1. 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

2. Background
Heart 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 PAD
Ambrosy AP, et al. J Am Coll Cardiol 2014;63: Shah KS, et al. J Am Coll Cardiol 2017;70: Jones WS, et al. Am J Cardiol;2011;108:

3. 27,325 patients with stable CAD or PAD
COMPASS Design Cardiovascular Outcomes for People Using Anticoagulation Strategies
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)
Rivaroxaban 5 mg bid R
Rivaroxaban 2.5 mg bid
+ aspirin 100 mg daily
Aspirin 100 mg daily
Run-in
(aspirin)
Median
Follow Up:
23 months (1.9 years)
Eikelboom JW, et al. NEJM 2017;377:

4. COMPASS Main Trial Outcomes
Primary Outcome: MACE (CV death, stroke or MI)
Median 23 month follow up
Riva+ASA vs ASA:
↓MACE 24%
↑Net benefit 20%
↓ Mortality 18%
ASA
Riva
Riva+ASA
Cumulative Hazard
No benefit for Riva alone
ASA = aspirin; CV = cardiovascular; MACE = major adverse cardiovascular events; MI = myocardial infarction; Riva = rivaroxaban.
Time (years)
Eikelboom JW, et al. NEJM 2017;377:

5. 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 HF
Primary Outcome
MACE: Cardiovascular death, stroke or myocardial infarction
Safety Outcome
ISTH major bleeding (modified)
Net Clinical Benefit
Primary MACE plus severe bleeding (fatal or critical organ bleeding)

6. 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 symptoms
HF status was site reported (history or current) at baseline
LVEF was recorded for trial participants, if available.
Primary and safety outcomes compared by HF status
Cox proportional hazard ratio calculated for each primary outcome
Log rank tests for interaction for HF groups were stratified by PPI arm
Bosch J, et al. Can J Cardiol Aug;33(8):

7. 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)
0.01
Current smoker
5867 (21.4)
4114 (19.1)
1753 (29.7)
Hypertension
20632 (75.3)
15632 (72.7)
5000 (84.7)
Diabetes
10341 (37.7)
7915 (36.8)
2426 (41.1)
Previous MI
17028 (62.2)
12497 (58.1)
4531 (76.8)
White race
17027 (62.2)
13354 (62.1)
3673 (62.2)
0.89
PAD
7470 (27.3)
6079 (28.3)
1391 (23.6)
NYHA Class I/II/III -
36%/64%/0.1%
eGFR <60 ml/min
6276 (23%)
4760 (22%)
1516 (26%)
ACE inhibitor or ARB
19518 (71.2)
14866 (69.2)
4652 (78.8)
Calcium-channel blocker
7269 (26.5)
5854 (27.2)
1415 (24.0)
Diuretic
8139 (29.7)
5427 (25.3)
2712 (46.0)
Beta blocker
19184 (70.0)
14382 (66.9)
4802 (81.4)
Lipid-lowering agent
24601 (89.8)
19203 (89.3)
5398 (91.5)
NSAID
1470 (5.4)
1193 (5.6)
277 (4.7)

8. 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 (%)
HR (95% CI) P
No HF
271/7189 (3.8%)
339/7147 (4.7%)
0.79 ( )
0.28 HF
108/1963 (5.5%)
157/1979 (7.9%)
0.68 ( )
P = p value for interaction by log-rank test by HF category

9. Primary MACE Outcome by HF Status
P=0.28 for interaction
HF, ASA
HR 0.68
(95% CI )
ARR 2.4%
NNT 42
No HF, ASA
Cumulative Hazard
HF, Riva+ASA
HR 0.79
(95% CI )
ARR 0.9%
NNT 111
No HF,
Riva+ASA
Time (months)

10. Major (modified ISTH) bleeding
Riva + ASA
N=9,152
ASA
N=9,126
Rivaroxaban + Aspirin
vs. Aspirin
n/N (%)
HR (95% CI) P
No HF
239/7189 (3.3)
134/7147 (1.9)
1.79 ( )
0.26 HF
49/1963 (2.5)
36/1979 (1.8)
1.36 ( )
P = p value for interaction by log-rank test by HF category

11. Net Clinical Benefit (Primary outcome + Severe bleeding events)
Riva + ASA
N=9,152
ASA
N=9,126
Rivaroxaban + aspirin
vs. aspirin
n/N (%)
HR (95% CI) P
No HF
315/7189 (4.4)
369/7147 (5.2)
0.85 ( )
0.15 HF
116/1963 (5.9)
165/1979 (8.3)
0.69 ( )
P = p value for interaction by log-rank test by HF category

12. Net Clinical Benefit: Hazard Ratios (Primary outcome + Severe bleeding events)
0.85
( )
0.69
( )
0.76
( )
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

13. Limitations
HF status was not explicitly defined or adjudicated at baseline
Restricted to mild to moderate HF at baseline
Baseline LVEF was incompletely collected (55% of patients)
Cannot define HFpEF and HFrEF
Planned analysis after additional LVEF ascertainment

14. COMPASS HF Substudy: Conclusions
Patients with chronic CAD and PAD with HF have higher event rates than those without HF
Rivaroxaban + aspirin had consistent effects on primary MACE outcome and net clinical benefit in those with HF and without HF
Absolute risk benefits are greatest in those with HF
Primary 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 trial

15. We sincerely thank all investigators, study coordinators
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