Influence of angiotensin converting enzyme inhibitors/angiotensin receptor blockers on the risk of all-cause mortality and other clinical outcomes in patients with confirmed COVID-19: A systemic review and meta-analysis

Abstract

Since the COVID-19 pandemic, physicians concerned about the potential adverse effects of angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs). To explore the relationship between ACEIs/ARBs and the risk of mortality and other clinical outcomes in COVID-19 patients, the authors conducted a systemic review and meta-analysis. An electronic search was performed from inception to November 12, 2020 in PubMed, Medline, EMBASE, ClinicalTrials, TRIP, the Cochrane Library, CNKI, Wanfang, and CBM database. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Interventions tool. The primary outcome was in-hospital all-cause mortality. Secondary outcomes included all-cause mortality measured at 30-day or longer term, mechanical ventilation, length of hospital stay, readmission, and cardiac adverse events. A total of 28 studies with 73 465 patients was included. Twenty-two studies with 19 871 patients reported the incidence of all-cause mortality. Results showed no association between using ACEIs/ARBs and risk of mortality crude odds ratio （OR） of 1.02, 95% CI 0.71-1.46, p = .90, I² = 88%, adjusted OR in 6260 patients of 0.96, 95% CI 0.77-1.18, p = .68, I² = 0%. While six studies with 10 030 patients reported a lower risk of mortality in ACEIs/ARBs group hazard ratio (HR) of 0.53, 95% CI 0.34-0.84, p = .007, I² = 68%. Similar association (for HR) was found in hypertension subgroup. There was no significant association for the secondary outcomes. Based on the available data, we concluded that ACEIs/ARBs is not associated with the risk of in-hospital all-cause mortality in COVID-19 patients, but may be associated with a decreased risk of 30-day all-cause mortality. Patients with hypertension may benefit from using ACEIs/ARBs.

Keywords: COVID-19; angiotensin converting enzyme inhibitor; angiotensin receptor blocker; mortality.

FIGURE 1

Flow diagram showing the identification of eligible trials and participating trials. A PRISMA flow diagram of the full study‐selection process was shown

FIGURE 2

Association between ACEI/ARB use and in‐hospital all‐cause mortality. Pooled risk of in‐hospital all‐cause mortality was shown as crude OR (A), adjusted OR (B), and HR (C) Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; HR, hazard ratio; OR, odd ratio.

FIGURE 3

Association between ACEI/ARB use and in‐hospital all‐cause mortality with hypertension subgroup. Pooled risk of in‐hospital all‐cause mortality was shown as crude OR (A), adjusted OR (B), and HR (C). Population were divided into mix population and hypertensive population. Some studies provided the effect size of overall population and hypertension subgroup. The effect size was pooled separately. Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; HR, hazard ratio; OR, odd ratio.

FIGURE 4

Association between ACEI or ARB use alone and in‐hospital all‐cause mortality. Pooled risk of in‐hospital all‐cause mortality was shown as crude OR (A), adjusted OR (B), and HR (C). Studies were divided into ACEI subgroup and ARB subgroup. The effect size was pooled separately Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; HR, hazard ratio; OR, odd ratio.