At the beginning of the pandemic, cardiologists and cardiovascular patients were confused: could drugs from the group of ACE inhibitors and angiotensin receptor blockers be to blame for the fact that so many cardiovascular patients suffered a severe COVID-19 course? The drugs interfere with the renin-angiotensin system and upregulate the ACE2 receptor, which serves as a portal of entry for coronavirus - more receptor, more virus was the hypothesis. ACE inhibitors and angiotensin receptor blockers are among the most prescribed drugs worldwide and are used to treat arterial hypertension, heart failure, and diabetes mellitus, among other conditions.
Randomized study clarifies urgent question
A team from the Medical University of Innsbruck and LMU Hospital in Munich therefore investigated the question of whether temporary discontinuation of the drugs would have a positive effect on the course of COVID-19. "There was consensus in the professional community that only controlled, randomized intervention trials could clarify this urgent question," said the two responsible authors Axel Bauer, director of the University Department of Internal Medicine III at the Medical University of Innsbruck, and Steffen Massberg, director of the Medical Clinic and Polyclinic I at LMU Hospital.
The ACEI-COVID-19 study, funded by SARS-CoV-2 acute grants from the German Center for Cardiovascular Research (DZHK) and the Austrian Science Fund (FWF), ran from April 2020 to February 2021 at 35 centers in Germany and Austria. In the study, 204 cardiovascular patients acutely infected with SARS-Cov-2 were randomly divided into two groups. One group discontinued antihypertensive drugs for 30 days, while the other group continued taking them. In both groups, all relevant organ functions were determined daily by standardized tests to sensitively detect any effects.
Older pre-diseased patients could benefit
Stopping the drugs had no effect on the maximum severity of the disease. However, evidence showed that patients who paused recovered more quickly and better. For example, in the group with paused therapy, only half as many patients had organ damage or had died after 30 days. "In contrast to previous studies, which included significantly younger patients, our study provides evidence for the first time that older, previously ill individuals in particular could benefit from temporarily pausing therapy with ACE inhibitors or angiotensin receptor blockers," state Axel Bauer and Steffen Massberg.
However, the authors caution against generalizing the findings, saying, "It may make sense in individual cases to temporarily suspend therapy in the setting of acute COVID-19 disease. However, the decision must be made by a physician. Careful consideration must be given to the indication for medication, the availability of alternative therapies, and outpatient monitoring options. In any case, it is important to also restart taking the important medications after the disease has ended."
SARS-CoV-2 viruses enter the body's cells through receptors called angiotensin-converting enzyme (ACE) 2 receptors. These receptors are expressed not only in the lungs, but in numerous organs such as the heart, gastrointestinal tract and central nervous system. Experimental studies show that these receptors can be upregulated in various organ systems by ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB). This, in turn, could facilitate viral uptake and spread, thereby adversely affecting COVID-19 progression.
ACEI and ARB are among the most prescribed classes of drugs worldwide and are used to treat arterial hypertension, heart failure, and diabetes mellitus, among other conditions. Already at the beginning of the pandemic, it was noticed that severe COVID-19 disease courses were clustered in patients suffering from pre-existing conditions that are typically treated with ACEI/ARB. It was not clear to what extent an existing ACEI/ARB therapy plays a role in this.
Original work: Discontinuation versus continuation of renin-angiotensin system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial. Bauer A, Schreinlechner M, Vdovin N, Dolejsi T, Tilg H, Aulinger B A, Weiss G, Bellmann-Weiler R, Adolf C, Wolf D, Pirklbauer M, Graziadei I, Gänzer H, von Bary C, May A E, Wöll E, von Scheidt W, Rassaf T, Duerschmied D, Brenner C, Kääb S, Metzler B, Joannidis M, Kain H-U, Kaiser N, Schwinger R, Witzenbichler B, Alber H, Straube F, Hartmann N, Achenbach S, von Bergwelt-Baildon M, von Stulpnagel L, Schoenherr S, Forer L, Embacher-Aichhorn S, Mansmann U, Rizas K D, Massberg S for the ACEICOVID investigators. The Lancet Respiratory Medicine, June 11, 2021. DOI: https://doi.org/10.1016/S2213-2600(21)00214-9
Study: Stopping ACE-inhibitors in COVID-19 ACEI-COVID-19
Prof. Dr. med. Steffen Massberg, LMU Klinikum München, steffen.massberg(at)med.uni-muenchen.de.
Univ.-Prof. Dr. Axel Bauer, Medical University of Innsbruck, axel.bauer(at)i-med.ac.at