August 27 2017 Rivaroxaban in stable peripheral or
August 27, 2017 Rivaroxaban in stable peripheral or carotid artery disease Sonia Anand, on behalf of the COMPASS Steering Committee and Investigators Independently conducted by PHRI, sponsored by Bayer AG 17 -07 -01
- Consu lting/Royalties/Owner/ Stockholder of a healthcare company (I receive speaking honoraria from Phrumaceutical comapnies)
COMPASS PAD rationale • PAD patients have widespread atherosclerosis and increased risk of CV & limb adverse outcomes • Vascular events are high despite effective interventions • Few therapies have clearly reduced both Major Adverse CV Events (MACE) and Major Adverse Limb Events (MALE) 17 -07 -01
Primary objectives To determine in PAD whether: • Rivaroxaban 2. 5 mg bid + aspirin 100 mg od, or • Rivaroxaban 5 mg bid reduce the risk of MACE and MALE as compared with aspirin 100 mg od 17 -07 -01
Eligibility: PAD • Peripheral artery revascularization • Limb or foot amputation for arterial vascular disease • Intermittent claudication plus: – Low ABI (<0. 90), or – Significant peripheral artery stenosis (≥ 50%) • Previous carotid revascularization, asymptomatic carotid artery stenosis ≥ 50% • CAD + low ABI (<0. 90) 17 -07 -01
Key Efficacy Outcomes • Primary Cardiovascular Outcome (MACE): - CV death, stroke, or MI • Major Adverse Limb Events (MALE): – Severe limb ischemia leading to an intervention (angioplasty, bypass surgery, amputation, thrombolysis) – Major Amputation above forefoot due to vascular cause 17 -07 -01
Primary Safety Outcome • Major Bleeding: Modified ISTH • Net Clinical Benefit: MACE, MALE, major amputation, fatal bleeding, or symptomatic bleeding into a critical organ 17 -07 -01
PAD Patients in COMPASS PAD Groups All Patients Number of patients 7, 470 Symptomatic PAD Limbs 4, 129 Carotid Disease 1, 919 CAD + Low ABI (<0. 90) only 1, 422 Mean Follow-up: 21 months 17 -07 -01
Baseline Characteristics Characteristic Age, years (mean) Current Smoker Former Smoker Diabetes Hypertension Prior CAD or Stroke Lipid Lowering ACE-I/ARB Riva + aspirin Rivaroxaban N=2, 492 N=2, 474 68 68 27% 28% 46% 47% 44% 79% 78% 69% 84% 69% 71% Aspirin N=2, 504 68 27% 46% 44% 81% 68% 83% 70%
Primary outcome & components R+A N=2, 492 Outcome N (%) 126 MACE (5. 1) 51 MI (2. 0) 25 Stroke (1. 0) 64 CV Death (2. 6) R N=2, 474 N (%) 149 (6. 0) 56 (2. 3) 43 (1. 7) 66 (2. 7) A N=2, 504 N (%) 174 (6. 9) 67 (2. 7) 47 (1. 9) 78 (3. 1) Riva + aspirin vs. aspirin HR P (95% CI) 0. 72 0. 005 (0. 57 -0. 90) 0. 76 (0. 53 -1. 09) 0. 54 (0. 33 -0. 87) 0. 82 (0. 59 -1. 14) Riva vs. aspirin HR (95% CI) 0. 86 (0. 69 -1. 08) 0. 84 (0. 59 -1. 20) 0. 93 (0. 61 -1. 40) 0. 86 (0. 62 -1. 19) P 0. 19 - August 11, 2017
Limb outcomes R+A R A Riva + aspirin vs. Riva vs. aspirin N=2, 492 N=2, 474 N=2, 504 aspirin Outcome N N N HR HR P P (%) (%) (95% CI) MALE 30 35 56 0. 54 0. 63 0. 005 0. 03 (1. 2) (1. 4) (2. 2) (0. 35 -0. 84) (0. 41 -0. 96) Major 5 8 17 0. 30 0. 46 0. 01 0. 07 amputation (0. 2) (0. 3) (0. 7) (0. 11 -0. 80) (0. 20 -1. 08) Aug 11, 2017
Key Composite Outcome MACE, MALE or Major amputation R+A N=2, 492 N (%) 157 (6. 3) R A N=2, 474 N=2, 504 N N (%) 188 (7. 6) 225 (9. 0) Riva + aspirin vs. aspirin HR P (95% CI) HR (95% CI) P 0. 69 0. 0003 (0. 56 -0. 85) 0. 84 (0. 69 -1. 02) 0. 08 Riva vs. aspirin August 14, 2017
0. 15 MACE or MALE or Major Amputation Aspirin Cumulative Hazard Rate 0. 05 0. 10 Rivaroxaban + Aspirin vs. Aspirin HR: 0. 69 (0. 56 -0. 85) P=0. 0003 0. 0 0 1 2492 2474 2504 2069 2023 2034 No. at Risk Riva + ASA Riva ASA HR: 0. 84 (0. 69 -1. 02) P=0. 08 Rivaroxaban vs. Aspirin 2 Year 893 864 911 3 124 147 113
Major bleeding Outcome Major Bleeding Fatal Non-Fatal ICH R+A N=2, 492 N (%) 77 (3. 1) 4 (0. 2) R N=2, 474 N (%) 79 (3. 2) 5 (0. 2) 3 (0. 1) A N=2, 504 N (%) 48 (1. 9) 3 (0. 1) 8 (0. 3) 13 (0. 5) 18 (0. 7) 8 (0. 3) Non-fatal other critical organ* * symptomatic Riva + aspirin vs. aspirin HR P (95% CI) 1. 61 0. 009 (1. 12 -2. 31) Riva vs. aspirin HR (95% CI) 1. 68 (1. 17 -2. 40) P 0. 004 - - - - 2. 15 (0. 94 -4. 96) 0. 06 1. 55 0. 33 (0. 64 -3. 74)
Net clinical benefit in PAD Outcome Net Clinical Benefit R+A R A N=2, 492 N=2, 474 N=2, 504 N (%) 169 (6. 8) 207 (8. 4) 234 (9. 3) Riva + aspirin vs. aspirin HR P (95% CI) 0. 72 0. 0008 (0. 59 -0. 87) Riva vs. aspirin HR (95% CI) 0. 89 (0. 74 -1. 07) P 0. 23 August 14, 2017
MACE, MALE or Major Amputation Overall COMPASS Overall PAD Symptomatic PAD Lower Extremeties Carotid Artery Disease 0 0. 5 Riva 2. 5 + ASA better 1. 0 1. 5 ASA only better
Conclusions Rivaroxaban 2. 5 mg BID plus aspirin is: - Significantly superior to aspirin alone in reducing MACE or MALE or major amputation (31% RRR) - Increased major bleeding, but no significant increase in fatal or critical organ bleeding 17 -07 -01
COMPASS PAD paper forthcoming in The Lancet Acknowledgements 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 thank all the investigators and study coordinators for their efforts We thank all participants for their selfless dedication
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