ACEI/ARBs do not induce in-hospital mortality in COVID-19 patients

The use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) does not contribute to in-hospital mortality among patients with the novel coronavirus disease (COVID-19) and is safe in those with indications, suggests a Singapore study.

“This result concurs with the recommendations made by major international professional societies to not discontinue ACEI/ARB in patients with relevant indications,” the researchers said, adding that such finding will help guide physicians in caring for patients with COVID-19 on these medications.

All studies evaluating the use of ACEI/ARB and reporting the in-hospital mortality outcomes in COVID-19 patients were identified by searching PubMed, Embase, Google Scholar, and clinicaltrials.gov between 1 January 2020 and 30 May 2020. Nine nonrandomized studies were included in the analysis.

A total of 8,313 patients were involved, of whom 7,622 (91.7 percent) were from studies with all-comers, while 691 (8.3 percent) were from those with only hypertensive patients. There were 577 (14.6 percent) in-hospital deaths reported out of 3,949 patients with an outcome in the nine studies. [Singapore Med J 2020;doi:10.11622/smedj.2020159]

No significant difference was observed in in-hospital mortality between patients on ACEI/ARB and those not on the said medications (odds ratio [OR], 1.06, 95 percent confidence interval [CI], 0.75–1.50; p=0.73). Similar results were seen in sensitivity analyses in the hypertensive group (OR, 0.88, 95 percent CI, 0.58–1.32; p=0.53) and all-comers group (OR, 1.85, 95 percent CI, 1.00–3.43; p=0.05).

The findings that ACEI/ARB had no effect on in-hospital mortality in COVID-19 patients were consistent with the positional statement of major international professional societies, such as the American College of Cardiology, American Heart Association, Heart Failure Society of America, and European Society of Cardiology. [https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/positionstatement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang; https://www.acc.org/latest-incardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-usingraas-antagonists-in-covid-19]

The concerns on the effect of ACEI/ARB on the outcomes of COVID-19 patients stemmed from both previous and recent studies showing that angiotensin-converting enzyme 2 (ACE2) is the cellular entry point and mediator of infection and transmission not only in severe acute respiratory syndrome coronavirus (SARS-CoV), the coronavirus that caused the 2003 SARS outbreak, but also in SARS-CoV-2, the causative agent of COVID-19. [Nature 2003;426:450-454; Trends Pharmacol Sci 2004;25:291-294; Nature 2020;579:270-273]

“However, this concern regarding the use of ACEI/ARB in patients with COVID-19 has not been proven in clinical studies,” the researchers said. “At the same time, it has been postulated that ACEI/ARB may have a beneficial effect on patients with COVID-19, with evidence of downregulation of ACE2 expression by SARS-CoV-2.” [Sci China Life Sci 2020;63:364-374]

In addition, a previous study has shown that renin-angiotensin-aldosterone system (RAAS) activation plays a critical role in acute respiratory distress syndrome (ARDS). Another study reported that downregulation of ACE2 by SARS-CoV exacerbates lung injury in mice models, suggesting that RAAS system modulation could improve outcomes in ARDS. [Crit Care 2017;21:305; Nat Med 2005;11:875-879]

“Moreover, stopping essential medications that are guideline-recommended treatment for hypertension, heart failure, and kidney failure, among other indications, can have deleterious effects on patients’ blood pressure and haemodynamics,” the researchers said.