Effectiveness of oral antiviral agents on long-term cardiovascular risk in nonhospitalized patients with COVID-19: A multicenter matched cohort study

Abstract

Although a novel oral antiviral agent can improve short-term COVID-19 outcomes, its effects on the long-term outcomes, namely the risk of major adverse cardiovascular events (MACEs), remains unknown. This retrospective cohort study used the TriNetX research network to identify nonhospitalized adult patients with COVID-19 between March 1, 2020, and January 1, 2022. A propensity score matching method was used to form two matched cohorts with and without receiving nirmatrelvir–ritonavir (NMV-r) or molnupiravir. The primary outcome was the incidence of MACEs within a 30-day to 1-year period following a diagnosis of COVID-19. Two cohorts of each 80 888 patients with balanced baseline characteristics were formed using propensity score matching. During the follow-up period, 976 patients in the study group and 1609 patients in the control group developed MACE. Overall, the study group had a significantly lower risk of MACE than the control group (hazard ratio [HR], 0.683; 95% confidence interval: 0.630–0.739). The significantly lower HRs of overall MACEs were consistently observed in most subgroup analyses (age: >41–≤64 years: 0.60 [0.52–0.89]; age: ≥65 years: 0.68 [0.62–0.76]; women: 0.63 [0.57–0.71]; men: 0.62 [0.55–0.70]; vaccinated: 0.74 [0.63–0.88]; unvaccinated: 0.66 [0.60–0.73]; NMV-r; 0.65 [0.59–0.71]; and molnupiravir: 0.75 [0.61–0.92]). In conclusion, novel oral antiviral agents, namely NMV-r and molnupiravir, were effective in reducing long-term MACEs among nonhospitalized patients with COVID-19, particularly when treated with NMV-r or in patients aged ≥40 years. These findings suggest the potential role of novel antiviral agents as a preventive measure to reduce further adverse cardiovascular outcomes.