The effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on death and severity of disease in patients with coronavirus disease 2019 (COVID-19): A meta-analysis

Aims and Methods

Effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on outcomes in patients with coronavirus disease 2019 (COVID-19) is uncertain. Available evidence is limited to a few retrospective observational studies with small number of patients. We did a meta-analysis to assess the effect of ACEi/ARB in patients with COVID-19 on severity of disease, risk for hospitalisation, and death compared to those not on ACEi/ARB. We searched the Cochrane library, PubMed, Embase, ClinicalTrial.gov and medRxiv for studies published until 25.04.2020. Inclusion criteria included all studies with patients with confirmed COVID-19 either taking, or not taking, ACEi/ARB. Depending on degree of heterogeneity, fixed or random effect model was selected to calculate effect size (Odds ratio).

Results

Six studies were eligible for this meta-analysis. These included 423 patients on ACEi/ARB, and 1419 not on ACEi/ARB. Compared to patients with COVID-19 not on ACEi/ARB, there was a statistically significant 43% reduction (OR 0.57, CI: 0.37–0.88, I ² : 0.000) in the odds of death in those on ACEi/ARB. There was a statistically non-significant 38% reduction (OR: 0.62, 95% CI: 0.31–1.23, I ² =70.36) in the odds of developing severe disease and 19% reduction (OR 0.81; 95% CI: 0.42–1.55, I ² : 0.000) in the odds of hospitalisation among those on ACEi/ARB.

Discussion

It is safe to use ACEi/ARB in patients with COVID-19 requiring these medications for associated comorbidities. Although limited by confounding factors typical of a meta-analysis of retrospective observational studies, our data suggests that use of these medications may reduce the odds of death.

Conclusion

Our meta-analysis of the updated studies on SARS-CoV-2 reassures the medical fraternity on the use of and continuation of ACEi/ARB, supporting all recent recommendations.

Evidence before this study

• The postulated dual role of angiotensin-converting enzyme (ACE) inhibitors (ACEi) and angiotensin receptor blockers (ARB) in patients with coronavirus disease 2019 (COVID-19) has created a dilemma for clinicians.

• On the one hand, there is speculation that by upregulating ACE2, ACEi/ARBs might increase the risk and severity of COVID-19.

• On the other hand, there is evidence that downregulation of ACE2 can mediate acute lung injury. Further evidence is urgently needed to guide clinicians in the use of ACEi/ARB in patients with COVID-19 with co-morbidities.

What does this article add

• Our meta-analysis, which is the first to assess the effect of use of ACEi/ARB in patients with COVID-19, reports that use of ACEi/ARB statistically significantly reduced the risk of death, with a trend towards reduction in risk of severe disease and hospitalisation compared to those who were not on ACEi/ARB.

• Further information from on-going RCTs shall take time to fruition; in the interim, based on these findings, clinicians can safely continue to use ACEi/ARB in patients with COVID-19 with comorbidities.

Review Criteria

• A web-based search was conducted using the Cochrane library, PubMed, Embase, ClinicalTrial.gov and medRxiv using specific keywords.

• Narrowing down of the citations was done based on full text availability and a set of pre-determined inclusion criteria.

• Meta-analysis was conducted on the pooled data comparing ACEi/ARB group versus the non-ACEi/ARB group on death, severity of disease and hospitalization using the CMA software version 3, Biostat Inc., Englewood, NJ, USA.

• Effect size was reported as odds ratio with a 95% confidence interval and the degree of heterogeneity of the pooled data.

Message for the clinic

• There is no indication from present evidence to withhold or withdraw ACEi/ARB in patients with SARS-CoV-2.