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

Résumé fourni par la source

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). 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. 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). 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). Anticoagulants are medications that prevent blood clots. They can treat or prevent health problems caused by abnormal blood clotting. Anticoagulants can be used to prevent stroke in patients who have a heart condition called atrial fibrillation (AF). They can also treat or prevent blood clots that form in the veins called venous thromboembolism (VTE). As patients get older, their risk of stroke or blood clots increases. Although anticoagulants are helpful for these conditions, they can cause bleeding. The risk of bleeding increases with age and certain other diseases, such as heart failure, diabetes, and high blood pressure. When choosing an anticoagulant, it is important to look at both the benefits (reducing blood clots) and risks (bleeding) of the drug. Research studies have tested the efficacy and safety of the anticoagulant rivaroxaban by comparing it against standard treatment in patients with AF (ROCKET-AF study) and VTE (EINSTEIN studies). Our analysis used data from these studies to focus on specific outcomes related to rivaroxaban’s benefits and risks. This analysis compared the frequency of these outcomes between different treatments in all patients and in patients who were younger than 65, 65–75, and older than 75 years of age. In patients with AF or VTE, rivaroxaban had higher benefits than risks overall and for each of the age groups studied. The positive differences between benefits and risks of rivaroxaban appeared to grow in older groups of patients. These results suggest that rivaroxaban’s treatment benefits outweigh the risks in older patients.

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