Latest COVID-19 research on VTE risk, treatment with metformin, ivermectin, fluvoxamine

Mild COVID-19 was associated with increased risk of venous thromboembolism (VTE), but the relationship was attenuated by vaccination, according to a study published by JAMA Internal Medicine on Aug. 18. The retrospective study included 18,818 outpatients with COVID-19 and 93,179 matched uninfected patients. Incidence of VTE within 30 days was 50.99 per 1,000 person-years in the COVID-19 patients compared to 2.37 per 1,000 person-years in the matched patients (hazard ratio [HR], 21.42; 95% CI, 12.63 to 36.31). However, the VTE risk was substantially attenuated with vaccination against COVID-19 (HR, 5.95; 95% CI, 1.82 to 19.5). Older age, male sex, obesity, and inherited thrombophilia all significantly increased risk for VTE in COVID-19 patients, the study found. Previous research has shown mixed results on whether COVID-19 outpatients have increased VTE risk, the authors noted. “These findings may reinforce the need for vaccination, inform VTE risk stratification, and call for targeted VTE prophylaxis strategies for unvaccinated outpatients with COVID-19,” said the authors, who added that this benefit of vaccination should be mentioned in efforts to increase uptake and that the case for testing some patients for inherited thrombophilias might be supported by these results.

COVID-19 outcomes are not improved by early treatment with metformin, ivermectin, or fluvoxamine, according to a trial published by the New England Journal of Medicine on Aug. 17.

The phase 3 trial used a 2-by-3 factorial design to test the effectiveness of the three drugs in preventing serious infection in outpatients. The 1,323 patients were overweight or obese, between the ages of 30 and 85 years, and enrolled within seven days of symptom onset; 52% had been vaccinated. The primary composite end point was hypoxemia, ED visit, hospitalization, or death (adjusted odds ratios versus placebo, 0.84 [95% CI, 0.66 to 1.09] with metformin, 1.05 [95% CI, 0.76 to 1.45] with ivermectin, and 0.94 [95% CI, 0.66 to 1.36] with fluvoxamine). Prespecified secondary analyses showed only one potentially significant effect: The adjusted odds ratio for ED visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin versus placebo. However, the authors noted that “this finding was a prespecified secondary end point and thus cannot be considered to be definitive pending the results of other trials.” They concluded that none of the three drugs “resulted in a lower severity of symptoms than identically matched placebo.”

A new study provided additional data about the cardiovascular safety of the mRNA vaccines. The analysis, published by Annals of Internal Medicine on Aug. 23, used the French National Health Data System and COVID-19 vaccine databases to compare hospitalizations for myocardial infarction (MI), pulmonary embolism (PE), or stroke in 18- to 74-year-olds within three weeks of a first or second dose of the Pfizer-BioNTech, Moderna, Janssen, or Oxford-AstraZeneca vaccines versus in other periods. Neither mRNA vaccine showed any association with the studied cardiovascular events, but the first dose of the Oxford-AstraZeneca vaccine was associated with MI and PE, and an association between the Janssen vaccine and MI could not be ruled out. The results of what the authors called “the most complete study on cardiovascular adverse effects of the COVID-19 vaccines to date” are “reassuring overall,” they said. However, the evidence of possible increased cardiovascular risk after vaccination with the adenovirus vaccines should be investigated by other studies, the authors recommended.

Finally, the NIH recently updated its treatment guidelines for COVID-19. New information relevant to outpatient care includes discussion of tixagevimab plus cilgavimab (Evusheld) as pre-exposure prophylaxis in high-risk patients and reports of viral rebound, with or without recurrence of symptoms, after a course of ritonavir-boosted nirmatrelvir (Paxlovid). Several sections on clinical management of children with COVID-19 have also been added.