Ranolazine Improves Right Ventricular Function in Patients With Precapillary Pulmonary Hypertension: Results From a Double-Blind, Randomized, Placebo-Controlled Trial

Introduction: A major outcome determinant in patients with precapillary pulmonary hypertension (PH) is right ventricular (RV) function. We studied the effect of ranolazine on RV function over 6 months using cardiovascular magnetic resonance (CMR) imaging in patients with precapillary PH (groups I, III, and IV).

Methods and results: We enrolled patients with PH and RV dysfunction (CMR imaging ejection fraction [EF] of <45%) in a longitudinal, randomized, double-blinded, placebo controlled, multicenter study of ranolazine treatment. All enrolled patients were on stable PH-specific therapy. Enrolled patients were assessed using CMR imaging, New York Heart Association functional class, N-terminal pro brain natriuretic peptide, 6-minute walk test, and quality of life health outcomes at baseline and repeated at the end of treatment. The primary outcome was change in RVEF after 6 months of treatment. Analysis of covariance was used to analyze the longitudinal changes taking into account baseline values, age, and sex, based on per protocol population. Twenty-two patients were enrolled, and 9 patients completed follow-up CMR imaging after ranolazine treatment and 6 completed placebo treatment. There was significant increase in RVEF at end of treatment compared with baseline in the ranolazine group adjusted for baseline values, age, and sex. There were no statistically significant changes in secondary outcomes such as changes in New York Heart Association functional class, 6-minute walk distance, N-terminal pro brain natriuretic peptide, or quality of life measures. Ranolazine treated patients experienced a higher number of adverse events, but only one was discontinued owing to side effects.

Conclusions: Ranolazine may improve RV function in patients with precapillary PH. Larger studies are needed to confirm the beneficial effects of ranolazine.