Benefit-Risk Assessment of Rivaroxaban in Older Patients With Nonvalvular Atrial Fibrillation or Venous Thromboembolism.

Background: Both bleeding and adverse ischemic events increase with age, compounding the benefit-risk balance of anticoagulants in older patients. We present analyses using benefit-risk methods to better understand the age-dependence of the benefit-risk profile of rivaroxaban in patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE).

Methods: Randomized controlled trial data from the ROCKET-AF (NVAF) and EINSTEIN DVT, EINSTEIN PE, EINSTEIN-Extension, and EINSTEIN CHOICE in (VTE) were used. For ROCKET-AF, benefits and risks were assessed with incidence rates for key thrombotic and bleeding endpoints and a net clinical benefit (NCB) measure. Cumulative incidences (estimated by the Kaplan-Meier method) were estimated at day 185 for EINSTEIN and EINSTEIN Extension and 1 year for EINSTEIN CHOICE. Incidence differences were calculated for the overall population and age subgroups of < 65, 65-75, and > 75 years.

Results: In ROCKET-AF, rate differences in the composite NCB outcome (vascular death, stroke, myocardial infarction, fatal bleeding, critical organ bleeding, and non-CNS systemic embolism) favored rivaroxaban overall and by age < 65, 65-75, and > 75 years (-84, -25, -61, and -150 cases per 10,000 patient-years, respectively). In the pooled EINSTEIN DVT and EINSTEIN PE studies, cumulative incidence differences for the composite NCB outcome (recurrent VTE and major bleeding) were -103, 3, -105, and -544 per 10,000 patients, respectively. For extended VTE treatment with rivaroxaban versus placebo in EINSTEIN-Extension, NCB results were -536, -492, -556, and -601 per 10,000 patients, respectively. In the EINSTEIN CHOICE analysis, NCB favored rivaroxaban 20 mg versus aspirin (-284, -255, -339, and -338, respectively) and rivaroxaban 10 mg versus aspirin (-339, -328, -485, and -80, respectively).

Conclusions: This analysis demonstrated a positive benefit-risk profile with rivaroxaban versus trial comparators in older patients with NVAF or VTE, with benefit-risk increasingly favoring rivaroxaban with increasing age.

Clinical trial registration: http://ClinicalTrials.gov , identifiers: NCT00403767 (ROCKET-AF), NCT00440193 (EINSTEIN DVT), NCT00439777 (EINSTEIN PE), NCT00439725 (EINSTEIN Extension), and NCT02064439 (EINSTEIN CHOICE).