Recently, the publication of several studies exploring the relationship of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with COVID-19 presented reassuring clinical data. Alhough all of the published studies are observational in design and have some confounding factors, overall the results do not indicate that continued utilization of ACE inhibitors and ARBs causes harm. However, there are some contradictory results in secondary analyses regarding possible variances in the effects of the two drug classes.

In one study, published in the New England Journal of Medicine, Mehra et al. utilized an observational database for 169 hospitals in Asia, Europe, and North America assess the relationship of cardiovascular disease and drug therapy with death among hospitalized patients with COVID-19 who were admitted between December 20, 2019, and March 15, 2020. Of the 8,910 patients with COVID-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. 

No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20-0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87-1.74). The researchers concluded that their study confirmed previous observations signifying that underlying cardiovascular disease is linked to an augmented risk of in-hospital death among patients hospitalized with COVID-19. The results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. 

In a second study published in the New England Journal of Medicine, Mancia et al conducted a population-based case–control study in the Lombardy region of Italy. A total of 6,272 case patients in whom infection with COVID-19 was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to gender, age, and municipality of residence.

Researchers indicated that among both case patients and controls, the mean (± SD) age was 68 ± 13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and nonantihypertensive drugs, and case patients had a worse clinical profile. The use of ARBs or ACE inhibitors did not show any association with COVID-19 among case patients overall (adjusted odds ratio, 0.95 [95% CI, 0.86-1.05] for ARBs and 0.96 [95% CI, 0.87-1.07] for ACE inhibitors) or among patients who had a severe or fatal course of disease (adjusted odds ratio, 0.83 [95% CI, 0.63-1.10] for ARBs and 0.91 [95% CI, 0.69-1.21] for ACE inhibitors), and no correlation between these variables was found according to gender. 

The study authors concluded that in this large, population-based study, the use of ACE inhibitors and ARBs was more common among patients with COVID-19 than among controls because of their higher incidence of cardiovascular disease. However, there was no indication that ACE inhibitors or ARBs affected the risk of COVID-19.

In a third study published in the New England Journal of Medicine, Reynolds et al analyzed data from the health records of 12,594 patients in the New York University (NYU) Langone Health system who had been tested for COVID-19. The researchers evaluated the relationship between previous treatment with ACE inhibitors, ARBs, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on COVID-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Among 12,594 patients who were tested for COVID-19, a total of 5,894 (46.8%) were positive; 1,002 of these patients (17.0%) had severe illness. 

A history of hypertension was present in 4357 patients (34.6%), of whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased probability of a positive test. The authors noted that none of the medications examined was linked to a significant increase in the risk of severe illness among patients who tested positive. Researchers concluded that there was no substantial increase in the likelihood of a positive test for COVID-19 or in the risk of severe COVID-19 among patients who tested positive in association with five common classes of antihypertensive medications.

These clinical data support current professional society guidelines to not discontinue ACE inhibitors  or ARBs in the setting of the COVID-19 pandemic. However, additional study in greater numbers of hospitalized patients receiving ACE inhibitor or ARB therapy is required to ascertain the correlation with clinical measures of COVID-19 severity.

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