, M. Keltai, J. Kim, A. Lamy, F. Lanas, B. Lewis, Y. Liang, L. Liu, E. Lonn, P. Lopez-Jaramillo, A. Maggioni, K. Metsarinne, P. Moayyedi, M. O'Donnell, A. Parkhomenko, L. Piegas, N. Pogosova, J. Probstfield, L. Ryden, M. Sharma, P.G. Steg, S. Stoerk, A. Tonkin, C. Torp-Pedersen, J. Varigos, P. Verhamme, D. Vinereanu, P. Widimsky , K. Yusoff, J. Zhu We sincerely thank all investigators, study coordinators and participants 15