A high maintenance dose increases the inhibitory response to clopidogrel in patients with high on-treatment residual platelet reactivity

Background: Patients with high on-treatment residual adenosine diphosphate-inducible platelet reactivity (HRPR) despite clopidogrel therapy are at an increased risk for adverse events after coronary stenting. A higher maintenance dose of clopidogrel may increase the inhibitory response in these patients.

Methods: We randomly assigned 46 patients with HRPR in at least one of three platelet reactivity tests to 75 mg vs. 150 mg clopidogrel for 3 months after angioplasty and stenting for cardiovascular disease. Platelet reactivity was assessed by the VerifyNow P2Y12 assay, the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, and multiple electrode aggregometry (MEA) 24h and 3 months after the intervention.

Results: Baseline platelet reactivity data did not differ significantly between treatment groups (all p > 0.2). At 3 months, platelet reactivities by the VerifyNow P2Y12 assay, the VASP assay, and MEA were 262 ± 74 P2Y12 reaction units (PRU), 59.5 ± 21.3%, and 46 ± 19 aggregation units (AU) in the standard dose group vs. 190 ± 78 PRU, 36.1 ± 16.8%, and 26 ± 16 AU in the high maintenance dose group (all p ≤ 0.003). Further, HRPR was significantly less frequent in patients assigned to 150 mg clopidogrel compared to patients receiving 75 mg clopidogrel per day (33% vs. 87%; p < 0.001).

Conclusion: A high maintenance dose increases the antiplatelet effects of clopidogrel in patients with HRPR after angioplasty and stenting for cardiovascular disease. However, it needs to be shown that the higher dosage is associated with a beneficial clinical outcome in these patients.