Experts cautious
However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.
Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.
“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”
Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.
“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”
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Dr. John McMurray
John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.
“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
New meta-analysis
The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.
The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.
The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”
In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.
“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
A version of this article originally appeared on Medscape.com.