People with one type of irregular heartbeat (called atrial fibrillation) do not benefit from a drug called spironolactone. A new trial called IMPRESS-AF found that the drug does not offer benefits and could even be harmful. Spironolactone offered no improvements in exercise capacity, heart function, or quality of life. In fact, the treatment significantly worsened kidney function.
People with atrial fibrillation are more likely than others to develop heart failure (when the heart is unable to supply sufficient blood to the body). In about half of these people, the heart walls are stiff and do not relax normally between heartbeats. This means that the heart does not fill with oxygenated blood. The heart muscle is able to pump the reduced volume of blood around the body (this is called preserved ejection fraction) but the supply of oxygen to the body is insufficient. People with this condition have a poor quality of life and a high risk of death.
Spironolactone is already given to people with high blood pressure, and to those with heart failure in which the heart is not able to pump sufficiently. There were hopes that the drug could be an effective in atrial fibrillation with preserved ejection fraction. But the new study suggests those hopes are unfounded.
What’s the issue?
Many people with atrial fibrillation get out of breath quickly, which means their quality of life is poor and they have a high risk of premature death. The condition is hard to treat and there is a clear need to find new therapies.
Early reports suggested that spironolactone is likely to help, but before this study, it had not been rigorously tested.
The IMPRESS-AF trial (Improved exercise tolerance in heart failure with preserved ejection fraction by spironolactone on myocardial fibrosis in atrial fibrillation) included 250 people with atrial fibrillation and preserved ejection fraction. Most were in their 70s and three-quarters were men. Half were randomly assigned to receive spironolactone for two years and the others took a dummy pill (placebo). Neither researchers nor participants knew which pill had been given.
The investigators measured exercise tolerance, quality of life and heart function.
The results showed:
- there was no difference in outcomes between those who were given spironolactone and those who were not
- people taking spironolactone were just as likely to become out of breath when cycling or walking
- the drug significantly reduced kidney function over two years of treatment.
The researchers concluded that there should be no further testing of spironolactone for atrial fibrillation with preserved ejection fraction.
Why is this important?
The results show that a possible therapy for a dangerous and difficult to treat heart condition is not effective. The study was relatively small – just 125 people were given the drug – but the results are conclusive and further testing is unjustified.
Scientists and cardiologists will look elsewhere for new treatments as they continue to seek ways to help these often elderly and vulnerable people.
The results should effectively close down research on spironolactone for atrial fibrillation with preserved ejection fraction, the study authors say. There was no trend towards improvement in exercise tolerance or quality of life. They conclude that it is unlikely that a larger study would change the outcome in patients with this type of atrial fibrillation.
You may be interested to read
The full study: Shantsila E, and others. Spironolactone to improve exercise tolerance in people with permanent atrial fibrillation and preserved ejection fraction: the IMPRESS-AF RCT. Efficacy and Mechanism Evaluation. 2020;7:1-68
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This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and NIHR partnership.