Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Dec 2021)

Angiotensin‐Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID‐19

  • Michael Pan,
  • Alexi Vasbinder,
  • Elizabeth Anderson,
  • Toniemarie Catalan,
  • Husam R. Shadid,
  • Hanna Berlin,
  • Kishan Padalia,
  • Patrick O’Hayer,
  • Chelsea Meloche,
  • Tariq U. Azam,
  • Ibrahim Khaleel,
  • Erinleigh Michaud,
  • Pennelope Blakely,
  • Abbas Bitar,
  • Yiyuan Huang,
  • Lili Zhao,
  • Rodica Pop‐Busui,
  • Sven H. Loosen,
  • Athanasios Chalkias,
  • Frank Tacke,
  • Evangelos J. Giamarellos‐Bourboulis,
  • Jochen Reiser,
  • Jesper Eugen‐Olsen,
  • Salim S. Hayek

DOI
https://doi.org/10.1161/JAHA.121.023535
Journal volume & issue
Vol. 10, no. 24

Abstract

Read online

Background Use of angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) is thought to affect COVID‐19 through modulating levels of angiotensin‐converting enzyme 2, the cell entry receptor for SARS‐CoV2. We sought to assess the association between ACEi/ARB, biomarkers of inflammation, and outcomes in patients hospitalized for COVID‐19. Methods and Results We leveraged the ISIC (International Study of Inflammation in COVID‐19), identified patients admitted for symptomatic COVID‐19 between February 1, 2020 and June 1, 2021 for COVID‐19, and examined the association between in‐hospital ACEi/ARB use and all‐cause death, need for ventilation, and need for dialysis. We estimated the causal effect of ACEi/ARB on the composite outcomes using marginal structural models accounting for serial blood pressure and serum creatinine measures. Of 2044 patients in ISIC, 1686 patients met inclusion criteria, of whom 398 (23.6%) patients who were previously on ACEi/ARB received at least 1 dose during their hospitalization for COVID‐19. There were 215 deaths, 407 patients requiring mechanical ventilation, and 124 patients who required dialysis during their hospitalization. Prior ACEi/ARB use was associated with lower levels of soluble urokinase plasminogen activator receptor and C‐reactive protein. In multivariable analysis, in‐hospital ACEi/ARB use was associated with a lower risk of the composite outcome of in‐hospital death, mechanical ventilation, or dialysis (adjusted hazard ratio 0.49, 95% CI [0.36–0.65]). Conclusions In patients hospitalized for COVID‐19, ACEi/ARB use was associated with lower levels of inflammation and lower risk of in‐hospital outcomes. Clinical trials will define the role of ACEi/ARB in the treatment of COVID‐19. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.

Keywords