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

Abstract

ObjectiveThe 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.MethodsPubMed (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.ResultsFourteen 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.ConclusionsIn 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 numberThe present study has been registered with PROSPERO (registration ID: CRD 42020187963).

Inpatient Omission of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Is Associated With Morbidity and Mortality in Coronavirus Disease 2019

“…[6][7][8] Others concluded that prior ACEi/ARB use reduced the risk of mortality and ICU admission, and decreased length of stay. [9][10][11][12][13][14] There is theoretical basis for both deleterious and protective effects of these agents in SARS-CoV-2 infection. 22 Notably however, there is no substantial clinical evidence that ACEi/ARB use worsens outcomes in COVID-19 when compared to appropriately matched controls.…”

“…Broadly these suggest that antecedent ACEi/ARB therapy is not associated with worsened outcomes in COVID-19, and that their use might confer certain protective benefits. [6][7][8][9][10][11][12][13][14] The impact of ACEi/ARB provision during acute COVID-19 illness has been inadequately examined. To date few studies have attempted to address this question.…”

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Hypertension and COVID-19: Ongoing Controversies

“…There was a long discussion regarding the impact of antihypertensive therapy in COVID-19 patients and particularly of angiotensin-converting enzyme inhibitors (ACEI) and blockers of angiotensin I receptors (ARB). After initial reports that showed higher prevalence of use of these medications in COVID-19 patients with cardiac injury and more severe course of disease ( 8 , 9 ), numerous original studies and meta-analysis reported no relationship with severity or mortality in COVID-19 patients ( 10 , 11 ) or even benefit of taking renin-angiotensin-aldosterone inhibitors in COVID-19 patients ( 12 , 13 ).…”