Effects of Trimetazidine on Right Ventricular Function and Ventricular Remodeling in Patients with Pulmonary Artery Hypertension: A Randomised Controlled Trial

Abstract

Background: Pulmonary artery hypertension (PAH) is a chronic and progressive disease. Although current therapy has improved the disease prognosis, PAH has a poor survival rate. The key feature leading to disease progression and death is right ventricular (RV) failure. Methods and results: We assessed the role of trimetazidine, a fatty acid beta-oxidation (FAO) inhibitor, in right ventricular function, remodeling, and functional class in PAH patients, with a placebo-controlled double-blind, case-crossover trial. Twenty-seven PAH subjects were enrolled, randomized, and assigned to trimetazidine or placebo for three months and then reallocated to the other study arm. The primary endpoint was RV morphology and function change after three months of treatment. Secondary endpoints were the change in exercise capacity assessed by a 6 min walk test after three months of treatment and the change in pro-BNP and Galectin-3 plasma levels after three months. Trimetazidine use was safe and well-tolerated. After three months of treatment, patients in the trimetazidine group showed a small but significant reduction of RV diastolic area, and a substantial increase in the 6 min walk distance (418 vs. 438 mt, p = 0.023), without significant changes in biomarkers. Conclusions: A short course of trimetazidine is safe and well-tolerated on PAH patients, and it is associated with significant increases in the 6MWT and minor but significant improvement in RV remodeling. The therapeutic potential of this drug should be evaluated in larger clinical trials.

Keywords

• pulmonary artery hypertension
• right ventricular failure
• trimetazidine
• fatty acid beta-oxidation inhibitor
• 6 min walk test
• pro-BNP