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CC BY-NC-ND 4.0 · Thromb Haemost
DOI: 10.1055/a-2216-5848
Blood Cells, Inflammation and Infection

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

Judith Hsia 
1   Colorado Prevention Center and Department of Medicine, University of Colorado, Aurora, Colorado, United States
,
Alex C. Spyropoulos 
2   Feinstein Institutes for Medical Research and Department of Medicine, Northwell Health, New York, New York, United States
,
Gregory Piazza
3   Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
,
Stephen Weng
4   Janssen Research and Development, Statistical Decision Sciences, Cardiovascular and Metabolism, High Wycombe, United Kingdom
,
Michael W. Dunne
5   Bill and Melinda Gates Medical Research Institute, Cambridge, Massachusetts, United States
,
Concetta Lipardi
6   Janssen Research and Development, Clinical Development, Raritan, New Jersey, United States
,
Elliot S. Barnathan 
6   Janssen Research and Development, Clinical Development, Raritan, New Jersey, United States
,
Marc P. Bonaca
1   Colorado Prevention Center and Department of Medicine, University of Colorado, Aurora, Colorado, United States
› Author Affiliations Funding The Gates MRI study was supported by grants from the Gates Philanthropy Partnerships and the Bill and Melinda Gates Foundation. PREVENT-HD was funded by the Janssen Pharmaceuticals.
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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

Supplementary Material



Publication History

Received: 23 September 2023

Accepted: 21 November 2023

Accepted Manuscript online:
23 November 2023

Article published online:
21 December 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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