Association of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with risk of COVID‐19, inflammation level, severity, and death in patients with COVID‐19: A rapid systematic review and meta‐analysis

Abstract An association among the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin‐receptor blockers (ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID‐19) is unclear. PubMed, EMBASE, MedRxiv, and BioRxiv were searched for relevant studies that assessed the association between application of ACEI/ARB and risk of COVID‐19, inflammation level, severity COVID‐19 infection, and death in patients with COVID‐19. Ten studies were included with 13,944 patients. ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin‐6) and elevated immune cells counts (CD3, CD8). Meta‐analysis showed no significant increase in the risk of COVID‐19 infection (odds ratio [OR]: 0.95, 95% CI: 0.89‐1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID‐19 (OR: 0.75, 95% CI: 0.59‐0.96, p  = 0.02) and mortality (OR: 0.57, 95% CI: 0.37‐0.87, p  = 0.009). Subgroup analyses showed among the general population, ACEI/ARB therapy was not associated with reduced risks of severe COVID‐19 infection (OR: 0.85, 95% CI: 0.66‐1.08, p  = 0.19) and all‐cause mortality (OR: 0.31, 95% CI: 0.13‐0.75), and COVID‐19 infection (OR: 0.97, 95% CI: 0.89‐1.05, p  = 0.45) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a non‐significant lower severity of COVID‐19 (OR: 0.73, 95% CI: 0.51‐1.03, p  = 0.07) and significant lower mortality (OR: 0.57, 95% CI: 0.37‐0.87, p  = 0.009), without evidence of an increased risk of COVID‐19 infection (OR: 1.00, 95% CI: 0.90‐1.12, p  = 1.00). On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID‐19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well‐designed studies that control the clinical confounders are necessary to confirm our findings.