Improvement of Doppler Derived Coronary Flow Reserve in Asymptomatic Patients with Previous Percutaneous Coronary Intervention on Left Anterior Descending Coronary Artery: Effects of Ranolazine

Background: Ranolazine reduces the Na-dependent calcium overload via inhibition of the late sodium current, improving diastolic tone and oxygen handling. In patients with previous percutaneous coronary intervention (PCI), microvascular coronary dysfunction can be still present. Transthoracic Doppler-derived coronary flow reserve (CFR) is an index of coronary arterial reactivity and decreases under the condition with microvascular dysfunction as well as coronary artery stenosis. The aim of this study was to assess the effect of ranolazine on CFR in this patient group. Methods: 48 asymptomatic patients (33 M, 15 F; mean age 66±11 years) with previous PCI on left anterior descending coronary artery (LAD) and no other significant coronary stenosis, was enrolled in the study. Within six weeks after PCI, they underwent baseline CFR assessment. Then they were randomly assigned to placebo or Ranolazine for 12 weeks (up-titrated from 350 to 750 mg twice, with increases every 4 weeks). CFR assessment was performed again at the end of treatment period. Coronary flow was assessed in the left anterior descending coronary artery (LAD), and was identified as the color signal directed from the base to the apex of the left ventricle, containing the characteristic biphasic pulsed-Doppler flow signals. CFR were determined as the ratio of hyperemic, induced by intravenous dypiridamole administration, to baseline diastolic coronary flow velocity. Results: There were no significant differences in baseline characteristics between Ranolazine and placebo group. CFR was successfully performed in all patients. Baseline CFR was not significantly different in Ranolazine and placebo group (2.23±0.59 vs. 2.19±0.55 - p = ns). After 12 weeks CFR significantly increased in Ranolazine group (2.65±0.64 vs. 2.23±0.59 - p < 0.01) but not in placebo group (2.24±0.58 vs. 2.19±0.55 - p = ns). No patient dropped out during 12 weeks therapy. Side effects were sinilar in both groups. Conclusions: In asymptomatic patients with previous PCI on LAD coronary artery Ranolazine is able to improve CFR. This is probably due to improvement in microvascular coronary dysfunction. Larger studies will be able to confirm these data.