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

Study Questions:

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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