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

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

Anna E Ssentongo #  1   2 , Paddy Ssentongo #  2   3   4 , Emily S Heilbrunn #  2 , Alain Lekoubou  2 , Ping Du  2 , Duanping Liao  2 , John S Oh  5 , Vernon M Chinchilli  2
Affiliations
Meta-Analysis

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

Anna E Ssentongo et al. Open Heart. 2020 Nov.

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.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
PRISMA flow diagram. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2
Pooled RR for the association of RAAS-inhibitors and COVID-19 mortality. RAAS, renin–angiotensin–aldosterone.
Figure 3
Figure 3
Pooled RR estimates of studies by covariate adjustment.
See this image and copyright information in PMC

References

    1. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271–80. 10.1016/j.cell.2020.02.052 - DOI - PMC - PubMed
    1. Guo J, Huang Z, Lin L, et al. Coronavirus disease 2019 (COVID-19) and cardiovascular disease: a viewpoint on the potential influence of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on onset and severity of severe acute respiratory syndrome coronavirus 2 infection. J Am Heart Assoc 2020;9:e016219. 10.1161/JAHA.120.016219 - DOI - PMC - PubMed
    1. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020;8:e21. 10.1016/S2213-2600(20)30116-8 - DOI - PMC - PubMed
    1. Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005;436:112–6. 10.1038/nature03712 - DOI - PMC - PubMed
    1. Tipnis SR, Hooper NM, Hyde R, et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 2000;275:33238–43. 10.1074/jbc.M002615200 - DOI - PubMed

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