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

The ROMAN (RanOlazine vs. aMlodipine on platelet reactivity in stable patients with CAD treated with dual ANtiplatelet therapy) study

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Abstract

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. P2Y12 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 ± 75 vs. 167 ± 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.

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Conflict of interest

Francesco Pelliccia, Cesare Greco, Carlo Gaudio, Giuseppe Rosano, Cristiana Vitale, Giuseppe Marazzi, Fabiana Rollini have no conflict of interest to report. Dominick J. Angiolillo: Received payment as an individual for: (a) Consulting fee or honorarium from Bristol-Myers Squibb, Sanofi-Aventis, Bayer, Eli Lilly, Daiichi Sankyo, Inc., The Medicines Company, AstraZeneca, Merck, Abbott Vascular, and PLx Pharma; (b) Participation in review activities from CeloNova, Johnson & Johnson, St. Jude, and Sunovion. Has received institutional payments for grants from Bristol-Myers Squibb, Sanofi-Aventis, GlaxoSmith Kline, Eli Lilly, Daiichi Sankyo, Inc., The Medicines Company, AstraZeneca, Gilead.

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Authors and Affiliations

  1. Department of Cardiovascular Sciences, Sapienza University, Via Tommaso Inghirami 85, 00179, Rome, Italy

    Francesco Pelliccia MD, PhD, Cesare Greco & Carlo Gaudio

  2. IRCCS San Raffaele Pisana, Rome, Italy

    Giuseppe Rosano, Cristiana Vitale & Giuseppe Marazzi

  3. Division of Cardiology, Department of Medicine, University of Florida College of Medicine, Jacksonville, FL, USA

    Fabiana Rollini & Dominick J. Angiolillo

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  1. Francesco Pelliccia MD, PhD
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  2. Cesare Greco
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  3. Carlo Gaudio
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  4. Giuseppe Rosano
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  5. Cristiana Vitale
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  6. Giuseppe Marazzi
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  8. Dominick J. Angiolillo
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Correspondence to Francesco Pelliccia MD, PhD.

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ClinicalTrials.gov Identifier: NCT01490255.

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Pelliccia, F., Greco, C., Gaudio, C. et al. Comparison of the pharmacodynamic effects of ranolazine versus amlodipine on platelet reactivity in stable patients with coronary artery disease treated with dual antiplatelet therapy. J Thromb Thrombolysis 40, 331–339 (2015). https://doi.org/10.1007/s11239-015-1203-9

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  • DOI: https://doi.org/10.1007/s11239-015-1203-9

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