Drugs to lower blood pressure of the type ACE inhibitors or angiotensin II receptor blockers reduce the mortality rate of influenza and pneumonia.
This is the main conclusion of a new reassuring study published in the Journal of the American Heart Association, which Christian Fynbo Christiansen and a number of Danish colleagues are behind. He is consultant, clinical associate professor and PhD at the Department of Clinical Epidemiology, which is part of the Department of Clinical Medicine at Aarhus University and Aarhus University Hospital in Denmark.
In the study, the researchers have compared mortality rates among 500,000 Danish patients who were admitted to hospitals in Denmark with influenza and pneumonia during the period 2005 to 2018. This has been done by correlating information from the National Patient Register (activity at Danish hospitals) with statistics from the Danish Register of Medicinal Products (the consumption of medicine in Denmark).
"A little over 100,000 of the admitted patients took ACE inhibitors or angiotensin II receptor blockers, and the study shows that fewer of them were put on a ventilator and that they had lower mortality rates than the hospitalised patients who took another type of drugs against elevated blood pressure, calcium blockers," says Christian Fynbo Christiansen.
The study arrives mid in a discussion of treatment which peaked while the corona pandemic was at its height. Some medical doctors and researchers pointed out that ACE inhibitors may actually have the completely opposite effect - that is increasing the risk of dying from COVID-19 as the virus SARS-CoV-2 which causes COVID-19 enters the lungs through the same ACE receptors as the ACE inhibitors.
The hypothesis was that when the ACE inhibitor reduces the level of ACE, the body compensates for this by activating a much greater number of ACE receptors on the surface of the cells, which the SARS-CoV-2 virus then utilises as some kind of access key. The greater the number of access keys available on the surface of the cells, the more easily the virus gains access to the cells.
The theory about increased mortality has been nurtured by the fact that a strikingly large proportion of the patients who were seriously ill due to COVID-19 had elevated blood pressure, which is extensively treated with ACE inhibitors - of the 600,000 Danes who have elevated blood pressure, approximately one-third ( 200,000) of them take ACE inhibitors.
"We haven't examined whether what applies to patients with influenza and pneumonia can be transferred directly to patients with COVID-19, but there is some evidence to suggest that ACE inhibitors have a protective effect against lung damage which we don't see in patients who take other types of medicine to lower blood pressure. The first studies find no correlation between ACE inhibitors/angiotensin II receptor blockers and COVID-19. However, further studies are needed using the good Danish registers," says Christian Fynbo Christiansen.
In Denmark, the discussion for and against the use of ACE inhibitors on corona patients has taken place (in Danish) in e.g. the Journal of the Danish Medical Association and another healthcare newspaper Dagens Medicin under headlines such as 'ACE inhibitors possibly increase the risk of dying of COVID-19'.
Facts: What are ACE inhibitors and angiotensin II receptor blockers?
ACE inhibitors are a group of drugs which expand the blood vessels so that blood pressure is lowered and the work done by the heart becomes easier. An ACE inhibitor dampens the enzyme in the body which ensures that the inactive angiotensin I is converted into the active angiotensin II. Angiotensin II causes contraction of the blood vessels. When the body forms less angiotensin II, the blood vessels relax and blood pressure decreases. The acronym ACE stands for Angiotensin Converting Enzyme. As the name suggests, angiotensin II blockers work directly on angiotensin II.
The research results - more information
The study is a register-based study of more than 500,000 Danes who were hospitalised during the period 2005-2018 with influenza and pneumonia. Data has been correlated with the Danish Register of Medicinal Products, where information was retrieved on the use of medicine to lower blood pressure. By correlating the National Patient Register and the civil registration number (CPR) register, it was possible to study intensive care hospitalisation, ventilator treatment and mortality.
The partners involved in the project include Michael Mæng from the Department of Clinical Medicine and the Department of Cardiology and Ole Schmeltz Søgaard from the Department of Clinical Medicine and the Department of Infectious Diseases, both of which are at Aarhus University and Aarhus University Hospital. Additional partners include Jacob Bodilsen from the Department of Infectious Diseases at Aalborg University Hospital/Aalborg University, as well as Anton Pottegård and Jesper Hallas from Clinical Pharmacology and Pharmacy at the University of Southern Denmark. Another important partner is Nikolai C. Brun from the Danish Medicines Agency.
The study has not received any external funding.
None of the authors have any conflicts of interest. The institutions receive grants from different companies in the form of research grants, but none of these have any relation to the present study.