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Lung disease drug offers hope for heart failure patients heart-failure - Health Europa

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A drug currently used to treat lung fibrosis could be repurposed to treat heart failure patients, an early phase trial has suggested.

Doctors and scientists from the University of Manchester and Manchester University NHS Foundation Trust, in collaboration with Liverpool Clinical Trials Centre, trialled the drug pirfenidone and found that it could offer a viable treatment for heart failure with preserved ejection fraction (HFpEF).

The findings from the trial have been published in Nature Medicine.

Heart failure with preserved ejection fraction

Heart failure and its different types are based on a measurement called the ejection fraction, which determines how much blood inside the ventricle is pumped out with each contraction. The left ventricle squeezes and pumps some of the blood in the ventricle out to your body. HFpEF happens when the left ventricle is not filling with blood as well as normal. The ventricle can pump well, but it may be stiff so it cannot relax and properly fill with blood.

While a number of processes lead to heart failure, scarring – or fibrosis – of the heart muscle is thought to be an important mechanism in around up to two-thirds of patients with HFpEF and is associated with adverse outcomes.

Heart scarring

Dr Chris Miller, National Institute for Health Research Clinician Scientist at The University of Manchester and Consultant Cardiologist at Manchester University NHS Foundation Trust, led the study.

Dr Miller said: “Heart failure is as devastating an illness as some of the most common cancers, however its profile its much lower and treatment options for HFpEF are very limited.

“Using cardiac MRI, we were able to select patients in whom heart scarring is important. Pirfenidone then reduced that scarring.”

Pirfenidone works by inhibiting the biological processes involved in scar formation.

The study enrolled patients with heart failure, normal forward pumping function of the heart, and evidence of fluid retention. Eligible patients had cardiac MRI scanning, and those who had evidence of heart scarring, as indicated by a measurement called ‘extracellular volume’, were randomly assigned to take pirfenidone or a placebo daily. 94 patients were randomised, with 47 assigned to each treatment group.

After one year, patients had a second cardiac MRI to measure change in heart scarring. Extracellular volume declined by 1.21% on average in patients who took pirfenidone, compared with those receiving placebo.

“Based on data from previous studies, this amount of reduction in heart scarring could translate into a substantial reduction in rates of death and admission to hospital for heart failure, however larger trials are needed to determine this,” said Dr Miller.

Fluid retention, measured using a blood test called NT-proBNP, also improved in patients taking pirfenidone compared to those receiving placebo.

Dr Miller added: “Though further investigation is required, the associated improvement in fluid retention provides support for heart scarring having a causal role in heart failure and being an effective treatment target.”

The most common side effects of the drug were nausea, insomnia, and rash, which are similar to those experienced by lung patients when taking Pirfenidone.

Despite the significant findings from the study, the team said that larger-scale trials are needed before it can be licensed for use in the NHS.

Dr Miller said: “These findings are exciting and suggest that pirfenidone could benefit patients with this condition, however further trials are required.”

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