Prevention - ACHIEVE

The clinical question

Kidney failure is the stage of chronic kidney disease (CKD) when the kidneys can no longer filter waste products from the blood efficiently enough to keep the body healthy. People with kidney failure will usually have regular dialysis, a procedure to remove waste products and excess fluid from the blood. This is the usual treatment for people who are waiting for a kidney transplant, including those who may not be able to have a kidney transplant for other reasons.

The dialysis procedure helps to keep people with kidney failure alive, but those receiving dialysis are at high risk of heart failure and dying due to a heart-related cause. As of 2025, there are over 30,000 people in the UK receiving dialysis treatment - and this number is set to rise.

Spironolactone is a type of medication called a diuretic (or water tablet), which is used as a treatment for high blood pressure and heart failure. It works by blocking the effects of a hormone called aldosterone, which can cause high blood pressure and have damaging effects on the heart and blood vessels. Spironolactone can be an effective treatment for people with heart failure, helping to reduce hospitalisations and improve survival. Some previous research had suggested that spironolactone might also be beneficial for people receiving dialysis, but these studies were not large enough to be conclusive.

ACHIEVE was an international clinical trial designed to find out if spironolactone could help reduce heart failure and heart-related deaths in people on dialysis for kidney failure. The trial was led from Canada by Dr Michael Walsh at the Population Health Research Institute. BHF funded a team led by Professor Patrick Mark at the University of Glasgow, to enable the UK to be part of this important trial.

What did the study involve?

People receiving dialysis were eligible to be in the trial if they were over 45 years old (or over 18 if they had diabetes), had been receiving dialysis for at least 3 months and provided their consent to take part. Between September 2017 and October 2024, 3565 people receiving dialysis were enrolled across 143 dialysis programmes in 12 countries. In the UK, participants were enrolled from 23 dialysis centres across all 4 nations. About two-thirds of enrolled participants were men and a third were women, which matches the demographics of people receiving long term dialysis.

Spironolactone can have side effects including increasing levels of potassium in the blood, which can cause abnormal heart rhythms. People with kidney failure may be at higher risk of this happening, as they’re already more likely to have high blood potassium levels. ACHIEVE therefore had a ‘run in’ period, where participants were asked to take the drug for 7 weeks to see if they were safely able and willing to take it for the duration of the trial.

Following run in, 2538 participants were randomly assigned to two groups:

• Half were assigned to take a 25mg tablet of spironolactone each day.
• Half were assigned to take a placebo (dummy) tablet each day, containing no active ingredients.

Participants were followed up at 3 and 6 months after being randomised and then every 6 months, for an average of 1.8 years. The main aim was to see whether taking spironolactone had an effect on the risk of cardiovascular events - defined as dying due to a heart-related cause or needing to be hospitalised due to heart failure.

What did the study show?

• There was no significant difference in cardiovascular events between people who took spironolactone and those who took placebo tablets. 258 participants in the spironolactone group experienced a cardiovascular event, compared to 276 in the placebo group.
• People who received spironolactone were more likely to have severely high blood potassium levels.
• The researchers also looked at whether there was any difference in the effect of spironolactone between male and female participants. This suggested that possibly male participants benefitted from taking spironolactone, while female participants didn’t - but this was an inconclusive finding, which needs further research to be certain if it’s true.

Why is the study important?

Overall, ACHIEVE does not support the use of spironolactone in people receiving dialysis. Neutral findings in clinical trials are just as important as positive findings – they help ensure that people don’t receive treatments that won’t be beneficial for them, and highlight where research is needed to look for alternative options.

Summarising the results at the European Renal Association Congress in June 2025, lead investigator Dr Michael Walsh said: “We really hoped that spironolactone could make a difference for people on dialysis. While the results are not what we wanted, they provide much-needed clarity.”

Professor Patrick Mark, the UK lead for the trial, added: "Although the trial result was neutral, this is another crucial piece of information which will help the quest to improve outcomes for people with kidney failure treated with dialysis."

People receiving dialysis have often been excluded from previous research looking at how to reduce a person’s risk of cardiovascular events. ACHIEVE is the largest clinical trial to date testing whether a drug can benefit people receiving dialysis, that has been led by academic researchers rather than a pharmaceutical company. It has helped to create an international community of researchers who are ready to undertake clinical trials in this area, paving the way for future advances and improved outcomes for people on dialysis. Following ACHIEVE, the lead researchers have been awarded funding from the NIHR in the UK and the CIHR in Canada to carry out a new trial. The PHOSPHATE trial will test whether lowering blood phosphate levels can help to reduce cardiovascular events in people receiving dialysis.

The participant voice

John Mannion was one of the 368 UK participants in ACHIEVE. He took part in the study in Glasgow, the lead UK centre for the trial, and shared his perspective: “While the medicine tested in the trial might not have been beneficial, I had a good experience taking part. It was great to be part of a research study trying to prevent cardiovascular events in people on dialysis."

More research is needed to find out what medicines might help people like me. I hope that future trials can discover ways to reduce cardiovascular events in people on dialysis.

Study details

Publication details

Walsh M et al. Spironolactone versus placebo in patients undergoing maintenance dialysis (ACHIEVE): an international, parallel-group, randomised controlled trial. Lancet. August 2025.

Page first published: October 2025