Elsevier

American Heart Journal

Volume 258, April 2023, Pages 60-68
American Heart Journal

Clinical Investigations
Total events and net clinical benefit of rivaroxaban and aspirin in patients with chronic coronary or peripheral artery disease: The COMPASS trial

https://doi.org/10.1016/j.ahj.2023.01.008Get rights and content

ABSTRACT

Background

Low dose rivaroxaban with aspirin reduced major cardiovascular events (MACE) compared to aspirin alone in patients with cardiovascular disease although effects on total events are unknown.

Methods

The COMPASS clinical trial randomized 27,395 participants with chronic coronary and/or peripheral artery disease to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg daily. We analyzed total (first and recurrent) MACE outcomes of cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome of major bleeding. Exploratory analyses included on-treatment and net clinical benefit. Total MACE and safety events were modeled for each treatment.

Results

MACE events were lowest in rivaroxaban with aspirin (379 first MACE, 432 total MACE) compared with rivaroxaban (448 first, 508 total) or aspirin alone (496 first, 574 total). Rivaroxaban and aspirin reduced total MACE events compared with aspirin alone [HR 0.75, 95% CI 0.66-0.85, P < .0001, number needed to treat for 2 years (NNT2y) of 63]. Total major bleeding was higher for rivaroxaban with aspirin compared to aspirin, but severe bleeding was not increased. The net clinical benefit of rivaroxaban plus aspirin was 20% higher compared with aspirin alone [HR 0.80 (95% CI 16.3%-31.6%)]. Rivaroxaban alone had no benefit on MACE outcomes compared with aspirin alone. MACE outcomes were similar for those on and off randomized treatment.

Conclusions

Low dose rivaroxaban with aspirin significantly reduces first and total cardiovascular events compared with aspirin alone with a NNT2y of 63 and a 20% net clinical benefit.

Section snippets

Methods

COMPASS (ClinicalTrials.gov NCT01776424) was a multicenter, double blind, randomized, placebo-controlled trial of 27,395 chronic CAD and PAD patients that compared rivaroxaban 2.5 mg twice-daily plus aspirin 100 mg once-daily or rivaroxaban 5 mg twice-daily to aspirin 100 mg once-daily (rivaroxaban arm) in addition to contemporary medical therapy.8 Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as

Results

Baseline characteristics are shown in Table I. Of the 27,395 patients enrolled in COMPASS, 1,149 (4.2%) had a primary MACE event and 174 (0.6%) had more than one MACE event over the median 1.9 year follow up. Compared with the baseline characteristics of subjects that did not have a primary MACE outcome, subjects with first and recurrent MACE events were incrementally more likely to be older, hypertensive, have a history of diabetes, have a prior cardiovascular event or coronary artery disease,

Discussion

In patients with chronic CAD and/or PAD enrolled in the COMPASS trial, rivaroxaban with aspirin reduced first and total MACE events by 24% and 25%, respectively, compared with aspirin alone. The absolute risk reduction for recurrent, and therefore total, MACE events was higher than for first events thereby reducing the NNT2y of 77 for first events to NNT2y 63 for total events. The risk reductions for the components of the MACE outcomes were directionally similar for the overall findings for

Conclusions

In patients with chronic CAD or PAD, combination rivaroxaban 2.5 mg BID with aspirin compared with aspirin monotherapy produced similar relative risk reduction but larger absolute risk reduction in total MACE outcomes as compared with first MACE outcomes. The number needed to treat to prevent a first MACE of 77 was reduced to 63 to prevent a first and recurrent MACE outcome. The resultant 20% net clinical benefit of combined rivaroxaban and aspirin treatment demonstrate persistent reduction in

Funding

The COMPASS trial was sponsored by a grant from Bayer to Population Health Research Institute who conducted the trial. The authors have full control and oversight of the data, data analyses, and submission of the manuscript.

Disclosures

Kelley Branch discloses the following: Advisory Boards: Janssen, Bayer. Consultation: Janssen, Bayer, Kestra, Sana, Amgen. Research Support: NIH, Population Health Research Institute, Bayer, Sanofi, Kestra, Eli Lilly.

Jeffrey Probstfield discloses the following: Research support: Bayer.

John Eikelboom reports grants and personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Janssen, Astra Zeneca, Eli Lilly, Glaxo Smith Kline, and Sanofi Aventis

Dr. Deepak L.

CRediT authorship contribution statement

Kelley R.H. Branch: Conceptualization, Methodology, Investigation, Writing – original draft, Writing – review & editing. Jeffrey L. Probstfield: Conceptualization, Investigation, Writing – original draft, Writing – review & editing. Jackie Bosch: Conceptualization, Methodology, Investigation, Data curation, Writing – review & editing, Supervision, Project administration. Deepak L. Bhatt: Conceptualization, Methodology, Investigation, Writing – review & editing, Supervision. Aldo P. Maggioni:

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This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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