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Association of renin-angiotensin-aldosterone system inhibitors with mortality and testing positive of COVID-19: Meta-analysis.

ABSTRACT: Some have hypothesized that the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) may modify susceptibility to coronavirus disease-2019 (COVID-19) in humans. Thus, we conducted two meta-analyses to investigate the effect of ACEI and ARB on mortality and susceptibility to COVID-19. Pubmed and EMBASE were searched through June 2020 to identify clinical trials that investigated the testing positive and in-hospital mortality rates for COVID-19 for those who were treated with ACEI and/or ARB and for those who were not treated with ACEI or ARB. The first analysis investigated the testing positive rate of COVID-19. The second analysis investigated the in-hospital mortality rate for patients with COVID-19. Three eligible studies for the first analysis and 14 eligible studies for the second analysis were identified. The first analysis demonstrated that the use of ACEI or ARB did not affect the testing positive rates (odds ratio [OR] [confidence interval [CI]] = 0.96 [0.88-1.04]; p = .69, OR [CI] = 0.99 [0.91-1.08]; p = 0.35, respectively). The second analysis showed that the use of ACEI and/or ARB did not affect in-hospital mortality (risk ratio [RR] 95% [CI]] = 0.88 [0.64-1.20], p = 0.42). The subgroup analysis by limiting studies of patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in-hospital mortality compared with no ACEI or ARB use (RR [CI] = 0.66 [0.49-0.89], p = 0.004). Our analysis demonstrated that ACEI and/or ARB use was associated neither with testing positive rates of COVID-19 nor with mortality of COVID-19 patients.

SUBMITTER: Yokoyama Y

PROVIDER: S-EPMC7675602 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTo determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19.DesignRetrospective observational study.SettingMulticenter, international COVID-19 registry.SubjectsAdult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021.InterventionsNone.Measurements and main resultsData were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001).ConclusionsAmong patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.

Project description:ImportanceThe chronic receipt of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has been assumed to exacerbate complications associated with COVID-19 and produce worse clinical outcomes.ObjectiveTo conduct an updated and comprehensive systematic review and meta-analysis comparing mortality and severe adverse events (AEs) associated with receipt vs nonreceipt of ACEIs or ARBs among patients with COVID-19.Data sourcesPubMed and Embase databases were systematically searched from December 31, 2019, until September 1, 2020.Study selectionThe meta-analysis included any study design, with the exception of narrative reviews or opinion-based articles, in which COVID-19 was diagnosed through laboratory or radiological test results and in which clinical outcomes (unadjusted or adjusted) associated with COVID-19 were assessed among adult patients (≥18 years) receiving ACEIs or ARBs.Data extraction and synthesisThree authors independently extracted data on mortality and severe AEs associated with COVID-19. Severe AEs were defined as intensive care unit admission or the need for assisted ventilation. For each outcome, a random-effects model was used to compare the odds ratio (OR) between patients receiving ACEIs or ARBs vs those not receiving ACEIs or ARBs.Main outcomes and measuresUnadjusted and adjusted ORs for mortality and severe AEs associated with COVID-19.ResultsA total of 1788 records from the PubMed and Embase databases were identified; after removal of duplicates, 1664 records were screened, and 71 articles underwent full-text evaluation. Clinical data were pooled from 52 eligible studies (40 cohort studies, 6 case series, 4 case-control studies, 1 randomized clinical trial, and 1 cross-sectional study) enrolling 101 949 total patients, of whom 26 545 (26.0%) were receiving ACEIs or ARBs. When adjusted for covariates, significant reductions in the risk of death (adjusted OR [aOR], 0.57; 95% CI, 0.43-0.76; P < .001) and severe AEs (aOR, 0.68; 95% CI, 0.53-0.88; P < .001) were found. Unadjusted and adjusted analyses of a subgroup of patients with hypertension indicated decreases in the risk of death (unadjusted OR, 0.66 [95% CI, 0.49-0.91]; P = .01; aOR, 0.51 [95% CI, 0.32-0.84]; P = .008) and severe AEs (unadjusted OR, 0.70 [95% CI, 0.54-0.91]; P = .007; aOR, 0.55 [95% CI, 0.36-0.85]; P = .007).Conclusions and relevanceIn this systematic review and meta-analysis, receipt of ACEIs or ARBs was not associated with a higher risk of multivariable-adjusted mortality and severe AEs among patients with COVID-19 who had either hypertension or multiple comorbidities, supporting the recommendations of medical societies. On the contrary, ACEIs and ARBs may be associated with protective benefits, particularly among patients with hypertension. Future randomized clinical trials are warranted to establish causality.

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Association of renin-angiotensin-aldosterone system inhibitors with mortality and testing positive of COVID-19: Meta-analysis.

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