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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.

What’s new?

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.

What’s next?

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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Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and NIHR partnership.

Conflicts of Interest: Some authors have received fees and funding from various pharmaceutical companies and device manufacturers.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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Study author

We are obviously disappointed that spironolactone did not help these patients. Experimental work and pre-clinical data suggested it was the right drug for these patients and we were hopeful. We’re desperate to find a treatment for atrial fibrillation.

The results were unexpected. We wanted to help people but spironolactone is not the answer.  The results conclusively show that it should not be used. Research on this drug is not going anywhere.

Eduard Shantsila, Honorary Senior Lecturer in Cardiovascular Science, University of Liverpool


The paper provides evidence that although spironolactone can reduce stress on the heart, its role is limited to improving the strength of the heartbeat.  The drug significantly decreased systolic blood pressure compared to placebo but it failed to improve relaxation of the heart between beats. A worrying number of adverse events were reported.

Other treatment strategies which combine drugs with physical activity may be the way forward for managing patients with permanent atrial fibrillation. Given the diagnosis of the patients studied, it is critical to compare the effects of spironolactone versus placebo on skeletal muscle oxygen utilisation, since it is a key determinant of exercise tolerance.

This is a relatively small study, and a large-scale study is not necessary due to the risks involved. A meta-analysis pooling data from similar studies is warranted to provide a robust understanding of the research question and findings.

Nduka Okwose, Research Associate, Faculty of Medical Sciences, University of Newcastle 

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