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

Abstract

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.

Platelet‐reactivity tests identify patients at risk of secondary cardiovascular events: a systematic review and meta‐analysis

“…An increased clopidogrel dose reduced the numbers of early and late CVEs in VASP-assay-defined HCPR patients undergoing non-emergent PCI [54][55][56]. In contrast, an increased clopidogrel dose did not reduce the number of major adverse CVEs in VerifyNow-defined HCPR patients who had undergone non-emergent PCI [57]. In patients undergoing elective PCI with HCPR according to LTA ADP 10 [58] or VerifyNow [46], the addition of a GPIIb-IIIa inhibitor peri-PCI reduced CVE incidence at 1 month of follow-up.…”

Benefits of laboratory personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials

“…Among them, 14 studies [11][12][13][14][15][16][17][18][19][20][21][22][23][24] reporting the differences in terms of MACEs and bleeding events between 9497 patients with and without the PAPT were considered eligible for our meta-analysis (4878 randomized to PAPT and 4619 to control) (Fig. 1).…”

Role of phenotypic and genetic testing in managing clopidogrel therapy

“…[60][61][62][63][64][65][66] Although poor responders to clopidogrel who were treated with an alternative P2Y12 inhibitor had improvement in clinical outcome, 67 these studies do not inform on whether routine biomarker testing and treatment intensification in poor responders were responsible for the improved outcome.…”