Compared with placebo, administration of the direct-acting oral anticoagulant (DOAC) for 35 days in non-hospitalized patients with symptomatic COVID-19 who had at least one risk factor for thrombosis did not reduce thromboembolic events or hospitalization or the death of all causes. the primary intention-to-treat analysis. The rate was 3.4% with rivaroxaban versus 3.0% with placebo, based on 22 and 19 events, respectively, among more than 1,200 trial participants (HR 1.16, 95% CI 0.63–2, 15), Gregory Piazza, MD, Brigham and Women’s Hospital and Harvard Medical School in Boston, reported at the American Heart Association meeting in Chicago. “With the caveat that the trial was unable to provide a definitive conclusion, these data do not support routine antithrombotic prophylaxis in non-hospitalized patients with symptomatic COVID-19,” he told attendees, noting that the trial was stopped early at about 1 – the third of the planned registrations due to the reduction in the number of the pandemic and the severity. That’s a message that parallels other trials of anticoagulants in outpatient care for COVID-19, noted Renato Lopes MD, PhD, of the Duke Clinical Research Institute in Durham, North Carolina, who served as a study panelist at the clinic’s final session. test. Meta-analysis with the almost universally negative trials that have emerged so far suggested no benefit (OR 0.93, 95% CI 0.70-1.23) for the primary endpoint, although it varied between trials or for mortality (OR 0.64, 95% CI 0.25-1.61). “The results of this trial, in light of the body of evidence in this area, do not support the routine use of any antithrombotic therapy for outpatients with COVID-19,” Lopez said. PREVENT randomized 1,284 symptomatic patients with a positive laboratory antigen or PCR assay for SARS-CoV-2 recruited through US integrated health networks to rivaroxaban (10 mg) or placebo once daily, stratified by number of days from positive test to randomization. Participants were followed for outcomes without laboratory or office visits, using electronic case report forms and electronic medical records collected only through telemedicine or home visits. Patients were not enrolled if the original plan of care included hospitalization. Enrollment criteria were also selected for a higher thrombotic risk group by requiring at least one of the following risk factors:
Age ≥ 60 years Previous history of venous thromboembolism (VTE), thrombophilia, coronary or peripheral artery disease, cardiovascular disease or stroke, cancer, diabetes requiring medication, or heart failure BMI ≥35 kg/m2 Elevated D-dimer
The most common risk factors were older age, obesity and diabetes. About a quarter of the participants had at least two risk factors. The average age was 56 years. nearly 30% of participants were non-white and approximately 60% were female. The primary efficacy endpoint was the first occurrence of a composite of symptomatic VTE, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system embolism, all-cause hospitalization, and all-cause mortality by day 35. For this endpoint, the modified intention-to-treat analysis yielded a change in direction compared with the intention-to-treat analysis, although not statistically significant, of 2.0% with rivaroxaban versus 2.7% with placebo (HR 0.75, 95 % CI 0.35-1.58). Piazza argued that up to more hospitalizations before receiving the study drug in the rivaroxaban group, while Lopes suggested that the difference merits further investigation. The first important secondary outcome of the composite of symptomatic VTE, arterial thrombotic events and all-cause mortality similarly showed no significant difference. A post hoc exploratory analysis suggested fewer combined symptomatic VTE and arterial thrombotic events, particularly ischemic stroke, but Lopes urged caution with such unspecified analyses. In terms of safety, there were no fatal or critical site bleeds in the trial and a “significant but modest” increase in non-clinically relevant bleeds with rivaroxaban versus placebo. “We have seen an explosion of observational data early in the pandemic suggesting that patients with COVID-19 may benefit from a more intense form of anticoagulation. However, we have also learned to be cautious about observational data when discussing treatment outcomes.” , Lopez noted. . That the findings were the opposite of what might have been initially assumed in the pandemic, he said, “demonstrates once again why we need randomized trials, as they are the only reliable way to guide medical decisions in clinical practice.” Revelations The trial was funded by Janssen. Piazza disclosed research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific as well as consulting fees from Bristol-Myers Squibb/Pfizer Alliance, Boston Scientific, Janssen, NAMSA, Prairie Education and Research Cooperative, Boston Clinical Research Institute and Amgen. Lopez disclosed relationships with Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis, Bayer, Novo Nordisk, and Boehringer Ingelheim.
