Effects of Renin-Angiotensin System Inhibitors on Mortality and Disease Severity of COVID-19 Patients: A Meta-analysis of Randomized Controlled Trials.

Background: There is controversy over the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on the prognosis in patients with coronavirus disease 2019 (COVID-19), therefore, we aim to further explore the effect of renin-angiotensin-aldosterone system inhibitors on COVID-19-associated disease severity and mortality.

Methods: We systematically searched PubMed, Embase, Cochrane Library databases, medRxiv, and bioRxiv from inception to 6 September 2021. The primary outcome was all-cause mortality. Secondary outcome was severe disease which was defined as admission to the intensive care unit, the use of noninvasive or invasive mechanical ventilation, or death.

Results: A total of 7 randomized controlled trials involving 1,321 COVID-19 patients were included. Fixed-effects meta-analysis demonstrated that the use of ACEI/ARB was not associated with higher risk of mortality (risk ratio [RR] = 0.84, 95% confidence interval [CI] 0.57-1.22, P = 0.10, I2 = 43%) and disease severity (RR = 0.86, 95% CI 0.71-1.05, P = 0.11, I2 = 47%). However, the subgroup analysis showed that compared with no ACEI/ARB use, the use of ARB was associated with a significant reduction of mortality (RR = 0.23, CI 0.09-0.60, P = 0.55, I2 = 0%) and disease severity (RR = 0.38, CI 0.19-0.77, P = 0.007).

Conclusions: In conclusion, based on the available data, ACEI/ARB is not associated with the risk of mortality and disease severity in COVID-19 patients. And ACEI/ARB medications, especially ARB, should not be discontinued for patients with COVID-19.