Background: and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. Methods: We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms "(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)". The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. Results: Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p ¼ 0.34; I 2 : 81%) and severity (OR 1.03 [0.73, 1.45], p ¼ 0.87; I 2 : 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p ¼ 0.38; I 2 : 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p ¼ 0.02; I 2 : 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p ¼ 0.16; I 2 : 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p ¼ 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. Conclusion: Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.

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