‘Tis the Season for a Festive Direct Oral Anticoagulant Update

Volume 10, Issue 4

Happy holidays everyone, and Merry Christmas to those who celebrate. In searching for a holiday-themed topic, I couldn’t think about anything more festive than anticoagulation in atrial fibrillation.

Direct oral anticoagulants (DOACs) have largely supplanted warfarin as the agents of choice for stroke prevention, with apixaban and rivaroxaban capturing most of the market share. No direct randomized clinical trials have been done comparing these agents, leaving ambiguity and equipoise over which agent should be preferred.

In this week’s installment of Talking Therapeutics, we review a recently published paper exploring the outcomes of rivaroxaban versus apixaban.

Point 1: Apixaban Appears Superior

A retrospective cohort study was conducted using computerized enrollment and claims files for US Medicare beneficiaries 65 years of age or older. Between January 1, 2013, and November 30, 2018, a total of 581,451 patients with atrial fibrillation began rivaroxaban or apixaban treatment. Follow up was 4 years, through November 30, 2018. The primary outcome was a composite of major ischemic (stroke, systemic embolism) and hemorrhagic (intracerebral hemorrhage, other intracranial bleeding/fatal extracranial bleeding) events.

The rivaroxaban group had increased risk for both major ischemic events (8.6 vs 7.6 per 1000 person-years; RD, 1.1 [95% CI, .5-1.7]; HR, 1.12 [95% CI, 1.04-1.20]) and hemorrhagic events (7.5 vs 5.9 per 1000 person-years; RD, 1.6 [95% CI, 1.1-2.1]; HR, 1.26 [95% CI, 1.16-1.36]), including fatal extracranial bleeding. Patients receiving rivaroxaban had increased risk of nonfatal extracranial bleeding, fatal ischemic/hemorrhagic events, and total mortality.

Of the overall cohort, 23% of patients were taking a reduced dose of either medication; these patients tended to be older and have more comorbidities than the standard dose group. Similar to the overall cohort, the risk of the major ischemic and hemorrhagic events was increased for those receiving the reduced dose of rivaroxaban.

Point 2: Important Strengths and Limitations of This Analysis

Several other retrospective cohort studies have compared these two DOACs, but this new paper stands out in several important ways.

First, the cohort is larger than those of previous studies and consisted entirely of patients 65 years of age or older, who have both the highest incidence of atrial fibrillation and greatest risk of major ischemic or hemorrhagic events. The greater sample size permits more precise quantification of the occurrence of infrequent but clinically important events, such as fatal extracranial bleeding.

Second, in contrast to other studies, the cohort included patients treated with reduced doses, whose baseline comorbidity indicated greater susceptibility to differences in anticoagulant efficacy and safety.

While these features certainly fortify the results of this study, it is still a nonrandomized retrospective analysis, which prohibits a firm conclusion of causality between the DOAC exposure and the outcomes of interest. Nevertheless, the sheer size of this analysis points to a very strong association between apixaban use and improved clinical outcomes in elderly atrial fibrillation patients.