The use of renin-angiotensin-aldosterone system (RAAS) inhibitors is associated with a lower risk of mortality in hypertensive COVID-19 patients: A systematic review and meta-analysis

J Med Virol. 2021 Mar;93(3):1370-1377. doi: 10.1002/jmv.26625. Epub 2020 Nov 10.


Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are one of the most prescribed antihypertensive medications. Previous studies showed RAAS inhibitors increase the expression of ACE2, a cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which provokes a concern that the use of ACEI and ARB in hypertensive individuals might lead to increased mortality and severity of coronavirus disease 2019 (COVID-19). To further investigate the effects of ACEI/ARB on COVID-19 patients, we systematically reviewed relevant studies that met predetermined inclusion criteria in search of PubMed, Embase, Cochrane Library databases, medRxiv, and bioRxiv. The search strategy included clinical data published through October 12, 2020. Twenty-six studies involving 8104 hypertensive patients in ACEI/ARB-treated group and 8203 hypertensive patients in non-ACEI/ARB-treated group were analyzed. Random-effects meta-analysis showed ACEI/ARB treatment was significantly associated with a lower risk of mortality in hypertensive COVID-19 patients (odds ratio [OR] = 0.624, 95% confidence interval [CI] = 0.457-0.852, p = .003, I2 = 74.3%). Meta-regression analysis showed that age, gender, study site, Newcastle-Ottawa Scale scores, comorbidities of diabetes, coronary artery disease, chronic kidney disease, or cancer has no significant modulating effect of ACEI/ARB treatment on the mortality of hypertensive COVID-19 patients (all p > .1). In addition, the ACEI/ARB treatment was associated with a lower risk of ventilatory support (OR = 0.682, 95% CI = 0.475-1.978, p = .037, I2 = 0.0%). In conclusion, these results suggest that ACEI/ARB medications should not be discontinued for hypertensive patients in the context of COVID-19 pandemic.

Keywords: ACEI/ARB; COVID-19; hypertension; mortality.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • COVID-19 / complications*
  • COVID-19 / mortality*
  • Comorbidity
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Male
  • Prognosis
  • Risk Factors


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents