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Rivaroxaban for Prevention of Thrombotic Events for Outpatients With COVID-19
Quick Takes
- Amiodarone has important drug-drug interactions with the oral factor Xa inhibitors apixaban and rivaroxaban.
- Concurrent use of amiodarone and apixaban/rivaroxaban was associated with higher rates of bleeding hospitalization than with flecainide or sotalol.
- Rates of bleeding were higher among rivaroxaban users than apixaban users who also used amiodarone as compared to flecainide or sotalol.
Study Questions:
Does prophylaxis with rivaroxaban safely reduce the frequency of venous and arterial thrombosis, hospitalization, and death in nonhospitalized patients with symptomatic coronavirus disease 2019 (COVID-19) and at least one thrombosis risk factor?
Methods:
The PREVENT-HD trial authors conducted a randomized clinical trial between August 2020 and April 2022 at 14 US integrated health care delivery centers. Adult patients were eligible for enrollment if they had symptomatic COVID-19 infection, were not hospitalized, but had one or more thrombosis risk factors (increased D-dimer; documented thrombophilia; prior venous thromboembolism [VTE]; history of cancer, coronary artery disease, peripheral artery disease, cerebrovascular disease, or ischemic stroke). Patients were excluded if the COVID-19 test was >2 weeks old. Patients were randomized to receive rivaroxaban 10 mg daily or placebo for 35 days. The primary efficacy outcome was time to first occurrence of a composite of symptomatic VTE, myocardial infarction, ischemic stroke, acute limb ischemia, systemic arterial embolism, hospitalization, or death through day 35. The primary safety endpoint was International Society on Thrombosis and Hemostasis-defined critical-site or fatal bleeding. The study was stopped prior to reaching target event-driven enrollment due to enrollment challenges and lower-than-expected event rates in blinded pooled analysis.
Results:
PREVENT-HD enrolled 1,284 patients through May 2022 without any loss to follow-up. The primary efficacy outcome occurred in 22/641 (3.4%) patients randomized to rivaroxaban and 19/643 (3.0%) patients randomized to placebo (hazard ratio, 1.16; 95% confidence interval, 0.63-2.15; p = 0.63). No patient in either group experienced a critical-site or fatal bleeding event.
Conclusions:
The authors concluded that given the limitation of an underpowered study, rivaroxaban prophylaxis did not reduce a composite of venous and arterial thrombotic events, hospitalization, or death among ambulatory patients with symptomatic COVID-19 infection.
Perspective:
Early in the COVID-19 pandemic, reported rates of thromboembolism were extremely high in hospitalized patients. This led to several randomized trials demonstrating benefit for chemoprophylaxis in the hospitalized patients, at various levels of anticoagulant intensity. Subsequent trials of nonhospitalized patients with COVID-19 infection have not found benefit with the use of various chemoprophylaxis regimens, including apixaban or aspirin. The PREVENT-HD study similarly found no statistically significant benefit to outpatient thromboprophylaxis with rivaroxaban in patients with nonhospitalized COVID-19 infection. Despite being terminated prematurely and enrolling a higher-risk population, the results of this study largely align with those of prior trials and observational data suggesting a low rate of thromboembolism among patients with COVID-19 infection who do not require hospitalization.
Clinical Topics: Anticoagulation Management, COVID-19 Hub, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD)
Keywords: Anticoagulants, Coronary Artery Disease, COVID-19, Embolism, Hemorrhage, Hemostasis, Ischemic Stroke, Myocardial Infarction, Outpatients, Peripheral Arterial Disease, Primary Prevention, Risk Factors, Rivaroxaban, Thrombophilia, Thrombosis, Vascular Diseases, Venous Thrombosis
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