Antecedent Administration of Angiotensin‐Converting Enzyme Inhibitors or Angiotensin II Receptor Antagonists and Survival After Hospitalization for COVID‐19 Syndrome

Palazzuoli, Alberto; Mancone, Massimo; De Ferrari, Gaetano M.; Forleo, Giovanni; Secco, Gioel G.; Ruocco, Gaetano M.; D'Ascenzo, Fabrizio; Monticone, Silvia; Paggi, Anita; Vicenzi, Marco; Palazzo, Anna G.; Landolina, Maurizio; Taravelli, Erika; Tavazzi, Guido; Blasi, Francesco; Infusino, Fabio; Fedele, Francesco; De Rosa, Francesco G.; Emmett, Michael; Schussler, Jeffrey M.; Tecson, Kristen M.; McCullough, Peter A.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) utilizes the angiotensin‐converting enzyme‐2 (ACE‐2) receptor to enter human cells. Angiotensin‐converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) are associated with ACE‐2 upregulation. We hypothesized that antecedent use of ACEI/ARB may be associated with mortality in coronavirus disease 2019 (COVID‐19). METHODS AND RESULTS: We used the Coracle registry, which contains data of patients hospitalized with COVID‐19 in 4 regions of Italy, and restricted analyses to those ≥50 years of age. The primary outcome was in‐hospital mortality. Among these 781 patients, 133 (17.0%) used an ARB and 171 (21.9%) used an ACEI. While neither sex nor smoking status differed by user groups, patients on ACEI/ARB were older and more likely to have hypertension, diabetes mellitus, and congestive heart failure. The overall mortality rate was 15.1% (118/781) and increased with age (P (Trend)<0.0001). The crude odds ratios (ORs) for death for ACEI users and ARB users were 0.98, 95% CI, 0.60–1.60, P=0.9333, and 1.13, 95% CI, 0.67–1.91, P=0.6385, respectively. After adjusting for age, hypertension, diabetes mellitus, and congestive heart failure, antecedent ACEI administration was associated with reduced mortality (OR, 0.55; 95% CI, 0.31–0.98, P=0.0436); a similar, but weaker trend was observed for ARB administration (OR, 0.58; 95% CI, 0.32–1.07, P=0.0796). CONCLUSIONS: In those aged ≥50 years hospitalized with COVID‐19, antecedent use of ACEI was independently associated with reduced risk of inpatient death. Our findings suggest a protective role of renin‐angiotensin‐aldosterone system inhibition in patients with high cardiovascular risk affected by COVID‐19.