Apixaban Trumps Other DOACs in Comparative Analysis of More than 500k AFib Patients

Wallis Lau, PhD

Results of analysis comparing the bleeding risk of apixaban, dabigatran, edoxaban, and rivaroxaban among people with atrial fibrillation (AF) suggests apixaban was associated with the lowest risk of gastrointestinal bleeding and similar rates of thromboembolic events compared with other direct oral anticoagulants (DOACs).

With data from 5 centralized electronic health record databases encompassing more than 221 million individuals in Europe and the United States, including more than 500,000 new DOAC users, results of the analysis offer clinicians with what could be the most comprehensive overview yet of the comparative safety of these agents within the class among people with AF.

“Direct oral anticoagulants have been prescribed with increasing frequency worldwide in recent years, but evidence comparing them directly has been limited,” said study investigator Wallis Lau of the University College of London School of Pharmacy, in a statement. “Our results indicate that apixaban may be preferable to other blood thinners because of the lower rate of gastrointestinal bleeding and similar rates of stroke, a finding that we hope will be supported by randomized controlled trials.”

With inclusion in recent guidelines, DOACs have begun to replace warfarin as the preferred anticoagulation choice for most patients with AF in the US. Much to the chagrin of patients and providers, the advent of the DOAC class brought forth multiple pharmacotherapies, but this has led to questions regarding the comparative efficacy and safety of these agents. Citing the lack of a randomized controlled trial directly comparing the agents within the class, Lau and a team of colleagues sought to conduct a large-scale comparison between apixaban, dabigatran, edoxaban, and rivaroxaban in real-world practice.

Investigators designed a multinational, population-based cohort study using data provided by IQVIA, which provided investigators with electronic health record databases from France, Germany, the United Kingdom, and the United States. For inclusion in the study, individuals needed to have AF, be 18 years of age or older, and have no reported DOAC use. From the databases, investigators obtained information related to more than 221 million individuals. Among these, 527,226 new DOAC users were identified for inclusion in the investigators’ analysis, including 281,320 users of apixaban, 61,008 users of dabigatran, 12,722 users of edoxaban, and 172,176 users of rivaroxaban.

The study had 4 outcomes of interest, which were gastrointestinal bleeding, a composite of ischemic stroke and systemic embolism, intracranial hemorrhage (ICH), and all-cause mortality. Investigators used Cox regression models stratified by propensity score and pooled using a random-effects model to assess risk of each outcome.

Upon analysis, results indicated use of apixaban was associated with a lower risk of gastrointestinal bleeding than dabigatran (HR, 0.81 [95% CI, 0.70-0.94]), edoxaban (HR, 0.77 [CI, 0.66-0.91]), or rivaroxaban (HR, 0.72 [CI, 0.66-0.79]). Investigators highlighted no substantial differences were observed for the other outcomes of interest. Further analysis stratified by patient age indicated these results were consistent among those aged 80 years or older. Investigators also pointed out consistent associations were observed between lower gastrointestinal bleeding risk and apixaban versus rivaroxaban among those receiving the standard dose (HR, 0.72 [95% CI, 0.64-0.82]), those receiving a reduced dose (HR, 0.68 [95% CI, 0.61-0.77]), and those with chronic kidney disease (HR, 0.68 [95% CI, 0.59-0.77]).

Investigators cautioned against overinterpretation of the results from their study, citing the possibility of residual confounding as an inherent limitation.

“As with all medications, potential risks and benefits can differ between people, so considering the full spectrum of outcomes and side effects will still be necessary for each individual patient,” Lau added, in the aforementioned statement.

This study, “Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation,” was published in the Annals of Internal Medicine.