A large real-world study supports the safety and effectiveness of direct oral anticoagulants (DOACs) in patients with valvular atrial fibrillation (AF). In this patient population, compared with new users of warfarin, new users of DOACs had lower risks for ischemic stroke or systemic embolism and major bleeding events, in a comparative effectiveness published in Annals of Internal Medicine. "The results from this large observational analysis support the use of DOACs in patients with valvular AF for the prevention of ischemic stroke or systemic embolism without concerns regarding adverse bleeding complications," Dr. Ghadeer Dawwas, from the Perelman School of Medicine at the University of Pennsylvania, told Reuters Health by email. There has been rapid uptake of DOACs in patients with nonvalvular AF and DOACs are now recommended first-line options in international guidelines. However, evidence about their effectiveness and safety in patients with valvular AF remains limited. "Randomized clinical trials that evaluated the efficacy and safety of DOACs in patients with AF excluded or underrepresented patients with valvular heart diseases. This subpopulation of AF is at an increased risk of adverse outcomes since valvular heart diseases increase the risk of stroke independent of AF," Dr. Dawwas told Reuters Health. To investigate, the researchers used a healthcare database to create a propensity-matched cohort of adults with valvular atrial fibrillation who were newly prescribed a DOAC (apixaban, dabigatran, edoxaban, or rivaroxaban) or warfarin, between January 2010 and June 2019. There were 28,168 in each group. Over the study period, DOAC users had a lower risk for ischemic stroke or systemic embolism (hazard ratio, 0.64; 95% confidence interval: 0.59 to 0.70) and major bleeding events (HR, 0.67; 95% CI: 0.63 to 0.72), they report. "Subgroup analyses suggest that the observed benefits of DOACs over warfarin extend across age and other factors," they note. "In addition, results were largely consistent for the different DOACs except for a nonsignificant effectiveness benefit for dabigatran over warfarin. These findings are consistent with those of another small study, but whether this observed benefit is due to the small number of patients receiving dabigatran or a true difference in effectiveness is uncertain," they write. Dr. Dawwas told Reuters Health, "A large proportion of valvular AF patients enrolled in the study were new-users of apixaban or rivaroxaban. For the within-class comparisons of individual DOACs (vs. warfarin), the analyses included 19,136 apixaban users, 12,851 rivaroxaban users, and only 3,535 dabigatran users. Due to the limited sample size, it remains unclear if the dabigatran analysis is underpowered or represents a true difference in effectiveness." "These findings have important clinical implications for patients with valvular AF who are at risk for poor outcomes; DOACs provide treatment options in patients who receive suboptimal benefits from warfarin therapy," they conclude. Weighing in on the study for Reuters Health, Dr. Vivek Reddy, Director of Cardiac Arrhythmia Services for The Mount Sinai Health System in New York said, "Overall, this seems like a reasonable manuscript (i.e., well done, good methodology, appropriate conclusions)." Because of the advantages demonstrated in randomized trials, DOACs have largely replaced warfarin as first-line stroke prophylaxis in nonvalvular AF, Dr. Reddy noted in his email. "This manuscript addresses the population of patients with valvular AF. While there is little randomized data in this valvular AF population, this propensity-matched analysis from a very large database indicates that DOACs also work better than warfarin in this population," Dr. Reddy said. "While there has been some shift in using DOACs in the valvular AF population, this is additional data that will probably accelerate that shift," he said. "But just to be clear, the definition of valvular is important," he said. "There remains a population of valvular AF that was not studied here - specifically, patients with mechanical valves. In this population, warfarin still remains the gold standard and this will probably remain the case." —Megan Brooks Source
