ABSTRACT
OBJECTIVES: We investigated the effect of ranolazine on endothelial-dependent vasodilatation (EDV), serum markers of endothelial dysfunction, and inflammation. BACKGROUND: Endothelial dysfunction has been shown to be independently associated with the occurrence of cardiovascular events. We sought to investigate whether ranolazine, a novel antianginal medication with no effect on heart rate or blood pressure, improves endothelial function in patients with stable coronary artery disease (CAD). METHODS: Twenty-seven patients with stable CAD were randomly assigned to either 1000 mg twice daily of ranolazine or to matching placebo for 6 weeks and then crossed over for an additional 6 weeks in a double-blind design. EDV was assessed using reactive hyperemia peripheral arterial tonometry (RH-PAT) at baseline, 6, and 12 weeks. Markers of endothelial dysfunction and inflammation were also evaluated. RESULTS: After 6 weeks, treatment with ranolazine significantly increased the EDV RH-PAT index as compared with baseline (1.85+/-0.42 vs. 2.08+/-0.57, P = 0.037). EDV RH-PAT did not change while on placebo (1.69+/-0.35 vs. 1.78+/-0.41, P = 0.29). In addition, there was a significant drop in asymmetric dimethylarginine levels with ranolazine treatment (0.66+/-0.12 vs. 0.60+/-0.11 micromol/l, P = 0.02) and a near significant decrease in C-reactive protein levels (0.40+/-0.80 vs. 0.30+/-0.61 mg/dl, P = 0.05). CONCLUSION: Ranolazine improves endothelial function, asymmetric dimethylarginine, and C-reactive protein levels in a group of patients with stable CAD. Our results suggest a novel mechanism of action of ranolazine.
