Safe to continue common BP meds in hospitalized COVID-19 patients: global trial data

Continuing RAS* inhibitors — a group of commonly used antihypertensive medications — was safe in patients hospitalized with COVID-19, without worsening clinical outcomes, the international REPLACE COVID randomized trial has shown.

“Consistent with international society recommendations, current evidence supports continuing RAS inhibitor therapy in patients admitted to hospital with COVID-19 unless there is a clear medical contraindication to ongoing therapy,” the investigators stated.

Early during the pandemic, there was widespread speculation that RAS inhibitors might increase susceptibility to COVID-19, leading to some patients requesting to stop their medications despite lack of evidence.

While subsequent data from observation studies indicate no excess risk overall in SARS-CoV-2 infection and disease severity in patients taking ACEIs or ARBs, the authors pointed out that “these studies could not address key sources of bias and confounding … and could not assess inpatient exposure to ACEI or ARB therapy following the onset of SARS-CoV-2 infection.”

“[The current study thus] provides high-quality evidence that adds to the findings of existing observational studies,” they added.

In the prospective, multinational, open-label REPLACE COVID trial, 152 participants (mean age 62 years, 45 percent female, 52 percent with diabetes) who were hospitalized with COVID-19 and were already on RAS inhibitors beforehand were randomized 1:1 to either continue or discontinue their RAS inhibitor medications. [Lancet Respir Med 2021;9:275-284]

Overall, the researchers found that continuing ACEI or ARB medications did not affect the severity of COVID-19 disease course. Patients who continued with their RAS inhibitors had similar primary outcomes, as evaluated using the global rank score which ranked four tiers** of outcomes hierarchically, compared with those who discontinued their medications (median rank, 73 vs 81; β-coefficient=8, 95 percent confidence interval [CI], -13 to 29).

There were also no differences in the secondary outcomes of need for intensive care or invasive mechanical ventilation (21 percent vs 18 percent), nor death between the two groups (15 percent vs 13 percent).

Furthermore, biochemical findings such as blood pressure, serum creatinine, or serum potassium were similar between the two groups over the entire course of follow-up.

“Our trial results importantly show that these medications can be safely continued for patients hospitalized with COVID-19,” said study principal investigator Dr Julio Chirinos of Perelman Center for Advanced Medicine, Philadelphia, Pennsylvania, US.

According to the authors, the current findings represent the first international randomized clinical trial to be published on continuation vs discontinuation of RAS inhibitors in hospitalized COVID-19 patients. The conclusions from this study were consistent with a previously presented but yet unpublished RCT, BRACE CORONA, which was single-country in design with a younger patient population and less comorbid — to which the authors noted, “might not be fully generalizable to patients typically admitted to hospital with COVID-19 and hypertension globally.”

“An important caveat for both studies is that the data most reliably apply to patients previously receiving ACEIs or ARB treatment for hypertension and associated conditions, other than for heart failure, which was an important exclusion criteria for both studies because of the higher perceived risk of withdrawing the benefits of RAS inhibition in patients with heart failure,” pointed out Dr Bryan Williams of University College London, London, UK, in a linked commentary. [Lancet Respir Med 2021;9:221-222]

“Ongoing trials will determine whether [initiating] these medications is effective for the treatment of COVID-19,” said Chirinos and co-authors.

*RAS: Renin–angiotensin system

**time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalization