| Background and Objectives Antiplatelet therapy significantly decreases the incidence of thrombotic events after coronary stenting. However, about 5%~35% of patients were associated with an increased risk of thrombotic events because of antiplatelet resistance. At present, there was no uniform diagnosis standard of antiplatelet resistance, as well as effective therapeutic methods. The present study was aimed to screen effective and convenient diagnosis measures of aniplatelet resistance, to analyze the relationship between antiplatelet resistance and clinical risk factors, and to explore the efficacy and safety of optimal anitplatelet therapy in managing antiplatelet resistance.Methods Between June 2006 and February 2007, a total of 305 patients who underwent coronary stenting were prospectively enrolled. Expression of platelet CD62P, platelet activated complex -1(PAC-1) and 20μmol/L ADP induced platelet aggregation (IPA) were assayed before and 24 h after administration of antiplatelet agents. An absolute reduction of IPA <10% compared with baseline was served as the golden standard of the diagnosis of clopidogrel resistance (CR). Enrolled patients were randomly assigned to receive optimal (optimal group, n=154) or standard antiplatelet therapy (standard group, n=151). The antiplatelet regimen of standard group was dual antiplatelet therapy with aspirin and clopidogrel. Antiplatelet therapy for the patients in optimal group depended on the results of IPA assay: patients with CR were received cilostazol for 6 months in addition to dual anitplatelet therapy, whereas non-CR patients received standard dual antiplatelet therapy. The primary endpoint was the composite of death, myocardial infarction (MI) and stroke at 1 year. The secondary end points was the composite of death, MI, ischemic driven revascularization, stroke and peripheral artery occlusions, TIMI hemorrhagic events, subacute and late stent thrombosis.Results (1) The incidence of CR was 23.8%. Recipient operation characteristic curve showed that CD62P and PAC-1 were not valuable in diagnosis of CR. However, post therapy IPA induced by 20μmol/L ADP was valuable for the diagnosis of CR with an area under curve of 0.878 and cutoff value of 71.8%. The sensitivity and specificity were 77.8% and 85.2%, respectively. (2) Multivariate analysis demonstrated that≥65 years old (OR=10.31, 95%CI= 4.265- 24.926, P<0.001), diabetes (OR=9.3, 95%CI= 3.413-25.344, P<0.001), history of ischemic events (OR=7.139, 95%CI= 2.658-19.180, P<0.001), positive TnT (OR=7.6, 95%CI=1.505-38.39, P=0.014) and multivessel disease (OR=2.355, 95%CI=1.054- 5.261, P=0.037) were predictors of CR. Two or more risk above mentioned risk factors strongly predicted CR (AUC 0.899, sensitivity of 86.5% and specificity of 79.7%). (3) Patients in optimal group were associated with a 37% reduction in the risk of primary events compared with their counterparts in standaardl group (5.8% vs. 9.3%, P=0.257). The rates of death (1.9% vs. 2.6%, P=0.489), M(I2.6% vs. 6%, P=0.340)and ischemic stroke(1.3% vs. 2.0,P=0.491)were not significantly different between the two groups. Optimal group was also associated with a tendency of decreased incidence of secondary end points [9.7%(15/154) vs. 14.6(22/151),P=0.197]. There was no difference in the rates of stent thrombosis and hemorrhagic events between the two groups. 41(26.6%)patients in the optimal group and 33(21.9%) in the standardl group were diagnosed as CR according to IPA assay. In CR patients, IPA were significantly reduced after cilostazol treatment [(77.5±12.1)% vs. (64.5±12.1)%,P<0.001]. CR patients in optimal group had a lower but not statistically significant incidence of primary events [19.5%(8/41)比36.4%(12/33), RR= 54%,95%CI:0.25-1.16, P=0.105].Conclusions IPA induced by 20μmol/L ADP after antiplatelet treatment is reasonable to be served as the diagnosis standard of CR. Clinical risk factors such as≥65 years old, diabetes, history of ischemic events, TnT positive and multivessel coronary artery disease are predictors of CR and the number of the risk factors are associated with the risk of CR. Adjusting antiplatelet regimen according to IPA assay results might be effective in improving long-term outcomes for patients undergoing coronary stenting, especially for those diagnosed as CR. However, the effectiveness and safety need further confirmation by clinical trials with large sample size. |
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