Treatment with Milrinone Improves Heart Function in Patients with PH Due to Left Heart Disease, Study Finds

Intravenous treatment with the approved heart failure medicine milrinone leads to significant improvements in heart structure and function in patients with mild-to-moderate pulmonary hypertension (PH) due to left heart disease, a study has found.”

The report titled “Study on the clinical efficacy of specific phosphodiesterase inhibitor in patients with pulmonary hypertension due to left heart disease” was published in the journal Experimental and Therapeutic Medicine.

Currently, there are no approved therapies for patients with PH due to left heart disease (PH-LHD). Despite the fact that several pulmonary arterial therapies have been investigated, none has proven effective for these patients.

Consequently, there is a need to “explore alternative drugs that are effective against PH‐LHD and to prove their effectiveness,” researchers wrote.

Milrinone, marketed under the brand name Primacor (among others), is a common treatment for heart failure, and it also has been suggested to have a therapeutic effect in PH.

Milrinone is an inhibitor of the phosphodiesterase 3 (PDE 3) enzyme, leading to improvements in the contraction of heart cells and promoting heart blood vessels’ dilation, causing better blood flow.

Researchers tested the use of milrinone in 60 patients with PH‐LHD, all receiving conventional treatment for heart failure. The research drug used in the study was milrinone injection, produced by Nonan Bate Pharmaceuticals in China.

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Participants were divided into three groups: groups A and B received milrinone intravenously (directly into the bloodstream) for 10 minutes at a rate of 5 microgram/kg/min, followed by a maintenance dose (administered continuously for five days) as 0.25 (group A) and 0.5 microgram/kg/min (group B). Group C was the control group in which patients received no milrinone.

Patients were given an echocardiograph, a ultrasound scan that looks into the heart and nearby blood vessels, before and after treatment with milrinone. Blood samples also were retrieved and analyzed.

Results showed that treatment with milrinone significantly reduced PH‐LHD patients’ pulmonary artery systolic pressure (PASP), while no effects were seen in patients treated with conventional therapies alone.

Moreover, at a dose of 0.5 microgram/kg/min, milrinone showed superior efficacy and significantly improved the heart’s left ventricle structure and function of patients with mild-to-moderate PH-LHD.

Milrinone also led to a significant improvement of the right heart function in PH-LHD patients compared with conventional treatment.

Because the pool of participants included only two patients with severe PH‐LHD in groups A and group B, researchers could not assess the therapy’s effectiveness in this specific group.

The 2015 PH guidelines of the European Heart Association recommend measuring the levels of brain natriuretic peptide (BNP), a hormone that is released by the heart in cases of heart failure, as the only biomarker for risk of PAH.

Treatment with milrinone significantly reduced the levels of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and that of the hypersensitive C-reactive protein — a well-known marker of inflammation and tissue damage and a risk factor for heart disease — in patients with PH‐LHD.

The maintenance dose of milrinone did not cause any significant adverse reactions during the course of the treatment.

Overall, these results suggest that “a small dose of milrinone may significantly reduce PASP in patients with mild and moderate PH‐LHD, and significantly improve the cardiac structure, cardiac function and biochemical indexes,” researchers wrote.

“In future studies, the milrinone maintenance dose may be increased within the specified dose range, to see if heart function and structure, PASP and test indicators of patients with PH-LHD may be improved, and whether adverse events increase with higher doses,” they added.