Patients with stable atherosclerotic vascular disease who were treated with 2.5 mg of rivaroxaban plus aspirin had improved CV outcomes vs. aspirin alone, although they had more major bleeding events, according to the COMPASS study presented at the European Society of Cardiology Congress in Barcelona, Spain.
Results were similar in a substudy of patients with peripheral artery disease.
“The results of COMPASS represent a true breakthrough in in CAD and PAD, as they confirm the combination regimen of [rivaroxaban] and aspirin is highly effective and well-tolerated in preventing the devastating and irreversible CV events that often occur in these patients,” John W. Eikelboom, MD, associate professor in the division of hematology and thromboembolism at McMaster University in Hamilton, Ontario, Canada, said in a press release. “In addition to achieving a positive balance of efficacy and safety, we observed a considerable reduction in stroke and CV death and a reduction in all-cause mortality, which could have a profound effect on how physicians manage patients with stable CAD and PAD.”
The main findings were simultaneously published in The New England Journal of Medicine.
Researchers analyzed data from 27,395 patients (mean age, 68 years; 22% women) with CAD, PAD or both. Patients were randomly assigned 2.5 mg of rivaroxaban (Xarelto, Janssen Pharmaceuticals) twice daily plus 100 mg of aspirin once daily, 5 mg of rivaroxaban twice daily or 100 mg of aspirin once daily.
The primary efficacy outcome was a composite of stroke, CV death or MI. The main safety outcome was major bleeding as defined by a modification of the International Society on Thrombosis and Hemostasis criteria. The net-clinical-benefit outcome was CV death, MI, stroke, symptomatic bleeding into a critical organ or fatal bleeding.
After a mean follow-up of 23 months, the study was stopped for superiority.
Patients in the rivaroxaban plus aspirin group had fewer occurrences of the primary outcome compared with those assigned aspirin alone (4.1% vs. 5.4%; HR = 0.76; 95% CI, 0.66-0.86).
Major bleeding events occurred in 3.1% of patients in the rivaroxaban with aspirin group vs. 1.9% of patients assigned aspirin (HR = 1.7; 95% CI, 1.4-2.05). Fatal or intracranial bleeding did not differ between patients assigned rivaroxaban plus aspirin and those assigned aspirin alone.
The composite net-clinical-benefit outcome occurred in 4.7% of patients in the rivaroxaban plus aspirin group vs. 5.9% in those assigned aspirin alone (HR = 0.8; 95% CI, 0.7-0.91).
“Our definition of net clinical benefit balanced the lower risk of [CV] death, stroke or [MI] against the most serious bleeding events and showed a significant benefit of combination therapy,” Eikelboom and colleagues wrote in NEJM.
There was no benefit of rivaroxaban 5 mg twice daily compared with aspirin.
PAD and carotid disease findings
Sonia S. Anand, MD, PhD, FRCPC, from the department of medicine and epidemiology at McMaster University, presented an analysis of patients from COMPASS with stable PAD at ESC.
Sonia S. Anand
The analysis included 4,129 patients with symptomatic PAD, 1,919 patients with carotid disease and 1,422 patients with CAD plus ankle-brachial index < 0.9.
At a mean follow-up of 21 months, the rivaroxaban plus aspirin group had lower incidence of the primary efficacy outcome vs. the aspirin-alone group (5.1% vs. 6.9%; HR = 0.72; 95% CI, 0.57-0.9).
Compared with the aspirin-alone group, the rivaroxaban plus aspirin group also had fewer major adverse limb events (1.2% vs. 2.2%; HR = 0.54; 95% CI, 0.35-0.84) and major amputations (0.2% vs. 0.7%; HR = 0.3; 95% CI, 0.11-0.8). Compared with the aspirin-alone group, major bleeding was higher in the rivaroxaban plus aspirin group (HR = 1.61; 95% CI, 1.12-2.31). There were no significant differences between the groups in fatal or critical organ bleeding.
The composite net-clinical-benefit outcome occurred in 6.3% of patients in the rivaroxaban plus aspirin group vs. 9% of the aspirin-alone group (HR = 0.69; 95% CI, 0.56-0.85). – by Darlene Dobkowski
Anand SS, et al.
Eikelboom JW, et al. Late Breaking Clinical Trials 1. Both presented at: European Society of Cardiology Congress; August 26-30, 2017; Barcelona, Spain.
Eikelboom JW, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1709118.
Disclosure: The study was funded by Bayer. Eikelboom reports that he has received grants and personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Eli Lilly, Glaxo Smith Kline, Janssen and Sanofi Aventis. Anand reports that she has received speaking honoraria from various pharmaceutical companies. Please see the full study report for all other authors’ relevant financial disclosures.