Rivaroxaban Plus Aspirin Benefits Patients with Stable CAD

By Marilynn Larkin

NEW YORK (Reuters Health) – Adding rivaroxaban to aspirin significantly reduced morbidity and mortality in patients with stable coronary artery disease (CAD), although it did increase major gastrointestinal bleeding, researchers say.

The effects of the Factor Xa inhibitor anticoagulant drugs apixaban and rivaroxaban have been studied in patients after acute coronary syndrome (ACS). Specifically, the ATLAS 2 study (https://bit.ly/Kyaz9M) showed that in patients stabilized after ACS, oral rivaroxaban (2.5 mg or 5 mg twice daily) significantly reduced the incidence of myocardial infarction when the drug was given in conjunction with (mostly dual) antiplatelet therapy.

The current study, COMPASS, tested rivaroxaban and aspirin in combination and against each other in patients with stable CAD, most of whom had experienced a heart attack and had surgery or stent procedures years earlier.

Dr. Stuart Connolly of McMaster University and Hamilton Health Sciences in Hamilton, Ontario, Canada, and his colleagues conducted a multicenter, randomized-controlled trial of patients with stable CAD or peripheral artery disease in 33 countries. Participants were enrolled from March 2013 through May 2016.

The current article reports on the 24,824 patients with CAD (mean age 69; 20% women), who made up about 90% of participants and were followed for a mean of two years.

A total of 17,028 patients (69%) had a history of previous myocardial infarction, of which 1,238 (5%) had occurred within one year of enrollment; 7,234 (29%) between one and five years before enrollment; and 8,520 (34%) more than five years before enrollment.

Participants were randomly assigned to receive oral rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily); rivaroxaban alone (5 mg twice daily); or aspirin alone (100 mg once daily).

As reported in The Lancet, online November 10, the combination of rivaroxaban plus aspirin reduced major cardiovascular events by 26%, including stroke by 44%, and mortality by 23% compared with aspirin alone.

In contrast, treatment with rivaroxaban alone did not significantly improve major cardiovascular events when compared with aspirin alone.

Article continues on page 2

A post-hoc analysis of patients with more stable clinical symptoms, defined as those without a myocardial infarction or revascularization procedure during the two years before enrollment, showed a similar benefit from adding rivaroxaban to aspirin as in those who had experienced one of those events in the past two years.

Rivaroxaban plus aspirin increased major bleeding by 66% compared with aspirin alone, whereas rivaroxaban alone increased major bleeding by 51%. However, the most common site of major bleeding was gastrointestinal, the authors note, and there was no significant increase in intracranial or fatal bleeding.

“COMPASS has extended the positive results of ATLAS 2, showing that addition of rivaroxaban to aspirin is effective with an acceptable bleeding risk,” the authors state. “The observation that the benefit of adding rivaroxaban to aspirin was consistent, both in patients with more recent events and in patients with cardiovascular events many years previously, indicates that rivaroxaban will be useful over long periods of treatment.”

In an email to Reuters Health, Dr. Connolly said “physicians may want to choose higher-risk patients when they initially start to use rivaroxaban, but our study shows that the relative risk reduction is quite consistent across a wide range of patients and across the spectrum of risk.”

What about cost?

“Physicians need to be concerned about the cost-effectiveness of therapies and can discuss this with patients as appropriate to each individual case,” he said. “The COMPASS cost analysis is not yet fully completed, and as yet we do not know the price of this dose of rivaroxaban in most countries," including the United States, where it is not yet approved for this indication.

Dr. Magnus Ohman of Duke University School of Medicine in Durham, North Carolina, author of an accompanying editorial, told Reuters Health in an email, ”These results are important, as they show clearly that there are opportunities for secondary prevention, particularly for high-risk patients such as those with polyvascular disease (coronary artery disease with peripheral artery disease or cerebrovascular disease).”

In his editorial, he noted, “Patients with stable polyvascular disease have high event rates in the outpatient setting. . . . Unfortunately, the use of and adherence to secondary prevention in these patients have been suboptimal. . . . A potential 25% relative reduction in cardiovascular events in these high-risk patients, who are in general underserved, would be a great advance in the field of secondary prevention.”

Dr. Sripal Bangalore, an interventional cardiologist at NYU Langone Health in New York City, told Reuters Health by email that patients “absolutely” might resist taking an additional drug if their disease is stable.

“It will take patient education about the risk of future cardiovascular events and this strategy of adding low dose rivaroxaban to aspirin to reduce the risk of cardiovascular events and death,” he concluded.

The study was funded by Bayer, which markets rivaroxaban with Johnson & Johnson in the United States. Dr. Connolly and 10 coauthors received funds from Bayer, and two were employees during the study.

SOURCES: https://bit.ly/2hALYEq and https://bit.ly/2j6fj9M

Lancet 2017.

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