Rivaroxaban in Patients With a Recent Acute Coronary Syndrome

Study Questions:

What is the effect of low-dose rivaroxaban on cardiovascular outcomes in patients with a recent acute coronary syndrome (ACS)?

Methods:

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 51) was a double-blind, placebo-controlled trial. The investigators randomly assigned 15,526 patients with a recent ACS to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy endpoint was a composite of death from cardiovascular causes, myocardial infarction, or stroke. The authors used hazard ratios and two-sided 95% confidence intervals to compare the study groups.

Results:

Rivaroxaban significantly reduced the primary efficacy endpoint, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74-0.96; p = 0.008), with significant improvement for both the twice-daily 2.5 mg dose (9.1% vs. 10.7%, p = 0.02) and the twice-daily 5 mg dose (8.8% vs. 10.7%, p = 0.03). The twice-daily 2.5 mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, p = 0.002) and from any cause (2.9% vs. 4.5%, p = 0.002), a survival benefit that was not seen with the twice-daily 5 mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary artery bypass grafting (2.1% vs. 0.6%, p < 0.001) and intracranial hemorrhage (0.6% vs. 0.2%, p = 0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, p = 0.66) or other adverse events. The twice-daily 2.5 mg dose resulted in fewer fatal bleeding events than the twice-daily 5 mg dose (0.1% vs. 0.4%, p = 0.04).

Conclusions:

The authors concluded that in patients with a recent ACS, rivaroxaban reduced the risk of the composite endpoint of death from cardiovascular causes, myocardial infarction, or stroke.

Perspective:

This study reports that rivaroxaban significantly reduced the primary efficacy endpoint of death from cardiovascular causes, myocardial infarction, or stroke in patients with ACS. In terms of safety, the two doses of rivaroxaban increased the rates of major bleeding and intracranial hemorrhage, as compared with placebo, without a significant increase in fatal bleeding. Furthermore, the lower dose of rivaroxaban resulted in less bleeding than the higher dose. The addition of very-low-dose anticoagulation with rivaroxaban may represent a new treatment strategy in patients with a recent ACS, but additional studies are needed to balance ischemic versus bleeding risks when selecting the type, number, and duration of antithrombotic therapies for individual patients.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Anticoagulation Management and ACS, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Intracranial Hemorrhages, Morpholines, Coronary Angiography, Thiophenes, Heparin, Low-Molecular-Weight, Cardiovascular Diseases, Confidence Intervals, Coronary Artery Bypass


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