Navarese EP, Podhajski P, Andreotti F, La Torre G, Gajda R, Radziwanowski A, Nowicka M, Bukowski P, Gajda J, Omyła M, Lackowski P, Piasecki M, Jasiewicz M, Szymański P, Pietrzykowski Ł, Michalski P, Kubica A, Urbanowicz I, Orsini N, Conte M, Pinkas J, Brouwer MA, Kubica J
Cardiol J - (-) - [2022-08-01; online 2022-08-01]
Ion channel inhibition may offer protection against coronavirus disease 2019 (COVID-19). Inflammation and reduced platelet count occur during COVID-19 but precise quantification of risk thresholds is unclear. The Recovery-SIRIO study aimed to assess clinical effects of amiodarone and verapamil and to relate patient phenotypes to outcomes. RECOVERY-SIRIO is a multicenter open-label 1:1:1 investigator-initiated randomized trial with blinded event adjudication. A sample of 804 symptomatic hospitalized nonintensive-care COVID-19 patients, follow-up for 28 days was initially planned. The trial was stopped when a total of 215 patients had been randomized to amiodarone (n = 71), verapamil (n = 72) or standard care alone (n = 72). At 15 days, the hazard ratio (hazard ratio [HR], 95% confidence interval [CI]) for clinical improvement was 0.77 (0.52-1.14) with amiodarone and 0.97 (0.81-1.17) with verapamil as compared to usual care. Clinically relevant associations were found between mortality or lack of clinical improvement and higher peak C-reactive protein (CRP) levels or nadir platelet count at 7, 10 and 15 days. Mortality rate increased by 73% every 5 mg/dL increment in peak CRP (HR 1.73, 95% CI 1.27-2.37) and was two-fold higher for every decrement of 100 units in nadir platelet count (HR 2.19, 95% CI 1.37-3.51). By cluster analysis, thresholds of 5 mg/dL for peak CRP and 187 ×10³/mcL for nadir platelet count identified the phenogroup at greatest risk of dying. In this randomized trial, neither amiodarone nor verapamil were found to significantly accelerate short-term clinical improvement. Peak CRP and nadir platelet counts were associated with increased mortality both in isolation and by cluster analysis.