Platelet Reactivity After Clopidogrel Administration on Drug-Eluting Stent
Platelet Reactivity After Clopidogrel Administration on Drug-Eluting Stent
Objectives: We sought to determine whether nonresponsiveness to clopidogrel as revealed by high in vitro post-treatment platelet reactivity is predictive of drug-eluting stent (DES) thrombosis.
Background: No data exist about the impact of nonresponsiveness to clopidogrel on the risk of DES thrombosis.
Methods: We conducted a prospective observational cohort study from July 2005 to August 2006 in an academic hospital. A total of 804 patients who had successful sirolimus- or paclitaxel-eluting stent implantation were assessed for post-treatment platelet reactivity after a loading dose of 600 mg of clopidogrel. Patients with platelet aggregation by 10 μmol adenosine 5'-diphosphate ≥70% were defined as nonresponders. All patients received chronic dual antiplatelet treatment (aspirin 325 mg and clopidogrel 75 mg daily) for 6 months. The primary end point was the incidence of definite/probable early, subacute, and late stent thrombosis at 6-month follow-up.
Results: The incidence of 6-month definite/probable stent thrombosis was 3.1%. All stent thromboses were subacute or late. Of 804 patients, 105 (13%) were not responsive to clopidogrel. The incidence of stent thrombosis was 8.6% in nonresponders and 2.3% in responders (p < 0.001). By multivariate analysis, the predictors of stent thrombosis were as follows: nonresponsiveness to clopidogrel (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.32 to 7.16; p = 0.009), left ventricular ejection fraction (HR 0.95, 95% CI 0.92 to 0.98; p = 0.001), total stent length (HR 1.01, 95% CI 1.00 to 1.02; p = 0.010), and ST-segment elevation acute myocardial infarction (HR 2.41, 95% CI 1.04 to 5.63; p = 0.041).
Conclusions: Nonresponsiveness to clopidogrel is a strong independent predictor of stent thrombosis in patients receiving sirolimus- or paclitaxel-eluting stents.
A dual antiplatelet regimen of aspirin and clopidogrel is the standard treatment for the prevention of stent thrombosis, and retrospective studies have shown that the discontinuation of clopidogrel, even after 6 months or later after stent implantation, is associated with an increased risk of thrombotic events in patients with drug-eluting stents (DES). However, stent thrombosis also can occur in patients taking clopidogrel and aspirin, and it has been shown that patients who suffer stent thrombosis have a high in vitro post-treatment platelet reactivity despite the dual antiplatelet treatment, suggesting that platelet aggregation nonresponsiveness to clopidogrel is the main cause of the thrombotic event. The definite demonstration of the association between low in vitro responsiveness to clopidogrel and thrombotic events is still lacking because the large majority of previous studies were retrospective or underpowered. Moreover, post-treatment platelet reactivity may interact with 1 or more established clinical and procedural predictors of stent thrombosis, making it difficult to define its role in precipitating thrombosis. In addition, studies have used different platelet reactivity assessments and definitions for determining the platelet responsiveness to clopidogrel. This prospective study sought to determine the impact of low responsiveness to clopidogrel on the clinical outcome of patients receiving DES.
Objectives: We sought to determine whether nonresponsiveness to clopidogrel as revealed by high in vitro post-treatment platelet reactivity is predictive of drug-eluting stent (DES) thrombosis.
Background: No data exist about the impact of nonresponsiveness to clopidogrel on the risk of DES thrombosis.
Methods: We conducted a prospective observational cohort study from July 2005 to August 2006 in an academic hospital. A total of 804 patients who had successful sirolimus- or paclitaxel-eluting stent implantation were assessed for post-treatment platelet reactivity after a loading dose of 600 mg of clopidogrel. Patients with platelet aggregation by 10 μmol adenosine 5'-diphosphate ≥70% were defined as nonresponders. All patients received chronic dual antiplatelet treatment (aspirin 325 mg and clopidogrel 75 mg daily) for 6 months. The primary end point was the incidence of definite/probable early, subacute, and late stent thrombosis at 6-month follow-up.
Results: The incidence of 6-month definite/probable stent thrombosis was 3.1%. All stent thromboses were subacute or late. Of 804 patients, 105 (13%) were not responsive to clopidogrel. The incidence of stent thrombosis was 8.6% in nonresponders and 2.3% in responders (p < 0.001). By multivariate analysis, the predictors of stent thrombosis were as follows: nonresponsiveness to clopidogrel (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.32 to 7.16; p = 0.009), left ventricular ejection fraction (HR 0.95, 95% CI 0.92 to 0.98; p = 0.001), total stent length (HR 1.01, 95% CI 1.00 to 1.02; p = 0.010), and ST-segment elevation acute myocardial infarction (HR 2.41, 95% CI 1.04 to 5.63; p = 0.041).
Conclusions: Nonresponsiveness to clopidogrel is a strong independent predictor of stent thrombosis in patients receiving sirolimus- or paclitaxel-eluting stents.
A dual antiplatelet regimen of aspirin and clopidogrel is the standard treatment for the prevention of stent thrombosis, and retrospective studies have shown that the discontinuation of clopidogrel, even after 6 months or later after stent implantation, is associated with an increased risk of thrombotic events in patients with drug-eluting stents (DES). However, stent thrombosis also can occur in patients taking clopidogrel and aspirin, and it has been shown that patients who suffer stent thrombosis have a high in vitro post-treatment platelet reactivity despite the dual antiplatelet treatment, suggesting that platelet aggregation nonresponsiveness to clopidogrel is the main cause of the thrombotic event. The definite demonstration of the association between low in vitro responsiveness to clopidogrel and thrombotic events is still lacking because the large majority of previous studies were retrospective or underpowered. Moreover, post-treatment platelet reactivity may interact with 1 or more established clinical and procedural predictors of stent thrombosis, making it difficult to define its role in precipitating thrombosis. In addition, studies have used different platelet reactivity assessments and definitions for determining the platelet responsiveness to clopidogrel. This prospective study sought to determine the impact of low responsiveness to clopidogrel on the clinical outcome of patients receiving DES.
