The document discusses the efficacy of dual therapy with aspirin and rivaroxaban for patients with cardiovascular diseases, referencing various studies including the COMPASS trial. It highlights the benefits of combining these medications in reducing cardiovascular events and mortality among high-risk patients, such as those with polyvascular disease and chronic conditions. Additionally, the document outlines the risks of major bleeding associated with this combination therapy.

1. Dual Therapy with
Aspirin and Rivaroxaban
Peter Verhamme
Dept. Cardiovascular Sciences
KU Leuven – Belgium

2. Disclosures Peter Verhamme
COMPASS Steering Committee
Honoraria for lectures from
Bayer, Boehringer, BMS, Pfizer, Daiichi Sankyo, Portola

3. 1. Combining Oral Anticoagulation and Antiplatelet therapy?
2. COMPASS trial
3. Identifying the high-risk patient

4. Combining Oral Anticoagulation and Antiplatelet therapy?
• Warfarin is more effective than aspirin / when added to aspirin in
post-MI patients
• Rivaroxaban is effective when added to DAPT in post-ACS
patients (ATLAS ACS 2 – TIMI 51)
Mega J, et al. N Engl J Med 2012; 366: 9-19. ATLAS ACS 2 – TIMI 51
Andreotti F, et al. Eur Heart J 2006; 27: 519-26. Anand S, et al. J Am Coll Cardiol 2003; 41: 62S-69S.

5. COMPASS trial
R
Rivaroxaban 2.5 mg bid
+ Aspirin 100 mg od
Aspirin 100 mg od
Rivaroxaban 5 mg bid
Expected mean follow up: 3-4 years
27,395 patients with Stable CAD or PAD
2,200 participants with a primary outcome event
Bosch JJ, et al. Can J Cardiol 2017; 33: 1027-1035.

6. COMPASS trial in patients with CAD or PAD:
Primary outcome
Eikelboom JW, et al. N Engl J Med 2017; 377: 1319-30.

7. COMPASS trial in patients with CAD or PAD:
Primary outcome
Eikelboom JW, et al. N Engl J Med 2017; 377: 1319-30.

8. COMPASS trial in patients with CAD or PAD:
Primary outcome
Eikelboom JW, et al. N Engl J Med 2017; 377: 1319-30.

9. Components of primary outcome
0
1
2
3
4
5
6
Overall CV Death Stroke MI
%Events
Riva + Aspirin
Aspirin
HR 0.78
95% CI, 0.64-0.96
HR 0.58
95% CI, 0.44-0.76
HR 0.86
95% CI, 0.70-1.05
HR 0.76
95% CI, 0.66-0.86
Eikelboom JW, et al. N Engl J Med 2017; 377: 1319-30.

10. Acute coronary events
0
0,5
1
1,5
2
2,5
3
3,5
4
MI MI, SCD MI, SCD, arrest
%Events
Riva + aspirin
aspirin
HR 0.85
95% CI: 0.72-1.00
HR 0.81
95% CI: 0.69-0.95
HR 0.86
95% CI: 0.70-1.05
Eikelboom JW, et al. N Engl J Med 2017; 377: 1319-30.

11. CAD patients: consistent benefits irrespective of time
since previous MI
Connolly SJ, et al. Lancet 2018; 391: 205-18.

12. CumulativeHazardRate
0.00.020.040.060.080.10
0 1 2 3
9152 7858 3880 646
9117 7841 3869 661
9126 7874 3938 681
No. at Risk
Rivaroxaban + Aspirin
Rivaroxaban
Aspirin
Rivaroxaban + Aspirin
Rivaroxaban
Aspirin
Rivaroxaban + Aspirin vs. Aspirin HR: 1.70 (1.40-2.05) P=<0.0001
Rivaroxaban vs. Aspirin HR: 1.51 (1.25-1.84) P=<0.0001
Major BleedingMajor Bleeding

13. CumulativeHazardRate
0.00.020.040.060.080.10
0 1 2 3
9152 7858 3880 646
9117 7841 3869 661
9126 7874 3938 681
No. at Risk
Rivaroxaban + Aspirin
Rivaroxaban
Aspirin
Rivaroxaban + Aspirin
Rivaroxaban
Aspirin
Rivaroxaban + Aspirin vs. Aspirin HR: 1.70 (1.40-2.05) P=<0.0001
Rivaroxaban vs. Aspirin HR: 1.51 (1.25-1.84) P=<0.0001
Major BleedingMajor Bleeding

14. CumulativeHazardRate
0.00.020.040.060.080.10
0 1 2 3
9152 7858 3880 646
9117 7841 3869 661
9126 7874 3938 681
No. at Risk
Rivaroxaban + Aspirin
Rivaroxaban
Aspirin
Rivaroxaban + Aspirin
Rivaroxaban
Aspirin
Rivaroxaban + Aspirin vs. Aspirin HR: 1.70 (1.40-2.05) P=<0.0001
Rivaroxaban vs. Aspirin HR: 1.51 (1.25-1.84) P=<0.0001
Major BleedingMajor Bleeding

15. Sites of major bleeding
Outcome
Riva + aspirin
N=9,152
Aspirin
N=9,126
Rivaroxaban +
aspirin vs. aspirin
N % N % HR 95% CI P
Intracranial 28 0.3 24 0.3 1.16 0.67-2.00 0.60
Gastrointestinal 140 1.5 65 0.7 2.15 1.60-2.89 <0.0001
Urinary 13 0.1 21 0.2 0.61 0.31-1.23 0.16
Eye 22 0.2 13 0.1 1.68 0.85-3.34 0.13
Skin/injection site 28 0.3 12 0.1 2.31 1.18-4.54 0.01

16. www.phri.ca
Association between gastrointestinal bleeding and
gastrointestinal cancer
Population
Total
N
New GI cancers
(n=212) HR
(95% CI)
P value
N %
GI bleeding
After bleeding 905* 67 7.4 20.6
(15.2-27.8)
<0.0001
No prior bleeding 27,395 145 0.5
*Excludes patients with bleeding who were diagnosed with cancer before the bleeding event
Eikelboom JW, et al. Circulation 2019;140:1451-1459.

17. www.phri.ca
1. Combining Oral Anticoagulation and Antiplatelet therapy?
2. COMPASS trial
3. Identifying the high-risk patient

18. Cardiovascular disease: who derives the greatest
benefit from the COMPASS regimen?
• Polyvascular disease
• Mild or moderate heart failure
• Chronic kidney disease
• Diabetes
• Multiple risk factors
Anand S, et al. J Am Coll Cardiol 2019;73:3271-3280.
Vanassche T, et al. Eur J Prevent Cardiol 2019

19. Regression tree analysis to identify high risk groups
Anand S, et al. J Am Coll Cardiol 2019;73:3271-3280.

20. Cardiovascular drugs at baseline
Vanassche T, Verhamme P, et al. submitted

21. Cardiovascular risk factors at baseline
BP control (y/n), cholesterol control (y/n), BMI elevated (y/n),
Physical Activity (y/n), Smoking (y/n), Diabetes (y/n)
Vanassche T, Verhamme P, et al. Eur J Prevent Cardiol 2019

22. Cardiovascular disease: who derives the greatest
benefit from the COMPASS regimen?
• Polyvascular disease
• Mild or moderate heart failure
• Chronic kidney disease
• Diabetes
• Multiple risk factors
Anand S, et al. J Am Coll Cardiol 2019;73:3271-3280.
Vanassche T, et al. Eur J Prevent Cardiol 2019

23. COMPASS regimen is the first long-term
antithrombotic since ASA to reduce mortality
*Not significant. †Major coronary event. ‡Gastrointestinal bleeding. §Non-fatal. ¶severe and moderate GUSTO bleeding, respectively
1. Antithrombotic Trialists’ Collaboration. Lancet 2009; 2: 172–183. 2. CAPRIE Investigators. Lancet 1996; 348: 1329-39.
3. Bhatt DL, et al. N Engl J Med 2006 Apr 20;354(16):1706-17. 4. Bonaca MP, et al. N Engl J Med 2015; 372: 1791-800.
5. Eikelboom JW, et al. N Engl J Med 2017; 377:1319–30.
ASA1
(ATTC)
Clopidogrel2
(CAPRIE)
ASA +
clopidogrel3
(CHARISMA)
ASA +
ticagrelor4
(PEGASUS)
ASA +
Rivaroxaban5
(COMPASS)
MACE –19% –9% –7%* –16% –24%
Stroke +18%* NA -21%§ –25% –42%
MI –20%† NA -6%§* –16% –14%*
Bleeding +69% -25% +25-62%¶ +132% +70%
Death –10% –2%* –1%* –11%* –18%

24. www.phri.ca
1. Combining Oral Anticoagulation and Antiplatelet
therapy?
2. COMPASS trial
3. Identifying the high-risk patient