A Population-Based Study Showed No Association Between COVID-19-Induced In-Hospital Death and Angiotensin-Converting–Enzyme Inhibitors and Angiotensin-Receptor Blockers Use

Sahar Memar Montazerin, MD
By Sahar Memar Montazerin, MD on

A recent study by Dr. Mehra, published in the New England Journal of Medicine, disapproved of the previously concerning idea regarding the potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in the clinical context of Coronavirus disease 2019 (Covid-19). This study also demonstrated that Covid-19 may disproportionately affect individuals with cardiovascular disorders.

As the Covid-19 pandemic has spread all over the world, there has been growing evidence indicating that individuals with cardiovascular disorders are more prone to be affected and may manifest a more severe course of the disease. Interestingly, the causative agent of this viral infection uses angiotensin-converting enzyme 2 (ACE2) of the host cells as a receptor to invades the human cells. These ACE2 receptors are predominantly expressed in the heart, intestine, kidney, and pulmonary alveolar (type II) cells. This viral tendency to ACE2 is especially worrisome because patients receiving ACE inhibitors or ARBs may have increased expression of ACE2 that may lead to more severe infection and adverse outcomes during the Covid-19 disease course.

This observational study was done using data from an international database, Surgical Outcomes Collaborative registry. It included data from 169 hospitals located in 11 countries all over the globe. The study resulted in data from 8910 patients with polymerase-chain-reaction (PCR)–proven Covid-19 patients who were admitted to the hospital between December 20, 2019, and March 15, 2020.

Participants’ mean age was 49±16 years (16.5% of the patients were >65 years of age) and 40.0% of the patients were women. Of the total participants of the study, 5.8% (515 individuals) died in the hospital and the rest of them survived to be discharged. The cardiovascular factors associated with a higher risk of in-hospital death included coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio: 2.70; 95% Confidence Interval (CI): 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio: 2.48; 95% CI:1.62 to 3.79), and cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio: 1.95; 95% CI: 1.33 to 2.86). Other factors associated with increased in-hospital death were age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio: 1.93; 95% CI: 1.60 to 2.41), a history of chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio: 2.96; 95% CI: 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio: 1.79; 95% CI: 1.29 to 2.47).

The study confirmed the previously suggested notion that individuals with underlying cardiovascular disease are at increased risk of in-hospital death from Covid-19 disease. It was unable to show the harmful effect of ACE inhibitors and ARBs in the context of this viral infection. In contrast, it showed a better survival rate among those Covid-19 patients who were using either statins or ACE inhibitors. Also, it demonstrated that the female gender was associated with a better survival rate, independent of older age. The results of this study should be interpreted with extreme caution as it may be modified by the potential confounding factors.

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