Comparison of the pharmacodynamic effects of ranolazine versus amlodipine on platelet reactivity in stable patients with coronary artery disease treated with dual antiplatelet therapy

Amlodipine, commonly used for relief of ischemic symptoms in coronary artery disease (CAD), may affect clopidogrel-induced antiplatelet effects. It remains unknown if ranolazine, an antianginal drug that constitutes a pharmacologic alternative to calcium channel blockade, interferes with clopidogrel-induced antiplatelet effects. The aim of the ROMAN study was to compare the pharmacodynamic effects of ranolazine versus amlodipine on platelet reactivity in clopidogrel treated patients with CAD. A prospective, randomized, cross-over, open-label study conducted in a total of 210 CAD patients on aspirin (100 mg/q.d.) and clopidogrel (75 mg/q.d.) 1 month following percutaneous coronary intervention. Patients were randomly assigned to amlodipine (10 mg p.d., n = 105) or ranolazine (750 mg b.i.d., n = 105) for 15 days, and after a 1-week wash-out period, crossed-over treatment for 15 days. P2Y(12) reaction units (PRU) were assessed at baseline and after each treatment sequence. High on-treatment platelet reactivity (HPR) was defined as a PRU > 208. Amlodipine was associated with higher PRU than ranolazine (182 +/- A 75 vs. 167 +/- A 64, p = 0.028). As compared with baseline, PRU increased significantly after treatment with amlodipine (p = 0.018), but was not different after ranolazine therapy (p = 0.871). Changes in platelet reactivity following amlodipine therapy appeared to depend on baseline HPR status, as PRU levels significantly increased only among HPR subjects. In stable CAD patients treated with dual antiplatelet therapy after PCI, concomitant treatment with amlodipine, but not ranolazine, interferes with clopidogrel-induced antiplatelet effects.