Compared to warfarin, all direct oral anticoagulants (DOACs) were associated with fewer cardiovascular events including heart attacks and strokes in a study of Medicare patients with both nonvalvular atrial fibrillation and heart failure. But apixaban appeared to offer the best balance of protecting against these events while minimizing bleeding risk.
Alpesh Amin, MD, MBA, with the University of California, Irvine, and colleagues used Medicare and pharmacy claims data to study thousands of patients with nonvalvular AFib (NVAF) and heart failure who filled a prescription for warfarin or a DOAC from January 2012 through September 2015. They used propensity-score matching to compare one medication to another as far as their associations with stroke/systemic embolism, major bleeding and major adverse cardiovascular events (MACE)—which included myocardial infarction, stroke and all-cause mortality—over average follow-up periods of six to eight months.
The researchers matched 10,570 patients taking warfarin against the same number taking apixaban. They found those prescribed the DOAC had 36 percent lower odds of stroke/systemic embolism, 34 percent lower odds of major bleeding and 27 percent lower odds of MACE.
Propensity-matched pairs of patients taking dabigatran and rivaroxaban—versus warfarin in both cases—found those DOACs were also associated with 13 to 16 percent lower likelihoods of MACE. Rivaroxaban also had a lower rate of stroke or systemic embolism but an 18 percent higher major bleeding risk than warfarin.
When apixaban users were compared to more than 10,000 patients taking rivaroxaban and 4,263 taking dabigatran, apixaban showed better results. Those patients had a 45 percent lower risk of bleeding and a 14 percent lower risk of MACE versus rivaroxaban, and the corresponding risk reductions compared to dabigatran were 29 percent and 20 percent.
Amin et al. said the results of the real-world analysis are mostly in line with those observed in studies.
“There are no head-to-head randomized control trials comparing DOACs among NVAF patients; real-world comparative studies of DOACs exist and are increasing in number as the use of these medications becomes more widespread,” they wrote in PLOS One. “These studies have shown that apixaban use is associated with similar or lower rates of stroke/SE and lower rates of (major bleeding) compared to dabigatran and rivaroxaban.”
The authors said their study was limited by its retrospective, observational design, which eliminates the ability to establish causality. Also, a large proportion of patients had unspecified heart failure, so they were unable to determine whether there were different treatment effects for patients with heart failure with preserved ejection fraction versus reduced ejection fraction.
Finally, there were fewer dabigatran users in the study population than those taking other anticoagulants, making for wider confidence intervals and the need to interpret the dabigatran results with caution, the authors noted.
Nonetheless, “findings from this observational analysis provide important insights regarding the use of OAC therapy among patients with comorbid NVAF and HF in a real-world setting,” Amin and colleagues wrote.
The study was funded by Bristol-Myers Squibb and Pfizer, the manufacturers of apixaban. Many of the authors reported receiving research salaries or consultant fees from the companies.