Direct oral anticoagulants safe, effective in patients with valvular AF
Patients with valvular atrial fibrillation who recently began using direct oral anticoagulants had a lower risk for systemic embolism or ischemic stroke and major bleeding compared with new warfarin users, an analysis showed.
More than 5.2 million Americans experience atrial fibrillation (AF) annually, with 158,000 of them succumbing to the condition. Atrial fibrillation also increases an individual’s risk for stroke, Ghadeer K. Dawwas, PhD, MSc, MBA, a postdoctoral research fellow in the department of biostatistics, epidemiology and informatics at Perelman School of Medicine at the University of Pennsylvania, wrote in Annals of Internal Medicine.
Reported drawbacks to warfarin, a “mainstay therapy” in stroke prevention, include a “narrow therapeutic window, dose-response variability and many interactions with drugs and food,” according to the researchers.
Conversely, direct oral anticoagulants (DOAC) have fairly short half-lives, fewer interactions with other drugs, no interactions with food, easier-to-manage dosing, and do not require laboratory monitoring on a routine basis, the researchers continued.
In previous randomized clinical trials, DOAC use demonstrated “similar or superior antithrombotic effects to warfarin” in patients with AF, the researchers wrote. However, these trials “excluded or underrepresented patients with valvular heart diseases,” Dawwas told Healio Primary Care.
“The current population‐based analysis using large commercial data in the United States focused on patients with AF and concomitant valvular abnormalities. This subpopulation of AF is at an increased risk of adverse outcomes since valvular heart diseases increase the risk of stroke independent of AF,” she said.
Dawwas and colleagues conducted a retrospective new-user retrospective propensity score-matched cohort study with data on 56,336 patients with valvular AF that were collected from Jan. 1, 2010, to June 30, 2019. Most patients were aged in their 70s or 80s and about half were men.
The researchers matched DOAC users with warfarin users based on propensity scores. Patients were followed until the end of the study, or until they temporarily or permanently stopped receiving treatment; switched treatment; experienced one of the study outcomes — which included occurrence of ischemic stroke, systemic embolism and/or intracranial or gastrointestinal bleeding — or until disenrollment.
The researchers reported that DOAC use, when compared with warfarin use, was associated with a lower risk for major bleeding events (HR = 0.67; 95% CI, 0.63-0.72) and ischemic stroke or systemic embolism (HR = 0.64; 95% CI, 0.59-0.7). The safety and effectiveness outcomes of the DOAC apixaban (HR = 0.52; 95% CI, 0.47-0.57 and HR = 0.54; 95% CI, 0.47-0.61, respectively) closely aligned with those of the DOAC rivaroxaban (HR = 0.87; 95% CI, 0.79-0.96 and HR = 0.74; 95% CI, 0.64-0.86, respectively). Although the major bleeding outcome for the DOAC dabigatran was comparable to warfarin (HR = 0.81; 95% CI, 0.68-0.97), it did not demonstrate similar effectiveness (HR = 1.03; 95% CI, 0.81-1.31).
“Results were largely consistent for the different DOACs except for a nonsignificant effectiveness benefit for dabigatran over warfarin,” the researchers wrote. “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.”
Dawwas noted that the study was limited in that it had a “relatively short” follow-up and the severity of patients’ valvular AF was unknown; however, the findings are still important.
“The results from this large observational analysis support the use of DOAC in patients with valvular AF for the prevention of ischemic stroke or systemic embolism without concerns regarding adverse bleeding complications,” Dawwas said.