Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Blockers With Severity of COVID-19: A Multicenter, Prospective Study

J Cardiovasc Pharmacol Ther. 2021 May;26(3):244-252. doi: 10.1177/1074248420976279. Epub 2020 Nov 24.

Abstract

Background: Speculations whether treatment with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) predisposes to severe coronavirus disease 2019 (COVID-19) or worsens its outcomes. This study assessed the association of ACE-I/ARB therapy with the development of severe COVID-19.

Methods: This multi-center, prospective study enrolled patients hospitalized for COVID-19 and receiving one or more antihypertensive agents to manage either hypertension or cardiovascular disease. ACE-I/ARB therapy associations with severe COVID-19 on the day of hospitalization, intensive care unit (ICU) admission, mechanical ventilation and in-hospital death on follow-up were tested using a multivariate logistic regression model adjusted for age, obesity, and chronic illnesses. The composite outcome of mechanical ventilation and death was examined using the adjusted Cox multivariate regression model.

Results: Of 338 enrolled patients, 245 (72.4%) were using ACE-I/ARB on the day of hospital admission, and 197 continued ACE-I/ARB therapy during hospitalization. Ninety-eight (29%) patients had a severe COVID-19, which was not significantly associated with the use of ACE-I/ARB (OR 1.17, 95% CI 0.66-2.09; P = .57). Prehospitalization ACE-I/ARB therapy was not associated with ICU admission, mechanical ventilation, or in-hospital death. Continuing ACE-I/ARB therapy during hospitalization was associated with decreased mortality (OR 0.22, 95% CI 0.073-0.67; P = .008). ACE-I/ARB use was not associated with developing the composite outcome of mechanical ventilation and in-hospital death (HR 0.95, 95% CI 0.51-1.78; P = .87) versus not using ACE-I/ARB.

Conclusion: Patients with hypertension or cardiovascular diseases receiving ACE-I/ARB therapy are not at increased risk for severe COVID-19 on admission to the hospital. ICU admission, mechanical ventilation, and mortality are not associated with ACE-I/ARB therapy. Maintaining ACE-I/ARB therapy during hospitalization for COVID-19 lowers the likelihood of death.

Clinical trial registration: ClinicalTrials.gov, NCT4357535.

Trial registration: ClinicalTrials.gov NCT04357535 NCT04357535.

Keywords: COVID-19; SARS-CoV-2; angiotensin II receptor blockers; angiotensin-converting enzyme inhibitor.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • C-Reactive Protein / biosynthesis
  • COVID-19 / epidemiology*
  • COVID-19 / mortality
  • COVID-19 / physiopathology*
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / epidemiology*
  • Female
  • Hematologic Tests
  • Hospital Mortality
  • Humans
  • Hypertension / drug therapy
  • Hypertension / epidemiology
  • Intensive Care Units / statistics & numerical data
  • Logistic Models
  • Male
  • Middle Aged
  • Obesity / epidemiology
  • Prospective Studies
  • Respiration, Artificial / statistics & numerical data
  • SARS-CoV-2
  • Severity of Illness Index

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT04357535
  • ClinicalTrials.gov/NCT04357535