Bleeding and Ischemic Events With Rivaroxaban in ACS
What is the net clinical benefit of low-dose rivaroxaban plus dual antiplatelet therapy (DAPT) vs. DAPT alone in acute coronary syndrome (ACS) when analyses are limited to fatal and irreversible bleeding and ischemic events?
The ATLAS ACS 2-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction) trial compared rivaroxaban 2.5 mg twice a day to placebo in addition to DAPT in patients with ACS. The authors compared the rate of fatal and irreversible events, including nonbleeding cardiovascular death, myocardial infarction, ischemic stroke, fatal bleeding, and intracranial bleeding.
Patients taking low-dose rivaroxaban plus DAPT experienced 115 (95% confidence interval [CI], 18-212) fewer fatal or irreversible ischemic events as compared to the placebo plus DAPT group (548 vs. 663) per 10,000 patient-years. Patients taking rivaroxaban plus DAPT experienced 10 (95% CI, -11 to +32) additional fatal or irreversible bleeding events (23 vs. 33) per 10,000 patient-years. Net clinical benefit associated with rivaroxaban therapy is estimated at 105 (95% CI, 6-204) fewer adverse fatal or irreversible events per 10,000 patient-years. Net clinical benefit continued to improve over the entire study period (up to 720 days).
The authors concluded that ACS patients treated with low-dose rivaroxaban and DAPT experience fewer severe events (fatal and irreversible) than patients treated with DAPT only.
This study challenges how we assess net clinical benefit for cardiovascular antithrombotic therapies. Rather, including some irreversible events (e.g., nonfatal myocardial infarction and nonfatal extracranial bleeding), this analysis focused on the most serious and nonirreversible outcomes. When limited to this subset of outcomes, use of rivaroxaban 2.5 mg twice a day in addition to DAPT appears favorable to DAPT alone in ACS patients. However, nonfatal bleeding events were common in the triple therapy group and remain clinically important. Nonetheless, this dose of rivaroxaban is currently not FDA approved or available in the United States, and the findings should not be extrapolated to available (higher) doses or other direct oral anticoagulants.
Keywords: Acute Coronary Syndrome, Anticoagulants, Brain Ischemia, Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Platelet Aggregation Inhibitors, Stroke, Vascular Diseases
< Back to Listings