Modest gain from milrinone in HFpEF pilot study

Heart failure

By Mardi Chapman

2 Jul 2020

The inotropic and vasodilator drug milrinone, in an extended-release oral formulation, appears to improve quality of life and be well tolerated in patients with HFpEF, Australian research shows.

A pilot study at the Alfred Hospital randomised 23 patients with symptomatic HFpEF to either the phosphodiesterase type III (PDE3) inhibitor or placebo.

Predominantly a safety study, the investigators found no significant changes in heart rate or blood pressure and no atrial or ventricular arrhythmias. The only serious adverse event, a hospitalisation for heart failure, occurred in the control group.

The study also found patients treated with milrinone had a greater improvement in quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), than controls (+10±13 v −3±15; P=0.04).

Treatment was also associated with a non-significant trend towards improvement in the 6MWD (10±62 versus −42±77; P=0.092).

Echocardiography revealed no significant between-group differences in the change in early filling velocity /early mitral annular velocity and no other changes in cardiac structure or function.

Lead investigator Dr Shane Nanayakkara, a cardiologist at the Alfred and a research fellow at the Baker Heart and Diabetes Institute, told the limbic that the improvement in quality of life was probably real despite the small size of the study.

“From a mechanistic point of view there are good reasons why milrinone would increase quality of life. Milrinone has a lot of different effects so in a disease which probably has lots of different subtypes, it could work in different ways.”

“Milrinone is one of the few drugs which is lusitropic and can help directly relax the heart muscle. It also lowers pressure in the lungs – a downstream consequence of HFpEF – and it is also a vasodilator.”

He said patients may have felt less short of breath or that they could be more active.

Dr Nanayakkara said early trials of milrinone in patients with HFrEF had shown some safety signals.

“But it was done in a very different type of patient, obviously a different type of heart failure to start with and in a time when we didn’t have other protective drugs around e.g. beta blockers,” he said.

“This was a very different trial because we gave much lower doses of milrinone and also gave a long acting version of milrinone rather than something which spikes and falls really quickly which increases the adverse effects.”

He said the oral formulation was currently only available in a research setting but there were now plans to collect more data in a larger RCT across multiple sites.

The study, published in the Journal of the American Heart Association, was funded by Cardiora and the NHMRC.

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