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

Hakeam A Hakeam, Muhannad Alsemari, Zainab Al Duhailib, Leen Ghonem, Saad A Alharbi, Eid Almutairy, Nader M Bin Sheraim, Meshal Alsalhi, Ali Alhijji, Sara AlQahtani, Mohammed Khalid, Mazin Barry, Hakeam A Hakeam, Muhannad Alsemari, Zainab Al Duhailib, Leen Ghonem, Saad A Alharbi, Eid Almutairy, Nader M Bin Sheraim, Meshal Alsalhi, Ali Alhijji, Sara AlQahtani, Mohammed Khalid, Mazin Barry

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.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Kaplan-Meier cumulative probability of death among patients with COVID-19 receiving or not receiving ACE-I/ARB therapy. Adjusted multivariable Cox regression model for age, obesity and chronic illness testing the association of ACE-I/ARB use with the risk of death (HR 0.69, 95% CI 0.30-1.58; P = .35).
Figure 2.
Figure 2.
Kaplan-Meier cumulative probability of) mechanical ventilation among patients with COVID-19 receiving or not receiving ACE-I/ARB therapy. Adjusted multivariable Cox regression model for age, obesity, and chronic illness testing the association of ACE-I/ARB use and mechanical ventilation (HR 0.90, 95% CI 0.45-1.80, P = .77).

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