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
What are the effects of high versus standard clopidogrel maintenance doses on platelet inhibition, inflammation, and endothelial function in patients undergoing percutaneous coronary intervention?
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 P2Y12 reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, CA]), endothelial function (evaluated by flow-mediated vasodilation), and high-sensitivity C-reactive protein levels were measured at T-0, T-1, and T-2.
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 a decreased proportion of patients with P2Y12 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).
The authors concluded that 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.
This study suggests that, compared with the standard 75 mg daily dose, use of a 150 mg/day clopidogrel maintenance regimen is associated with a higher degree of platelet inhibition and reduction of low-responders, as well as with significant improvement of endothelial function and enhanced anti-inflammatory effects. There was no benefit on cardiovascular clinical outcomes or stent thrombosis with a double dose of clopidogrel (150 mg/day) in patients receiving stents with high residual platelet activity on the regular clopidogrel dose in the large GRAVITAS trial. A regimen of 150 mg/day does not appear to be more effective clinically and is not recommended at this time.
Clinical Topics: Invasive Cardiovascular Angiography and Intervention
Keywords: Inflammation, Platelet Aggregation Inhibitors, Ticlopidine, Blood Platelets, Angioplasty, Purinergic P2Y Receptor Antagonists
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