Modifying Clopidogrel Maintenance Doses According to Vasodilator-Stimulated Phosphoprotein Phosphorylation Index Improves Clinical Outcome in Patients With Clopidogrel Resistance

Background: Despite dual antiplatelet therapy, the rate of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) remains high. Ex vivo tests of clopidogrel resistance can predict MACE after PCI. The purpose of this study is to evaluate the clinical impact of adjusting phosphorylation analysis in patients with clopidogrel resistance undergoing PCI. Hypothesis: We hypothesized that VASP-guided clopidogrel maintenance doses, compared to fixed doses, improved clinical outcome. Methods: This monocentric, prospective, randomized study was performed on 306 patients undergoing PCI. Patients were randomized to a control group (n = 156) and to a vasodilator-stimulated phosphoprotein (VASP)-guided group (n = 150). In the VASP-guided group, patients received adjusted maintenance doses of clopidogrel to obtain platelet reactivity index (PRI) of <50% during 1 year after PCI. The primary endpoint was the rate of MACE. The secondary endpoints were major and minor bleeding. Results: All patients completed the PCI procedure and 298 patients completed follow-up. The control and VASP-guided groups had similar demographic, clinical, and angiographic characteristics. In the VASP-guided group, PRI was significantly decreased (from 72.1% +/- 11.4% to 27.7% +/- 8.4%; P = 0.001) in 128 patients (87.1% of all participants). During the 1-year follow-up, 14 MACEs were recorded in the VASP-guided group and 30 MACEs were recorded in the control group (9.3% vs 20.4%, respectively; P = 0.008). There was no difference in the rate of major and minor bleeding in the VASP-guided group compared with the control group (12.9% vs 16.6%; P = 0.06). Conclusions: Modifying clopidogrel maintenance doses according to platelet reactivity monitoring decreases the rate of MACE after PCI without increasing bleeding in patients with clopidogrel resistance during 1-year follow-up.