Renin-angiotensin-aldosterone system inhibitors and the risk of mortality in patients with hypertension hospitalised for COVID-19: systematic review and meta-analysis

Open Heart. 2020 Nov;7(2):e001353. doi: 10.1136/openhrt-2020-001353.

Abstract

Objective: The association between the use of renin-angiotensin-aldosterone (RAAS) inhibitors and the risk of mortality from COVID-19 is unclear. We aimed to estimate the association of RAAS inhibitors, including ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality risk in patients with hypertension.

Methods: PubMed (MEDLINE) SCOPUS, OVID, Cochrane Library databases and medrxiv.org were searched from 1 January 2020 to 1 September 2020. Studies reporting the association of RAAS inhibitors (ACEi or ARBs) and mortality in patients with hypertension, hospitalised for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio (RR) estimates, and heterogeneity was quantified.

Results: Fourteen studies were included in the systematic review (n=73,073 patients with COVID-19; mean age 61 years; 53% male). Overall, the between-study heterogeneity was high (I2=80%, p<0.01). Patients with hypertension with prior use of RAAS inhibitors were 35% less likely to die from COVID-19 compared with patients with hypertension not taking RAAS inhibitors (pooled RR 0.65, 95% CI 0.45 to 0.94). The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations was graded as 'moderate' quality.

Conclusions: In this meta-analysis, with prior use of RAAS inhibitors was associated with lower risk mortality from COVID-19 in patients with hypertension. Our findings suggest a potential protective effect of RAAS-inhibitors in COVID-19 patients with hypertension.

Prospero registration number: The present study has been registered with PROSPERO (registration ID: CRD 42020187963).

Keywords: antihypertensive drugs; hypertension; meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • COVID-19
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / mortality*
  • Coronavirus Infections / therapy
  • Female
  • Hospitalization*
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / mortality
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / mortality*
  • Pneumonia, Viral / therapy
  • Protective Factors
  • Renin-Angiotensin System / drug effects*
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

Substances

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