Preclinical evidence and observations have yielded mixed conclusions, but a new clinical study finds no negative effect to medication continuation.
New research finds no evidence that patients taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) should discontinue those therapies if they are hospitalized with coronavirus disease 2019 (COVID-19).
The impact, or lack thereof, of ACEIs and ARBs has been an open question due to conflicting hypotheses and observations in the COVID-19 era, according to corresponding author Renato D. Lopes, MD, PhD, of the Duke Clinical Research Institute, and colleagues.
“Membrane-bound angiotensin-converting enzyme 2 (ACE2), an enzyme that physiologically counters renin-angiotensin-aldosterone system (RAAS) activation, is the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 pandemic,” Lopes and colleagues explained.
Preclinical investigation has suggested that RAAS inhibitors, such as ACEIs and ARBs, up-regulate ACE2 expression, which hypothetically could put patients with COVID-19 at higher risk. However, the investigators noted that observational evidence has suggested the therapies might actually have a positive impact, by decreasing acute lung damage and preventing angiotensin II-mediated pulmonary permeability, inflammation, and fibrosis.
Lopes and colleagues decided to attempt to solve the question with a randomized clinical trial in which patients hospitalized with mild to moderate COVID-19 who were taking ACEIs and ARBs prior to hospitalization were studied based on one of two scenarios: discontinuation of the ACEI or ARB therapy, or continuation. Their findings were published in the Journal of the American Medical Association.
A total of 659 patients were recruited, each of whom sought care for COVID-19 infection in one of 29 participating Brazilian hospitals. The patients were included in a national registry of confirmed and suspected COVID-19 cases. Three hundred and thirty-four patients discontinued ACEI or ARB therapy during their hospitalizations, and the remaining 325 patients continued with the drugs. The median age of the patients was 55.1 years, and 6 in 10 were male. The patients were hospitalized 6 days after symptom onset, on average, and 57.1% of cases were considered mild cases of COVID-19, with the remaining categorized as moderate cases. The primary outcome was days alive and outside the hospital after 30 days; secondary outcomes included death, cardiovascular death, and COVID-19 disease progression.
After 30 days, patients in the discontinuation group had an average number of days alive and out of the hospital of 21.9 days, versus 22.8 days for the continuation group. Rates of death were also similar, 2.7% and 2.8% for the discontinuation and continuation groups, respectively.
Cardiovascular death and disease progression likewise were statistically similar between both groups. The most common adverse events were respiratory failure requiring ventilation, shock requiring vasopressors, and acute myocardial infarction, among others. In most cases, the adverse event rates were similar, but slightly higher, in the discontinuation group.
“In this pragmatic, registry-based randomized clinical trial, discontinuing ACEI or ARB therapy for 30 days did not affect the number of days alive and out of the hospital in patients hospitalized with mild to moderate COVID-19,” the investigators said.
Lopes and colleagues added that existing evidence suggests that when long-term medications are discontinued during hospitalization, clinical inertia can result in a failure to resume the therapies following hospitalization. In the case of hypertension, that could lead to significantly worse long-term outcomes, they said.
“The results of this trial support the continued use of ACEIs or ARBs in patients hospitalized with COVID-19,” the authors concluded.