01 Apr Blood Pressure Meds ACEIs and ARBs and COVID-19 Infection
MedicalResearch.com Interview with:
Fabian Sanchis-Gomar, MD, MSc, PhD
Department of Medicine
Stanford University Medical Center
Department of Physiology, School of Medicine, University of Valencia
INCLIVA Biomedical Research Institute
MedicalResearch.com: What is the background for this study? How does the RAAS system interface with the COVID-19 virus?
Response: Angiotensin-converting enzyme (ACE)2 is a functional receptor for coronaviruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The exponential growth of contagion by the SARS-CoV-2 all around the world has contributed to raising speculations and concerns about whether two commonly used anti-hypertensive drugs, i.e., ACE inhibitors and angiotensin receptor blockers (ARBs), have positive or negative effects in coronavirus disease 2019 (abbreviated “COVID-19”) patients with arterial hypertension on-going treatment with some of the former drugs.
In effect, many professional health organizations have published statements claiming that there is not enough evidence to change the use of ACE-inhibitors or ARBs for the management of raised blood pressure (BP) in the context of avoiding or treating COVID-19 infection.
MedicalResearch.com: What are the main findings?
Response: Current evidence shows that the renin-angiotensin-aldosterone system (RAAS) inhibitors, i.e., ACE inhibitors and ARBs, reduce mortality in cardiovascular disease, becoming the cornerstone of heart failure and hypertension treatment. ACE-inhibitors or ARB therapy should be maintained or initiated in patients with heart failure, hypertension, or myocardial infarction, regardless of SARSCoV2. No differences exist between ARBs and ACEIs in terms of efficacy to decrease blood pressure and improve other outcomes. However, a cough sometimes associated with the use of ACEIs, and withdrawal rates due to adverse events are lower with ARBs. Therefore, given equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in COVID-19 patients at higher risk for developing severe forms of the disease.
MedicalResearch.com: Don’t ACE inhibitors have different effects on ACE 2 levels vs the effects of ARBs on ACE 2 levels, since ARBs affect angiotensin 2 receptors and ACE inhibitors inhibit ACE? If this is so, why is there not a differentiation between ACE inhibitors and ARBs in the COVID-19 discussions?
Response: To date, no studies have reported an increase in circulating ACE2 levels or expression. Besides, an increased expression would not necessarily imply an increased risk of infection or disease severity, although further studies are needed to clarify this.
MedicalResearch.com: Can you comment further on the Losartan study on COVID-19?
Response: I presume you refer to the study recently started in patients with COVID-19 requiring hospitalization (ClinicalTrials.gov Identifier: NCT04312009). In brief, this is a multi-center, double-blinded study in which the investigators compare the effects of Losartan or placebo administration for 7 days or hospital discharge in COVID-19 infected patients requiring hospital admission.
The primary outcome is the Sequential Organ Failure Assessment (SOFA) Respiratory Score. The investigators are also measuring many other secondary outcomes such as mortality, respiratory failure requiring artificial ventilation, length of hospital stay, ICU admission or ICU length of stay, among others. We will know the results of this study soon.
MedicalResearch.com: What should readers take away from your report?
Response: Patients with hypertension should keep taking antihypertensive medication and do not interrupt it under no circumstances. No difference exists between ARBs and ACE inhibitors in terms of efficacy to decrease BP and other outcomes such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. ACE inhibitors are associated with cough secondary to accumulation of bradykinin and angioedema, while withdrawal rates due to adverse events are lower with ARBs. Given the equal efficacy but fewer adverse events, ARBs may be a more favorable treatment option in COVID-19 patients at higher risk of developing severe forms of disease.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: To further evaluate the role of RAAS modulation in COVID-19, datasets should be analyzed to investigate if use of ACE inhibitors and ARBs on admission could be associated with acute lung injury/ acute respiratory distress syndrome and/or mortality in patients with diabetes, hypertension and cardiovascular disease.
MedicalResearch.com: Is there anything else you would like to add?
Response: We have started a randomized clinical trial to evaluate the effects of these drugs in this scenario. New results are coming soon.
Sanchis-Gomar F, Lavie CJ, Perez-Quilis C, Henry BM, Lippi G. Angiotensin-converting enzyme 2 and anti-hypertensives (angiotensin receptor blockers and angiotensin converting enzyme inhibitors) in coronavirus disease 2019 (COVID-19) [published online ahead of print March 30, 2020]. Mayo Clin Proc. http://doi.org/10.1016/j.mayocp.2020.03.026.
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