Rivaroxaban Increased Risk of Major Ischemic, Hemorrhagic Events In AFib Treatment

Wayne A. Ray, PhD

As atrial fibrillation is known to increase the risk of stroke 5-fold, anticoagulation in the prevention of ischemic stroke is critical, so differences in the clinical outcomes of rivaroxaban and apixaban may result in major health implications.

A recent retrospective cohort study compared major ischemic and hemorrhagic outcomes in Medicare beneficiaries with atrial fibrillation who started anticoagulation treatment with rivaroxaban or apixaban.

Thus, led by Wayne A. Ray, PhD, Department of Health Policy, Vanderbilt University School of Medicine, a team of investigators found treatment with rivaroxaban compared with apixaban was associated with a significantly increased risk of major ischemic or hemorrhagic events.

Methods

Data in the study included computerized enrollment and claims files for US Medicare beneficiaries 65 years or older with fee-for-service and prescription drug coverage.

These patients provided demographic information and filled a prescription for apixaban or rivaroxaban with either the standard (5 mg twice daily or 20 mg once daily, respectively) or reduced (2.5 mg twice daily or 15 mg once daily, respectively) dose for atrial fibrillation.

Patients were enrolled between January 2013 - November 2018 and followed up for up to 4 years, starting the day following the initial oral anticoagulant prescription.

The primary study outcome was defined as a composite of major ischemic or hemorrhagic events, including ischemic stroke, systemic embolism, hemorrhagic stroke, other intracranial bleeding, and fatal extracranial bleeding.

In the analysis, rates, hazard ratios (HRs), and rate differences (RDs) were adjusted for baseline differences in comorbidity with inverse probability of treatment weighting.

Findings

A total of 581,451 patients with atrial fibrillation initiated oral anticoagulant treatment, including 227,572 patients in the rivaroxaban group and 353,879 in the apixaban group.

These patients had a mean age of 77.0 years, while 291,966 (50.2%) were women and 134,393 (32.1%) were receiving the reduced anticoagulant dose. There were a total of 474,605 person-years of follow-up, with median followup of 174 days for rivaroxaban and 176 for apixaban.

Data show the risk of the primary outcome was greater for rivaroxaban with an adjusted rate of 16.1 per 1000 person-years compared to 13.4 per 1000 person-years for apixaban (RD, 2.7, 95% CI, 1.9 - 3.5; HR, 1.18, 95% CI, 1.12 - 1.24).

Further, the rivaroxaban group had increased risk for both major ischemic events (8.6 versus 7.6 per 1000 person-years; RD, 1.1, 95% CI, 0.5 - 1.7; HR, 1.12, 95% CI, 1.04 - 1.20) and major hemorrhagic events (7.5 versus 5.9 per 1000 person-years; RD, 1.6, 95% CI, 1.1 - 2.1; HR, 1.26, 95% CI, 1.16 - 1.36). This included fatal extracranial bleeding (1.4 versus 1.0 per 1000 person-years; RD, 0.4, 95% CI, 0.2 - 0.7; HR, 1.41, 95% CI, 1.18 - 1.70).

Additionally, patients receiving rivaroxaban had an increased risk of nonfatal extracranial bleeding (39.7 versus 18.5 per 1000 person-years; RD, 21.1, 95% CI, 20.0 - 22.3; HR, 2.07, 95% CI, 1.99 - 2.15) and fatal ischemic/hemorrhagic events (4.5 versus 3.3 per 1000 person-years; RD, 1.2, 95% CI, 0.8 - 1.6; HR, 1.34, 95% CI, 1.21 - 1.48).

Ray and colleagues noted the risk of the primary outcome was increased for rivaroxaban in both patients receiving the reduced dose (27.4 versus 21.0 per 1000 person-years; RD, 6.4, 95% CI, 4.1 - 8.7; HR, 1.28, 95% CI, 1.16 - 1.40) and the standard dose (13.2 versus 11.4 per 1000 person-years; RD, 1.8, 95% CI, 1.0 - 2.6; HR, 1.13, 95% CI, 1.06 - 1.21).

Takeaways

Investigators pointed to an increased sample size, treatment with reduced doses, and an integrated measure of the benefits and harms of anticoagulation for patients with atrial fibrillation as the 3 distinct contributions of evidence necessary to guide clinical practice.

“Although the incidence of major ischemic or hemorrhagic events was increased for patients receiving rivaroxaban in either dose, both the relative and absolute increase in risk were most pronounced for those with reduced doses, which underscores the importance of anticoagulant choice in this population,” they wrote.

The study, “Association of Rivaroxaban vs Apixaban With Major Ischemic or Hemorrhagic Events in Patients With Atrial Fibrillation,” was published in JAMA.