Adding Rivaroxaban to Aspirin May Help Some CAD, PAD Patients Live Longer

By Lorraine L. Janeczko

July 15, 2021

NEW YORK (Reuters Health) - Combining rivaroxaban with aspirin may help certain patients with coronary-artery disease (CAD) or peripheral-artery disease (PAD) live longer than they would with aspirin alone, a secondary analysis of the COMPASS trial suggests.

"For patients with chronic atherosclerosis, adding a small dose of rivaroxaban to aspirin not only reduces the risk of major adverse cardiovascular events, it saves lives," said lead study author Dr. John W. Eikelboom of Hamilton General Hospital in Hamilton, Canada.

The multinational COMPASS trial enrolled more than 27,000 patients with chronic CAD or PAD. Eligible participants were 65 years of age or younger with clinically stable atherosclerosis involving at least two vascular beds, or who were at risk due to smoking, diabetes, chronic kidney disease, mild or moderate heart failure, or recent nonlacunar ischemic stroke.

The COMPASS study showed that combining 2.5 mg rivaroxaban twice daily with 100 mg aspirin once daily prevented cardiovascular death, stroke, or myocardial infarction more effectively than either 100 mg aspirin per day alone or 5 mg rivaroxaban twice per day. Because the combined therapy was more effective than aspirin, the trial was stopped early, and the combination is now approved for use in this setting in many countries.

In the new analysis, Dr. Eikelboom and colleagues compared findings from 9,152 COMPASS participants who received rivaroxaban plus aspirin with those from 9,126 who received aspirin alone.

After a median follow-up of 23 months, 313 (3.4%) of patients receiving combined treatment vs. 378 (4.1%) getting aspirin alone died (hazard ratio, 0.82; P=0.01), the team reports in the Journal of the American College of Cardiology.

Combined treatment also reduced cardiovascular death, with 160 (1.7%) versus 203 (2.2%) such deaths, respectively; hazard ratio: 0.78; P=0.02). However, combined treatment did not reduce non-cardiovascular death.

Patients with higher baseline risk saw greater absolute mortality benefit. As the researchers report, those "with 0, 1, 2, and 3 or 4 high-risk features at baseline had 4.2, 4.8, 25.0, and 53.9 fewer deaths, respectively, per 1000 patients treated for 30 months."

"These results should prompt clinicians to consider routine use of low-dose rivaroxaban for long-term management of patients with atherosclerosis who are at high risk of further events," Dr. Eikelboom told Reuters Health by email.

He noted that the study included few patients with a history of stroke and lacked patients with end-stage kidney disease. "Both these populations are at very high risk and urgently require further study," he said.

"This is a well-done secondary analysis of the influential COMPASS trial," said Dr. Michael J. Blaha, a professor of medicine and the director of clinical research at the Ciccarone Center for the Prevention of Heart Disease at Johns Hopkins University in Baltimore, Maryland. "The most important part of this study is that the highest-risk patients received the most mortality benefit."

"This points to the importance of risk stratification, even in secondary prevention," Dr. Blaha, who was not involved in the study, told Reuters Health by email. "For my practice, I try to focus intensive therapy on the high-risk subsets who received the most benefit in this study - polyvascular disease, mild or moderate heart failure, chronic kidney disease, and diabetes."

In an accompanying editorial, Dr. Jonathan L. Halperin and colleagues from the Cardiovascular Institute of Mount Sinai Medical Center, in New York City, write that the authors "provide important new information that helps to identify the patients most likely to benefit from dual pathway inhibitor therapy."

"The immediate challenge is to identify patients who are likely to gain survival advantage from the specific dual pathway regimen they validated," the editorialists add. "That regimen is not appropriate for every patient with atherosclerosis, but for many of those with diabetes, involvement of more than 1 vascular bed, or ischemic heart disease underlying clinical heart failure, such treatment can begin today."

The authors recommend investigating possible survival benefits of combining the rivaroxaban with another blood thinner, ticagrelor.

Bayer, the manufacturer of aspirin and rivaroxaban, sponsored the COMPASS study. Dr. Eikelboom and several of his coauthors, as well as Dr. Halperin, have financial relationships with Bayer.

SOURCES: and Journal of the American College of Cardiology, online July 6, 2021.