Antithrombotic prophylaxis with rivaroxaban in patients with prehospital COVID-19: A meta-analysis of two placebo-controlled trials.

Background We conducted a prespecified meta-analysis of two randomized, placebo-controlled trials of rivaroxaban 10 mg daily in prehospital patients with acute COVID-19. Individually, the trials had limited power to detect a treatment effect due to recruitment stopping ahead of plan. Methods The statistical analysis plan for the meta-analysis was finalized before unblinding of PREVENT-HD, the larger of the two trials. Pooled risk ratios and pooled risk differences along with the 2-sided 95% confidence intervals were calculated using random-effect models. Findings Rivaroxaban did not reduce the occurrence of either the primary prespecified endpoint, a composite of symptomatic arterial and venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, all-cause hospitalization and all-cause mortality (risk difference 0.0044, 95% confidence interval -0.0263, 0.0175; p=0.69 for pooled risk difference) or the secondary endpoint of all-cause hospitalization (p=0.76). Although thrombotic events were infrequent, pooled analysis did reveal that rivaroxaban reduced arterial and venous thrombotic events (placebo 6 events, rivaroxaban 0 events; pooled risk difference -0.0068, 95% confidence interval -0.0132, -0.0006; p=0.03). In the pooled studies, only one major bleeding event was observed in a rivaroxaban-allocated patient with no critical site or fatal bleeding events. Interpretation Although this meta-analysis does not support antithrombotic prophylaxis with rivaroxaban in a broad prehospital population with acute COVID-19, the prevention of arterial and venous thrombotic events among rivaroxaban-allocated patients is consistent with the known thromboprophylactic effect of the drug in medically ill patients.