Optimal Anti-platelet Treatment For Patients With Clopidogrel Low Response:a Prospective Randomized Controlled Study

Objectives:To evaluate the efficacy and safety of intensive anti-platelet therapy for the patients with coronary heart disease who have been defined as clopidogrel low response (CLR) after percutaneous coronary intervention (PCI).Methods:This study was a prospective, single-center, randomized controlled study. The Light Transmittance Aggregometry (LTA) was used to find the clopidogrel low responders using a cutoff level of Adenosine Diphosphate Induced Platelet Aggregation (PLADP)>40%. From March 2014 to March 2015, a total of 180 CLR patients with coronary artery disease after percutaneous coronary intervention who meet the inclusion criteria were enrolled from Department of Cardiology in the First Affiliated Hospital of Nanjing Medical University. The selected patients were randomly divided into three groups:the patients in the group A (n=60) received aspirin 100mg/d and clopidogrel 75mg/d for 1 year, the patients in the group 2 (n=60) received aspirin 100mg/d and clopidogrel 150mg/d, after 30 days clopidogrel maintenance dose was switch to 75 mg/d and lasted for 1 years, the patients in the group 3 (n=60) received ticagrelor 75mg twice a day for one month, then switch to clopidogrel 75 mg/d until one year after PCI. All the three groups were followed up at the first months, sixth months and one year after PCI. All patients received PLADP test and biochemical examination at the first month follow-up. The major adverse events were major ischemic events, defined as a composite of cardiac death, nonfatal myocardial infarction and ischemic stroke. Secondary adverse events included stent thrombosis, target vessel revascularization (TVR) and cardiac rehospitalization. Safety events were TIMI bleeding events and other adverse reactions.Results:There were 59 patients in the group A,59 patients in the group B and 58 patients in the group C finished the whole study. The clinical data, biochemical indexes at hospitalization and the characteristics of angiography and percutaneous coronary intervention were not significantly different (P>0.05) between the three groups. Also the level of PLADP at the baseline was not significantly different (P=0.501). At the first month follow-up, the level of PLADP in the three groups was significantly different (P＜0.001), the level of PLADP at the first month follow-up in three groups were significantly lower than it at the baseline (P＜0.001). The level of PLADP in the Group C had a significantly reduction compared with the Groups A and B (P＜0.001), and the level of PLADP in the Group B also had a significantly reduction compared with the Group A (P=0.001). At follow-up, the rate of PLADP< 40% in the Group A, B and C were 42.5%,87.8% and 94.7%. There was significantly difference between the three groups (P＜0.001). The level of arachidonic acid induced platelet aggregation (PLAA) at the baseline was not significantly different (P=0.533). The level of PLAA at the first month follow-up was also not significantly different (P=0.182). Compared with the level of PLAA at the baseline, the level of PLAA at follow-up was not significantly different in both three group (P>0.05). The rate of major adverse events at one-year follow-up in the Group A, B and C were 8.6% (5/58),5.2%(3/58)和1.8%(1/57), there were no significant difference between the three groups (P=0.253). The rate of stent thrombosis (3.4% vs.3.4% vs.0%) and TVR (5.2% vs.3.4% vs.3.5%) were not significant difference between the three groups (P>0.05). The rate of cardiac hospital readmission in the three group was significant difference (36.2% vs.10.3% vs.8.8%, P＜0.001). The incidence of the major, minor bleeding was no significant difference between three groups (P>0.05). But the incidence of minimal bleeding was significantly different between three group (6.9% vs.15.5% vs.26.3%, P=0.003). The Group C has a higher rate of dyspnea compared with the other groups (P=0.003).Conclusion:Compare with the conventional clopidogel plus aspirin dual antiplatelet treatment, intensive antiplatelet treatment with double maintenance clopidogel or switch to ticagrelor is effective in reducing residual platelet aggregation, decreasing incidences of cardiac hospital readmission, without additional risk of major and minor bleeding in patients undergoing PCI.