COVID-19 Resource Center
COVID-19 Resource Center
Source/Disclosures
Disclosures: Cohen reports she received consultant honoraria from Bayer, Bristol Myers Squibb, Edwards Lifesciences, Johnson & Johnson and Sanifit; research grants from Bristol Myers Squibb, Fukuda Denshi, Microsoft and the NIH; compensation from the AHA and the American College of Cardiology; and speaking honoraria from the University of Utah and Washington University. Chirinos reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
January 08, 2021
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Renin-angiotensin inhibitors safe in patients hospitalized with COVID-19: REPLACE COVID

Source/Disclosures
Disclosures: Cohen reports she received consultant honoraria from Bayer, Bristol Myers Squibb, Edwards Lifesciences, Johnson & Johnson and Sanifit; research grants from Bristol Myers Squibb, Fukuda Denshi, Microsoft and the NIH; compensation from the AHA and the American College of Cardiology; and speaking honoraria from the University of Utah and Washington University. Chirinos reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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It is safe for patients hospitalized with COVID-19 to continue using renin-angiotensin system inhibitors, researchers reported.

The REPLACE COVID trial, published in The Lancet Respiratory Medicine, is consistent with the findings of the BRACE-CORONA trial, which, as Healio previously reported, found there was no benefit to suspending ACE inhibitors or angiotensin receptor blockers in patients hospitalized with mild or moderate COVID-19.

COVID-19
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According to the researchers, REPLACE COVID was launched after several research and press articles circulated early in the COVID-19 pandemic raising the suggestion of these medications possibly upregulating viral receptors, prompting safety concerns about the use of these medications in patients with COVID-19.

Jordana B. Cohen

“Given that over 40 million people in the U.S. are prescribed these medications, we felt that it was critical to have high-quality, randomized trial evidence to inform us regarding the safely of ongoing use of these medications in patients who fall ill with COVID-19,” Jordana B. Cohen, MD, assistant professor from the renal-electrolyte and hypertension division and department of biostatistics, epidemiology and informatics at Perelman School of Medicine at the University of Pennsylvania, told Healio. “Our trial, along with other available evidence, establishes that it is safe to continue these medications in hospitalized COVID-19 patients who require them for various reasons.”

Researchers conducted the prospective, randomized, open-label trial performed at 20 large referral hospitals in seven countries from March 31 to Aug. 20. The trial included 152 participants (mean age, 62 years; 45% women) aged 18 years and older admitted to the hospital with COVID-19 who were receiving a renin-angiotensin system inhibitor before admission. Participants were randomly assigned to continuation of their renin-angiotensin system inhibitor (n = 75) or discontinuation (n = 77).

The primary outcome was a global rank score of participants ranked across four hierarchical tiers such as time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy and multiorgan dysfunction during hospitalization.

Continuation of renin-angiotensin system inhibitors had no effect on the global rank score compared with discontinuation (median rank, 73 for continuation vs. 81 for discontinuation; beta coefficient = 8; 95% CI, –13 to 29; P = .61). ICU admission or invasive mechanical ventilation was required among 21% of participants in the continuation group compared with 18% in the discontinuation group (P = .61).

There were no differences between the groups in length of hospital stay (P = .56), length of ICU stay/invasive mechanical ventilation time (P = .59) or area under the curve of the Sequential Organ Failure Assessment score adjusted for death (P = .38).

In the continuation group, 15% of patients died compared with 13% in the discontinuation group (P = .99). At least one adverse event was reported by 39% of participants in the continuation group and 36% of participants in the discontinuation group (P = .77).

Researchers observed no difference in BP, serum potassium or creatinine during follow-up in both groups.

According to a press release issued by Penn Medicine, the results support international society recommendations for continuing ACE inhibitors and angiotensin receptor blockers in patients hospitalized with COVID-19, unless a clear, alternate medical issue with ongoing therapy is noted.

Julio Chirinos

“We are awaiting the results of several ongoing studies that are evaluating if new initiation of these medications may actually be helpful to treat COVID-19,” Julio Chirinos, MD, associate professor of medicine in the division of cardiovascular medicine at the Hospital of the University of Pennsylvania and Perelman School of Medicine at the University of Pennsylvania, told Healio. “Future research may also be helpful to identify if there is a difference between ACE inhibitors vs. angiotensin receptor blockers in the setting of COVID-19, which our study did not address.”

For more information:

Julio Chirinos, MD, can be reached at julio.chirinos@uphs.upenn.edu; Twitter: @juliochirinosmd.

Jordana B. Cohen, MD, can be reached at jco@pennmedicine.upenn.edu; Twitter: @jordy_bc.