Coronary artery disease
Tailored Clopidogrel Loading Dose According to Platelet Reactivity Monitoring to Prevent Acute and Subacute Stent Thrombosis

https://doi.org/10.1016/j.amjcard.2008.08.048Get rights and content

Stent thrombosis remains a significant pitfall of percutaneous coronary intervention (PCI). A recent trial observed that an adjusted loading dose (LD) of clopidogrel according to platelet monitoring decreases the rate of major adverse cardiovascular events after PCI. We investigated if such a strategy of a tailored clopidogrel LD according to platelet reactivity monitoring could decrease the rate of stent thrombosis. This multicenter prospective randomized study included 429 patients with a low clopidogrel response after a 600-mg LD undergoing PCI. Patients were randomized to a control group (n = 214) and to a vasodilator-stimulated phosphoprotein (VASP)-guided group (n = 215). In the VASP-guided group, patients received up to 3 additional 600-mg LDs of clopidogrel to obtain a VASP index <50% before PCI. The primary end point was the rate of stent thrombosis at 1 month. Secondary end points were rates of major adverse cardiovascular events and bleeding. Patients in the 2 groups had a high body mass index and were often diabetic (control vs VASP-guided group 28 ± 5.1 vs 27.9 ± 4.7 kg/m2, p = 0.8, and 39% vs 33%, p = 0.2, respectively). PCI was performed in most patients for acute coronary syndrome in the 2 groups (52.3% vs 50.7%, p = 0.8). Despite a 2,400-mg LD of clopidogrel, 8% of patients in the VASP-guided group remained low responders. The rate of stent thrombosis was significantly lower in the VASP-guided group (0.5% vs 4.2%, p <0.01). The rate of major adverse cardiovascular events was also higher in the control group (8.9% vs 0.5%, p <0.001). There was no difference in the rate of bleeding (2.8% vs 3.7%, p = 0.8). In conclusion, a tailored clopidogrel LD according to platelet reactivity monitoring decreases the rate of early stent thrombosis after PCI without increasing bleeding.

Section snippets

Methods

A multicenter, prospective, randomized study was performed. The study protocol was in accordance with the Declaration of Helsinki and approved by the local ethics committee of our institutions. All patients gave written informed consent before inclusion. Patients undergoing PCI for refractory angina pectoris under optimal medical therapy, silent ischemia on thallium scintigraphy, or non–ST-elevation acute coronary syndrome were eligible for inclusion. Exclusion criteria were persistent

Results

From August 2007 to March 2008, 1,122 patients admitted to the participating cardiology centers were prospectively screened for inclusion (Figure 1). A cohort of 953 patients without exclusion criteria was considered eligible. Because 55% of those patients had a VASP index <50% after the first LD of clopidogrel and therefore were considered good responders, they were not included in the study. A total of 429 patients had a VASP index ≥50% and were included and randomized to the control group (n

Discussion

The present study suggests that a tailored clopidogrel LD according to platelet reactivity monitoring decreases the rate of stent thrombosis in patients undergoing PCI. Of importance, this strategy of clopidogrel LD adjustment was safe and not associated with increased bleeding.

This result is of clinical interest because stent thrombosis still occurs at a relatively high rate and is a major clinical concern because of its poor prognosis.8, 9, 10, 11 Further, the benefit of a tailored LD of

Acknowledgment

We thank the catheterization laboratory staff and nurses for their assistance. We also thank Probal Roy, MD, Gilles Lemesle for their helpful comments and Kathryn Coons, medical writer, for her great editorial assistance in the preparation of this report.

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