Article Text

Original research
Renin–angiotensin–aldosterone system inhibitors and the risk of mortality in patients with hypertension hospitalised for COVID-19: systematic review and meta-analysis
  1. Anna E Ssentongo1,2,
  2. Paddy Ssentongo2,3,4,
  3. Emily S Heilbrunn2,
  4. Alain Lekoubou2,
  5. Ping Du2,
  6. Duanping Liao2,
  7. John S Oh1 and
  8. Vernon M Chinchilli2
  1. 1Department of Surgery, Penn State College of Medicine, Hershey, Pennsylvania, USA
  2. 2Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania, USA
  3. 3Center for Neural Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA
  4. 4Department of Engineering, Science and Mechanics, The Pennsylvania State University, University Park, Pennsylvania, USA
  1. Correspondence to Dr Anna E Ssentongo; assentongo{at}


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 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).

  • hypertension
  • antihypertensive drugs
  • meta-analysis

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  • AES, PS and ESH contributed equally.

  • Contributors AES, PS, ESH and VMC conceived the study. AES, ESH and PS conducted the literature search. AES and PS completed data analysis. AES, DL, PD, VMC, AL, JSO, ESH and PS interpreted the data. AES, ESH and PS wrote the manuscript. All authors agreed to the manuscript in its final form.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This is a systematic review and meta-analysis and individual patient was not used. Therefore we did not need IRB or an ethics board approval.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplemental information.