Million+ Cases Suggest ACEIs, ARBs Don’t Increase COVID-19 Risk, Severity
Pharmacists now can give a definitive answer when worried patients on blood pressure medications inquire about the safety of ACEIS or ARBs during the pandemic. A review of more than a million cases internationally found no evidence that the drugs increased the risk of having a severe case of COVID-19. The results bolster recommendations that the therapy should not be discontinued related to COVID-19. Here are more details.
LOS ANGELES – In the chaotic days when the COVID-19 pandemic first began to affect the United States, pharmacists were barraged with questions about certain blood pressure medications and whether they increased infection risk for patients using them.
Now, the most comprehensive study yet finds no increased risk of COVID-19 diagnosis, hospitalization, or subsequent complications for users of either angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) among an international cohort of more than 1.1 million patients using antihypertensives.
The report in The Lancet Digital Health bolsters regulatory and clinical recommendations that patients should not discontinue ACE inhibitor or ARB therapy due to concerns of increased COVID-19 risk.
"People with hypertension have worse COVID-19 outcomes, and there remains speculation that some anti-hypertensive medications may be detrimental," explained research team leader Marc A. Suchard, says corresponding author Marc A. Suchard, MD, PhD, a professor at UCLA. "The clear answer is that ACE inhibitors and ARBs pose no increased risk as compared to other treatments."
For the international, open science, cohort analysis, Observational Health Data Sciences and Informatics (OHDSI) researchers used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify adults with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020.
The study defined users separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications.
Researchers assessed four outcomes:
- COVID-19 diagnosis;
- hospital admission with COVID-19;
- hospital admission with pneumonia; and
- hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis.
Results indicate that, among nearly 1.4 million antihypertensive users, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy vs. CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84–1·14) or combination use exposure (1·01, 0·90–1·15).
Researchers add that ACEIs alone showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68–1·21; with heterogeneity of >40%) or combination use (0·95, 0·83–1·07).
On the other hand, “directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79–0·99) and non-significant for monotherapy (0·85, 0·69–1·05),’ the authors note.
The study observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons.
“No clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19,” researchers conclude.
"Based on our results, if there is a risk difference, it's marginal and would be very challenging to further refine outside such a large-scale international study," Suchard added.
"By comparing people exposed to ACE inhibitor and ARBs against people taking other antihypertensives, either alone or in combination, using two methods across three database the study generated 1280 comparisons to assess the safety of these drugs, producing highly consistent results," advised lead author Daniel Morales, BMSc MBChB PhD, Wellcome Trust Clinical Research Fellow at the University of Dundee in Scotland.