Rivaroxaban Noninferior to Enoxaparin for Bleeding in Acute Coronary Syndrome

Short-term oral 5-mg rivaroxaban is noninferior to subcutaneous enoxaparin (1 mg/kg) for reducing risk for major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) treated with dual antiplatelet therapy (DAPT) who miss the primary reperfusion window, according to findings published in the Journal of the American Medical Association Network Open.

Researchers sought to compare the efficacy and safety of low-dose rivaroxaban vs enoxaparin in the acute phase of ACS in an open-label, prospective, multicenter noninferiority trail (ClinicalTrials.gov Identifier: NCT03363035). The primary efficacy endpoint was a combination of stroke, revascularization, myocardial infarction, or cardiac death (MACEs) during the 6-month follow-up. The primary safety endpoint was bleeding events.

The study took place January 2017 through May 2021, at 21 hospitals in China. Patients were at least 18 years of age, had been diagnosed with ACS, had ST-segment elevation myocardial infarction (STEMI) and missed the recommended time window for revascularization, had non-ST-segment elevation ACS without an indication for primary percutaneous coronary intervention and were waiting for selective revascularization, or had indication for short-term use of enoxaparin combined with DAPT.

Participants were randomly assigned in a 1:1:1 ratio to receive DAPT plus oral rivaroxaban 2.5 mg, rivaroxaban 5 mg, or subcutaneous enoxaparin 1 mg/kg twice daily for 3.7 mean days. Patients with contraindications for rivaroxaban or enoxaparin, who already received thrombolytic therapy or revascularization, who had revascularization therapy planned within 12 hours, and patients enrolled in another clinical study were excluded.

A total of 2046 patients completed the trial. Participants (mean age 65.8 [SD, 8.2] years; 29.5% women) were randomized to rivaroxaban 2.5-mg (n=683), rivaroxaban 5-mg (n=683), or enoxaparin 1-mg/kg (n=680). Baseline characteristics were similar among all groups. There were 71.1% of patients who received reperfusion therapy before discharge for the index diagnosis.

There were 32 bleeding events in the rivaroxaban 2.5-mg group, 36 in the rivaroxaban 5-mg group, and 46 in the enoxaparin group.

There was a similar incidence of MACE among all groups. Noninferiority for the primary efficacy endpoints was not reached in the rivaroxaban 2.5-mg group (hazard ratio [HR], 0.68; 95% CI, 0.36-1.30; P =.05) compared with the enoxaparin group. Noninferiority for the primary efficacy endpoints was reached in the rivaroxaban 5-mg group (HR, 0.60; 95% CI, 0.31-1.16, P =.02) compared with the enoxaparin group.

Some study limitations include the lack of generalizability and an underpowered sample size. Additionally, there was only a 6 month follow-up window.

“The data obtained from this small trial might be helpful for designing future noninferiority trials with sufficient sample sizes to test whether rivaroxaban 5 mg twice daily plus DAPT might be a reasonable alternative regimen to enoxaparin plus DAPT during the acute phase of ACS for patients who missed the primary reperfusion window or not,” the study authors wrote.