Antithrombotic Prophylaxis with Rivaroxaban in Patients with Prehospital COVID-19: A Meta-analysis of Two Placebo-Controlled Trials

Abstract

Background We conducted a prespecified meta-analysis of two randomized, placebo-controlled trials of rivaroxaban 10 mg daily in prehospital patients with acute coronavirus disease 2019 (COVID-19). Individually, the trials had limited power to detect a treatment effect due to recruitment stopping ahead of plan.

Material and 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 two-sided 95% confidence intervals were calculated using random-effect models.

Results 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.

Conclusion 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.

Keywords

COVID-19 - clinical trial - direct thrombin agent - meta-analysis

Publikationsverlauf

Eingereicht: 23. September 2023

Angenommen: 21. November 2023

Accepted Manuscript online:
23. November 2023

Artikel online veröffentlicht:
21. Dezember 2023

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