High Versus Standard Clopidogrel Maintenance Dose After Percutaneous Coronary Intervention and Effects on Platelet Inhibition, Endothelial Function, and Inflammation Results of the ARMYDA-150 mg (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty) Randomized Study

Objectives This study was done to compare effects of high versus standard clopidogrel maintenance doses on platelet inhibition, inflammation, and endothelial function in patients undergoing percutaneous coronary intervention. Background Previous data suggested that clopidogrel has various biological actions in addition to antiplatelet effects. Methods Fifty patients were randomly assigned 1 month after intervention (T-0) to receive standard (75 mg/day; n = 25) or high (150 mg/day; n = 25) clopidogrel maintenance dose for 30 days (until T-1); at this time-point, cross-over was performed, and the assigned clopidogrel maintenance regimen was switched and continued for a further 30 days (until T-2). Platelet reactivity (expressed as P2Y(12) reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]), endothelial function (evaluated by flow-mediated vasodilation), and high-sensitivity C-reactive protein levels were measured at T-0, T-1, and T-2. Results Patients in the 150-mg/day arm had higher platelet inhibition (50 +/- 20% vs. 31 +/- 20% in the 75-mg/day group; p < 0.0001), better flow-mediated vasodilation (16.9 +/- 12.6% vs. 7.9 +/- 7.5%; p = 0.0001), and lower high-sensitivity C-reactive protein levels (3.6 +/- 3.0 mg/l vs. 7.0 +/- 8.6 mg/l; p = 0.016). Higher clopidogrel dose was associated with decreased proportion of patients with P2Y(12) reaction units >= 240 (12% vs. 32%; p = 0.001), flow-mediated vasodilation <7% (16% vs. 58%; p = 0.0003), and high-sensitivity C-reactive protein levels >3 mg/l (46% vs. 64%; p = 0.07). Conclusions For patients undergoing percutaneous coronary intervention, the 150-mg/day clopidogrel maintenance dose is associated with stronger platelet inhibition, improvement of endothelial function, and reduction of inflammation, compared with the currently recommended 75-mg/day regimen; those effects might have a role in the clinical benefit observed with clopidogrel and may provide the rationale for using the higher maintenance regimen in selected patients. (J Am Coll Cardiol 2011; 57: 771-8) (C) 2011 by the American College of Cardiology Foundation