Trial does not support routine antithrombotic use in ill outpatients with COVID-19
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CHICAGO — Routine antithrombotic use on top of usual care did not improve outcomes in high-risk, medically ill outpatients with SARS-CoV-2 infection vs. placebo, a speaker reported.
The results of the PREVENT-HD trial were presented at the American Heart Association Scientific Sessions.
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“Hospitalized COVID-19 patients were recommended to receive thromboprophylaxis as ‘acute, medically ill’ patients per American College of Cardiology, American College of Chest Physicians, WHO and International Society on Thrombosis and Haemostasis guidelines. Rivaroxaban was approved in the U.S. for thromboprophylaxis in hospitalized acute, medically ill patients who are at risk for venous thromboembolism but low risk for bleeding,” Gregory Piazza, MD, MS, director of the vascular medicine section of the division of cardiovascular medicine at Brigham and Women's Hospital and associate professor of medicine at Harvard Medical School, said during a presentation. “Despite focus on hospitalized patients, the majority of patients with COVID-19 were treated as outpatients.
“We hypothesized that early initiation of thromboprophylactic dosing of rivaroxaban in higher-risk outpatients with COVID-19 may lower the incidence of venous and arterial thrombotic events; reduce in situ pulmonary thrombosis and the worsening of pulmonary function that may lead to hospitalization; and reduce all-cause mortality,” Piazza said.
PREVENT-HD was a randomized, double-blind, placebo-controlled study that enrolled 1,284 medically ill outpatients with COVID-19 at 14 integrated health networks across the U.S. (mean age, 56 years; approximately 60% women; 28% from historically underrespresented groups). Adult patients with a laboratory-confirmed COVID-19 diagnosis and at least one additional risk factor were identified, contacted and enrolled in an entirely virtual manner, with no in-person visits or lab tests, and assigned to either rivaroxaban (Xarelto, Janssen/Bayer) 10 mg or placebo for 35 days on top of usual care.
The primary efficacy endpoint was time to first occurrence of a composite endpoint of symptomatic VTE, MI, stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization and all-cause mortality at 35 days. The primary safety endpoint includes time to first occurrence of International Society on Thrombosis and Hemostasis critical site and fatal bleeding on treatment.
Piazza said the PREVENT-HD trial ended enrollment early due to lower-than-expected event incidence; falling rate of SARS-CoV-2-related death and hospitalization in the U.S.; and low chances of achieving the required number of events.
In the intention-to-treat analysis, researchers observed no significant difference between rivaroxaban and placebo for the occurrence of the primary composite endpoint at 35 days (HR = 0.75; 95% CI, 0.35-1.58; P = .439); however, in a post hoc analysis, they did observe a reduced rate of symptomatic VTE and arterial thrombotic events in the rivaroxaban group (log-rank P = .025).
In addition, there were more nonmajor clinically relevant and trivial bleeds in the rivaroxaban group compared with placebo (P = .01), but events were few overall.
“Rivaroxaban, prescribed for 35 days in nonhospitalized patients with symptomatic COVID-19 at-risk for thrombosis, was not found to reduce a composite endpoint of venous and arterial thrombotic events, hospitalization and death, with the caveat that in a post hoc exploratory analysis, we observed a significant reduction in venous and arterial thrombotic events in line with the known prophylactic efficacy of rivaroxaban,” Piazza said during the presentation. “Bleeding overall was low and generally consistent with the known safety profile of rivaroxaban. With the caveat that the trial was underpowered to provide a definitive conclusion, these data do not support routine antithrombotic prophylaxis in nonhospitalized patients with symptomatic COVID-19.”
After the presentation, Renato D. Lopes, MD, MHS, PhD, professor of medicine at Duke University School of Medicine and member in the Duke Clinical Research Institute, said there should be caution when interpreting the results of the PREVENT-HD post hoc analysis.
“Of course, we would take caution with the post hoc and exploratory analysis on symptomatic VTE and arterial thrombosis, since they were not prespecified,” Lopes said. “The results of this trial, in light of the body of evidence in the field, do not support routine use of any antithrombotic therapy for outpatients with COVID-19.”
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Piazza G, et al. LBS.07: Preventing Limb Loss Through Vascular Interventions and Venous Therapies. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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