Prophylactic effect of ursodeoxycholic acid on reducing complications of cardiac surgery in patients with previous COVID-19 infection: a randomized clinical trial

Background: Patients with coronavirus disease 2019 (COVID-19) infection prior to cardiac surgery are at a higher risk of contracting the virus and worse outcomes. Administration of ursodeoxycholic acid (UDCA) may be effective in reducing the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, it remains unclear whether prophylactic use of UDCA could prevent complications in cardiac surgical patients with previous COVID-19 infection. Methods: In one comparison from a 2 × 2 factorial trial, we randomly assigned patients with COVID-19 infection prior to cardiac surgery to UDCA or control in a 1:1 ratio. The randomization process was initiated 2 days before surgery by a central randomization system. The participants in the UDCA group received UDCA (15 mg/kg of body weight) on the day of randomization, administered orally twice a day during breakfast and dinner for 5 days. The primary outcome was a composite endpoint of all-cause death, myocardial infarction, stroke, moderate or severe acute kidney injury, and COVID-19 pneumonia within 30 days after surgery. Results: From January 2023 through March 2023, a total of 500 participants were randomized, and all the participants (UDCA: 250 and control: 250; mean [standard deviation] age, 57.1 [11.5] years; 25.4% female) were included in the primary analysis. The primary outcome event occurred in 37 (14.8%) participants in the UDCA group and 35 (14.0%) participants in the control group (risk difference, 0.8% [97.5% confidence interval [CI], − 6.2% to 7.8%]; risk ratio, 1.08 [97.5% CI, 0.63 to 1.85]). The results were consistent in subgroups. Additionally, the incidence of COVID-19 pneumonia within 30 days was similar between the UDCA group and the control group (10.4% vs. 7.6%; risk difference, 2.8 [95% CI −2.2 to 7.8]; risk ratio, 1.35 [95% CI 0.75 to 2.44]). Serious adverse events occurred in 94 (37.6%) participants in the UDCA group and 94 (37.6%) participants in the control group (P>0.05). There were also no significant between-group differences in the incidence of the other secondary outcomes. Conclusion: Among patients who underwent cardiac surgery following a recent COVID-19 infection, prophylactic use of UDCA for a 5-day course was not associated with better postoperative outcomes, including major complications and COVID-19 reinfection.