Dataset Information

Renin-angiotensin-system inhibitors and all-cause mortality in patients with COVID-19: a systematic review and meta-analysis of observational studies.

ABSTRACT:

Aims

We sought to evaluate the association of angiotensin-converting-enzyme inhibitors (ACEI) or AT1 blockers (ARB) therapy with clinical outcomes in patients with coronavirus disease 2019 (COVID-19).

Methods and results

Electronic databases were searched to identify published studies that reported clinical outcomes in patients with COVID-19 who were or were not taking an ACEI/ARB. We studied all-cause mortality and/or severe disease outcomes. Fully adjusted effect estimates from individual studies were pooled using a random-effects model. In total, 34 (31 cohort-based and three case-control) studies met our eligibility criteria. Due to the inherent differences between cohort and case-control studies, we did not combine results of these studies but used them to identify the consistency of their results. The 31 cohort studies provided outcome data for 87 951 patients with COVID-19, of whom 22 383/83 963 (26.7%) were on ACEI/ARB therapy. In pooled analysis, we found no association between the use of ACEI/ARB and all-cause mortality/severe disease [relative risk: 0.94, 95% confidence interval (CI): 0.86-1.03, I2 = 57%, P = 0.20] or occurrence of severe disease (relative risk: 0.93, 95% CI: 0.74-1.17, I2 = 56%, P = 0.55). Analysis of three population-based case-control studies identified no significant association between ACEI/ARB (pooled odds ratio: 1.00, 95% CI: 0.81-1.23, I2 = 0, P = 0.98) and all-cause mortality/severe disease. In 13 of the 31 cohort studies as well as in three case-control studies that reported outcomes separately for ACEI and ARB, there was no differential effect for mortality/severe disease outcomes.

Conclusion

In patients with COVID-19, we found no association between ACEI/ARB treatment and mortality/severe disease. ACEI/ARB should not be discontinued, unless clinically indicated.

SUBMITTER: Bavishi C

PROVIDER: S-EPMC8362761 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Renin-angiotensin aldosterone system (RAAS) inhibitor-COVID-19 studies, observational in design, appear to use biased methods that can distort the interaction between RAAS inhibitor use and COVID-19 risk. This study assessed the extent of bias in that research and reevaluated RAAS inhibitor-COVID-19 associations in studies without critical risk of bias. Methods and Results Searches were performed in MEDLINE, EMBASE, and CINAHL databases (December 1, 2019 to October 21, 2021) identifying studies that compared the risk of infection and/or severe COVID-19 outcomes between those using or not using RAAS inhibitors (ie, angiotensin-converting enzyme inhibitors or angiotensin II type-I receptor blockers). Weighted hazard ratios (HR) and 95% CIs were extracted and pooled in fixed-effects meta-analyses, only from studies without critical risk of bias that assessed severe COVID-19 outcomes. Of 169 relevant studies, 164 had critical risks of bias and were excluded. Ultimately, only two studies presented data relevant to the meta-analysis. In 1 351 633 people with uncomplicated hypertension using a RAAS inhibitor, calcium channel blocker, or thiazide diuretic in monotherapy, the risk of hospitalization (angiotensin-converting enzyme inhibitor: HR, 0.76; 95% CI, 0.66-0.87; P<0.001; angiotensin II type-I receptor blockers: HR, 0.86; 95% CI, 0.77-0.97; P=0.015) and intubation or death (angiotensin-converting enzyme inhibitor: HR, 0.64; 95% CI, 0.48-0.85; P=0.002; angiotensin II type-I receptor blockers: HR, 0.74; 95% CI, 0.58-0.95; P=0.019) with COVID-19 was lower in those using a RAAS inhibitor. However, these protective effects are probably not clinically relevant. Conclusions This study reveals the critical risk of bias that exists across almost an entire body of COVID-19 research, raising an important question: Were research methods and/or peer-review processes temporarily weakened during the surge of COVID-19 research or is this lack of rigor a systemic problem that also exists outside pandemic-based research? Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021237859.