Eikelboom JW;Connolly SJ;Bosch J;Dagenais GR;Hart Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1709118.
Area Score
Hemostasis and Thrombosis
Internal Medicine
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Hematology
Cardiology
Abstract

Background We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. Methods In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease 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). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. Results The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. Conclusions Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

I don't think this is practice-changing information. The absolute risk reduction is modest at 1.3%, giving an NNT of 77 over 2 years with an increased risk for bleeds.

General Internal Medicine-Primary Care(US) rater

I'm concerned about the benefit risk for the older old - those over 80 or 85. The numbers were small but there appeared to be less benefit and more risk for those over 75.

General Internal Medicine-Primary Care(US) rater

Short follow-up, an expensive drug, and trade-offs that should warrant shared decision-making. This begs the question of how rivaroxaban + ASA would fare against coumadin + ASA.

General Internal Medicine-Primary Care(US) rater

This is an interesting article, but the combination of rivaroxaban and aspirin, in my opinion, is not ready for prime time. I was left wondering how many people in the study had atrial fibrillation? Were we treating afib? Again, the trade-offs here are taking two extra pills, likely expensive and with potential side effects.

General Internal Medicine-Primary Care(US) rater

This is very important in clinical practice as we are making decisions to use aspirin vs NOACs. This is very helpful.

Hematology rater

This is an important study; two findings below the "topline result" stand out: (1) although all-cause mortality is lower in the riva 2.5mg + ASA arm, the NNT (for 2 years) to prevent a single death is close to 200; AND (2) the difference in the primary outcome (a composite endpoint) is driven primarily by a reduction in stroke, rather than a reduction in myocardial infarction.

Hemostasis and Thrombosis rater

An important RCT showing increased efficacy and more major bleeding with low-dose rivaroxaban plus ASA vs ASA alone in secondary prevention. The study was terminated early, which may have affected the ability to assess the impact on mortality.

Hemostasis and Thrombosis rater

Important results but a comparison with dual antiplatelet therapy would also be of interest.