Ranolazine may ease right heart disease in precapillary PH: Study

RVEF increased by an average of 7.6% among patients who received treatment

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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An illustration showing a heart in front of a pair of lungs.

People with precapillary pulmonary hypertension (PH) and a poorly working right ventricle may benefit from ranolazine, which is used for chest pain caused by heart disease.

Data from a Phase 4 study where PH patients took ranolazine for about six months showed better right heart function and more sugar uptake, a measure of how much energy the heart’s muscle cells can produce, over a placebo.

The study, “Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: insights from a longitudinal, randomized, double-blinded, placebo controlled, multicenter study,” was published in Frontiers in Cardiovascular Medicine.

PH is high blood pressure in the blood vessels that supply the lungs. Because the vessels become stiff and can’t expand well, the heart’s right ventricle, or lower right chamber, must work harder to pump blood to the lungs. Over time, it becomes weaker.

Pulmonary vascular remodeling occurs when abnormal blood vessel repair causes them to become too thick and to resist the passage of blood. When this results in high blood pressure in the blood vessels that supply the lungs, it’s called precapillary PH.

Calcium ions enter the heart’s muscle cells with each heartbeat to help them contract. Ranolazine, sold under the name Ranexa among others, is thought to reduce the flow of calcium into the muscle cells, helping the heart relax.

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Ranolazine’s effect on precapillary PH

The medication is approved for angina —  chest pain caused by low blood flow to the heart — when other medicines have failed to work or can’t be taken. Earlier research suggested it might be able to be repurposed for pulmonary arterial hypertension (PAH), leading researchers in the U.S. to compare it against a placebo in a Phase 4 study (NCT01839110 and NCT02829034).

To enter the study, patients had to have a right ventricle ejection fraction (RVEF), a measure of the amount of blood pumped out of the right ventricle, of less than 45%. During screening, the patients were randomly assigned to ranolazine or a placebo.

Ranolazine was given by mouth at 500 mg twice daily for two weeks and then increased to 1,000 mg twice daily for 24 weeks (about six months). At the end of the treatment period, the researchers checked for changes in the RVEF.

Of the 22 patients in the study, 14 were assigned to the ranolazine group and eight to a placebo. Their mean age was similar (55.4 vs. 53.6) and about the same proportion had idiopathic PAH (64.3% vs 62.5%), or PAH without an identified cause. Fifteen completed the study.

At the end of treatment, the RVEF was significantly higher in the ranolazine group over the placebo group (39.6% vs. 22.5%), increasing by an average of 7.6%.

A positron emission tomography (PET) is a procedure wherein a small amount of radioactive glucose (sugar) is injected into a vein and a scanner makes pictures of the areas in the body where the glucose is taken up, allowing it to detect metabolic activity in cells.

Using a PET, it was found that more glucose was taken up by the heart muscle cells of patients in the ranolazine group than the placebo group. This finding suggests “ranolazine may improve RV [right ventricular] function by altering RV metabolism in patients with precapillary PH ,” the researchers wrote.

Because the study included only a small number of patients, larger studies “are needed to validate the beneficial effects of ranolazine,” they said. The study was funded in part by Gilead Sciences, which marketed Ranexa until it was discontinued.

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