Rivaroxaban plus aspirin seems beneficial in patients with moderate renal dysfunction

By Marilynn Larkin

NEW YORK (Reuters Health) - Compared with aspirin alone, rivaroxaban plus aspirin may benefit patients with vascular disease and moderate renal dysfunction, according to a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial.

COMPASS included more than 27,000 patients with chronic coronary or peripheral artery disease and showed that rivaroxaban plus aspirin was associated with fewer cardiovascular events, but more major bleeding events, than aspirin alone.

For the current study, Dr. Keith A. A. Fox of the University of Edinburgh and colleagues compared the efficacy and safety of dual therapy (rivaroxaban 2.5 mg twice daily plus aspirin) versus aspirin alone in participants with or without moderate renal dysfunction.

"The key finding...is that the absolute benefit, and the net clinical benefit, of the dual pathway therapy, versus aspirin alone, are greater in those with moderate renal dysfunction than in the study overall," Dr. Fox told Reuters Health by email. "This is because the thrombotic risks are substantially greater in those with renal dysfunction."

"However, similar rather than increased hazard ratios for bleeding were seen in those with moderate renal dysfunction," he noted.

As reported online May 6 in the Journal of the American College of Cardiology, Dr. Fox and colleagues studied 6,276 patients with an estimated glomerular filtration rate (eGFR) of 15 ml/min/1.73m2, plus 21,111 patients with an eGFR of at least 60 ml/min/1.73m2.

The primary efficacy outcome was the composite of cardiovascular death, stroke, or myocardial infarction; the primary safety outcomes were major bleeding, fatal bleeding and intracranial bleeding.

Both the primary and secondary outcomes were more frequent in those with renal dysfunction, and the frequency of the outcome events was inversely related to GFR.

However, the primary efficacy outcome was consistently less frequent with rivaroxaban 2.5 mg b.i.d. plus aspirin, regardless of GFR category.

With an eGFR of at least 60, the rate was 3.5% with rivaroxaban plus aspirin versus 4.5% with aspirin alone (hazard ratio: 0.76). With an eGFR 15, the rate was 6.4% with rivaroxaban plus aspirin versus 8.4% with aspirin alone (HR: 0.75).

The pattern was reversed for the safety outcomes, however. Major bleeding was more frequent with rivaroxaban plus aspirin when the eGFR was 60 or more (2.9%, versus 1.6% with aspirin alone; HR: 1.81) and when it was 15 (3.9% versus 2.7%; HR: 1.47).

Fatal bleeds were rare and the frequency was similar (less than 1%) between the groups, as it was for intracranial bleeds and symptomatic bleeding into a critical organ.

Dr. Fox said, "The research that still needs to be done is to test this dual pathway therapy in those with advanced or end-stage renal dysfunction."

Dr. Riyaz Bashir, Professor of Medicine at the Lewis Katz School of Medicine at Temple University and Director of Vascular and Endovascular Medicine at Temple University Hospital in Philadelphia. told Reuters Health, "The major concern I have is that the study was not designed to answer this question. Therefore, this finding is not confirmatory. This reduces the strength of the evidence."

"There are multiple more effective antiplatelet agents than aspirin that are available to treat these patients," he said by email. "Therefore, (rivaroxaban and aspirin) warrants comparison with those agents as well. The improvements seen in this study from this combination might not be replicated if the comparator were a more effective antiplatelet agent like ticagrelor alone, rather than aspirin alone."

"Physicians need to be very careful in using this combination in patients with severe renal dysfunction (GFR

The COMPASS study was funded by Bayer. Dr. Fox and three coauthors have received fees from the company.

SOURCE: https://bit.ly/2WF24Q8

J Am Coll Cardiol 2019.