PMID- 33787911 OWN - NLM STAT- MEDLINE DCOM- 20210407 LR - 20210417 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 4 IP - 3 DP - 2021 Mar 1 TI - Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis. PG - e213594 LID - 10.1001/jamanetworkopen.2021.3594 [doi] LID - e213594 AB - IMPORTANCE: The 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. OBJECTIVE: To 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 SOURCES: PubMed and Embase databases were systematically searched from December 31, 2019, until September 1, 2020. STUDY SELECTION: The 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 SYNTHESIS: Three 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 MEASURES: Unadjusted and adjusted ORs for mortality and severe AEs associated with COVID-19. RESULTS: A 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 RELEVANCE: In 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. FAU - Baral, Ranu AU - Baral R AD - Department of Cardiology, Norfolk and Norwich University Hospital, Norwich, United Kingdom. AD - Department of Cardiology, Norwich Medical School, University of East Anglia, Norwich, United Kingdom. FAU - Tsampasian, Vasiliki AU - Tsampasian V AD - Department of Cardiology, Norfolk and Norwich University Hospital, Norwich, United Kingdom. FAU - Debski, Maciej AU - Debski M AD - Department of Cardiology, Norfolk and Norwich University Hospital, Norwich, United Kingdom. FAU - Moran, Brendan AU - Moran B AD - National Health Service 111 COVID-19 Clinical Assessment Service, Bicester, United Kingdom. AD - Neasden Medical Centre, London, United Kingdom. AD - Healix International, Esher, United Kingdom. FAU - Garg, Pankaj AU - Garg P AD - Department of Cardiology, Norfolk and Norwich University Hospital, Norwich, United Kingdom. AD - Department of Cardiology, Norwich Medical School, University of East Anglia, Norwich, United Kingdom. FAU - Clark, Allan AU - Clark A AD - Department of Medical Statistics, Norwich Medical School, University of East Anglia, Norwich, United Kingdom. FAU - Vassiliou, Vassilios S AU - Vassiliou VS AD - Department of Cardiology, Norfolk and Norwich University Hospital, Norwich, United Kingdom. AD - Department of Cardiology, Norwich Medical School, University of East Anglia, Norwich, United Kingdom. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20210301 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Antihypertensive Agents) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Angiotensin Receptor Antagonists/adverse effects/*pharmacology/therapeutic use MH - Angiotensin-Converting Enzyme Inhibitors/adverse effects/*pharmacology/therapeutic use MH - Antihypertensive Agents/adverse effects/*pharmacology/therapeutic use MH - COVID-19/epidemiology/*mortality MH - Comorbidity MH - Female MH - Humans MH - Hypertension/*drug therapy/epidemiology MH - Male MH - Middle Aged MH - *Renin-Angiotensin System MH - SARS-CoV-2 MH - *Severity of Illness Index PMC - PMC8013817 COIS- Conflict of Interest Disclosures: Dr Vassiliou reported receiving grants from the Norfolk Heart Trust and personal fees from Daiichi Sankyo and Novartis outside the submitted work. No other disclosures were reported. EDAT- 2021/04/01 06:00 MHDA- 2021/04/10 06:00 PMCR- 2021/03/31 CRDT- 2021/03/31 13:23 PHST- 2021/03/31 13:23 [entrez] PHST- 2021/04/01 06:00 [pubmed] PHST- 2021/04/10 06:00 [medline] PHST- 2021/03/31 00:00 [pmc-release] AID - 2777978 [pii] AID - zoi210134 [pii] AID - 10.1001/jamanetworkopen.2021.3594 [doi] PST - epublish SO - JAMA Netw Open. 2021 Mar 1;4(3):e213594. doi: 10.1001/jamanetworkopen.2021.3594.