In fact, ACE inhibitors were associated with a significant reduction in mortality (odds ratio [OR], 0.33), as were statins (OR, 0.35).
The authors, however, stress that these observations about reduced mortality with ACE inhibitors and statins “should be considered with extreme caution.”
“Because our study was not a randomized, controlled trial, we cannot exclude the possibility of confounding. In addition, we examined relationships between many variables and in-hospital death, and no primary hypothesis was prespecified; these factors increased the probability of chance associations being found. Therefore, a cause-and-effect relationship between drug therapy and survival should not be inferred,” they write.
A secondary analysis that was restricted to patients with hypertension (those for whom an ACE inhibitor or an ARB would be indicated) also did not show harm.
A second study published in the NEJM had a case-control design. The authors, led by Giuseppe Mancia, MD, University of Milano-Bicocca, Italy, compared 6272 patients with confirmed COVID-19 (case patients) with 30,759 control persons who were matched according to age, sex, and municipality of residence.
In a conditional logistic-regression multivariate analysis, neither ACE inhibitors nor ARBs were associated with the likelihood of SARS-CoV-2 infection.
“Thus, our results do not provide evidence of an independent relationship between renin angiotensin aldosterone blockers and the susceptibility to COVID-19 in humans,” the authors conclude.
In addition, a second analysis that compared patients who had severe or fatal infections with matched control persons did not show an association between ACE inhibitors or ARBs and severe disease.
In the third study published in the NEJM, a group led by Harmony R. Reynolds, MD, NYU Grossman School of Medicine, New York City, 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. They found 5894 patients whose test results were positive test. Of these patients, 1002 had severe illness, which was defined as illness requiring admission to the intensive care unit, need for mechanical ventilation, or death.
Using Bayesian analysis and propensity-score matching, the researchers assessed the relation between previous treatment with five different classes of antihypertensive drugs (ACE inhibitors, ARBs, beta blockers, calcium blockers, and 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 illness requiring intensive care, need for mechanical ventilation, or death) among patients who tested positive.