Commonly Used Blood Pressure Medications Such As ACE inhibitors (ACEIs) or Angiotensin Receptor Blockers (ARBs) Safe For COVID-19 Patients
A new international study lead by medical researchers from Perelman School of Medicine at the University of Pennsylvania has found that common medications used to treat high blood pressure did not affect outcomes among patients hospitalized with COVID-19. This study findings provides relief to many as during the initial phases of the COVID-19 pandemic, there were speculations that certain blood pressure medications could aggravate the conditions and disease progression for those infected with the SARS-CoV-2 coronavirus.
Initially biological considerations suggest that renin–angiotensin system inhibitors might influence the severity of COVID-19. The study team aimed to evaluate whether continuing versus discontinuing renin–angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.
The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin–angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin–angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin–angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov
Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin–angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin–angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40–110] for continuation vs
81 [38–117] for discontinuation; β-coefficient 8 [95% CI −13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups.
The study findings found that consistent with international socie
ty recommendations, renin–angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.
The study findings are published in the peer reviewed journal: Lancet Respiratory Medicine.
As part of the ongoing REPLACE COVID trial, the study team examined whether ACE inhibitors (ACEIs) or Angiotensin Receptor Blockers (ARBs) ie two classes of medications to treat high blood pressure could help mitigate complications or lead to more severe symptoms.
Currently more than 49 million U.S. adults take medication to treat hypertension, and among those, about 83 percent (41 million) take an ACEI or ARB, according to the Centers for Disease Control and Prevention.
In Thailand, it is estimated that about 1.1 million people are on such drugs.
In the beginning of the pandemic, a concern arose regarding the use of ACEIs or ARBs in the setting of COVID-19, since some studies had suggested that these medications could upregulate cellular receptors for the SARS-CoV-2 virus potentially aiding viral replication.
However, it was also considered that some effects of these medications could be protective against the virus. https://www.thailandmedical.news/news/coronavirus-news-french-study-shows-that-antihypertensive-drugs-could-lower-risk-of-deaths-in-high-risk-covid-19-patients
Corresponding and senior author Dr Julio A. Chirinos, MD, Ph.D., an associate professor of Cardiovascular Medicine in the Perelman School of Medicine told Thailand Medical News
, "Observational studies were rapidly done, but randomized trials are important to establish a definitive answer regarding the potential impact of these commonly used blood pressure medications in the setting of COVID-19. Our trial results importantly show that these medications can be safely continued for patients hospitalized with COVID-19."
These ACEIs and ARBs are among the most commonly prescribed medications in the world, and a potential link between those medications and COVID-19 outcomes has large global health implications.
To date several observational studies suggested no association between outpatient ACEI or ARB use and risk of COVID-19 hospitalization, but high-quality randomized trial evidence was lacking, until now.
As part of the ongoing REPLACE COVID trial, the study team enrolled 152 participants across several countries between March 31 and August 20, 2020, who were hospitalized with COVID-19 and already using one of the medications. The participants were randomly assigned to either stop or continue taking their prescribed medication and closely monitored to evaluate the effect of temporarily stopping the therapy.
The study team developed an innovative global rank score to classify patient outcomes based on four factors: time to death, length of time supported by mechanical ventilation or extracorporeal membrane oxygenation (ECMO), length of time on renal replacement therapy, and a modified sequential organ failure assessment score. Through analyzing the patient outcome data, the team found discontinuation of ACEIs and ARBs compared with continuation of these medications had no effect on the global rank score.
This new evidence supports international society recommendations for continuing ACEI and ARB therapy in patients admitted to the hospital with COVID-19, unless there is a clear, alternate medical issue with ongoing therapy.
First author Dr Jordana B. Cohen, MD, MSCE, an assistant professor in the division of Renal-Electrolyte and Hypertension, and a co-principal investigator with Dr Chirinos added, "At the start of the pandemic, patients were worried about perceived harm based on limited and incomplete information, and unfortunately, some insisted on stopping their medications. However, stopping these medications unnecessarily can increase the risk for severe complications, including heart attack and stroke. Now we have high quality evidence to support our recommendation that patients continue to take these medications as prescribed."
Presently, trials are even underway to determine if use of these medications is effective for the treatment of COVID-19.
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