title: Comparison of antiplatelet efficacy and tolerability of clopidogrel napadisilate with clopidogrel bisulfate in coronary artery disease patients after percutaneous coronary intervention: a prospective, multicenter, randomized, open-label, phase IV, noninferiority trial.
abstract: BACKGROUND
  Clopidogrel bisulfate, a potent antiplatelet agent, has a pivotal role in the prevention and treatment of atherothrombotic disease. Clopidogrel napadisilate, a different salt preparation of clopidogrel, has been developed and approved in Korea and several European countries. Recent studies have suggested that clopidogrel napadisilate might have improved stability and comparable bioequivalence to clopidogrel bisulfate. However, these 2 clopidogrel preparations have not been compared in terms of efficacy and tolerability in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI).
  
  
  OBJECTIVE
  We sought to investigate the antiplatelet efficacy and safety profile of clopidogrel napadisilate compared with clopidogrel bisulfate in CAD patients after PCI.
  
  
  METHODS
  This was a randomized, multicenter, open-label, Phase IV, noninferiority clinical trial. We prospectively recruited CAD patient in 6 institutions in Korea between October 2010 and November 2011. Patients who underwent PCI were randomly assigned to the test group (clopidogrel napadisilate plus aspirin) or control group (clopidogrel bisulfate plus aspirin). Antiplatelet efficacy and safety profile were assessed after 4 weeks of maintenance treatment. The primary end point was noninferiority of the percentage of P2Y(12) inhibition, measured by point-of-care assay. The rate of major adverse cardiovascular events (MACE), as a secondary end point, was compared between the 2 clopidogrel preparations. To assess tolerability, we evaluated the incidence, severity, and causal relation of adverse events (AEs) of 2 groups.
  
  
  RESULTS
  A total of 169 patients were screened, and 127 patients completed the study (64 in the test group and 63 in the control group; P = 0.296). The baseline characteristics of patients did not differ significantly between the treatment groups. The between-group difference in percentage of P2Y(12) inhibition did not exceed the prespecified limit for noninferiority (P for noninferiority = 0.032; 95% CI, -8.33 to 5.53). With respect to the risk of MACE, no significant difference was found in the incidence of myocardial infarction or stroke between the groups (1 in the test group and 2 in the control group; P > 0.99); no mortality was reported in either group. The tolerability of clopidogrel napadisilate was comparable with that of clopidogrel bisulfate in terms of all AEs, drug-related AEs, and serious AEs (all AEs: test group, 33.3%; control group, 32.9% [P > 0.99]; drug-related AEs: test group, 4.17%; control group, 0% [P = 0.113]; serious AEs: test group, 1.39%; control group, 5.26% [P=0.367]).
  
  
  CONCLUSIONS
  In this study of CAD Korean patients who have undergone PCI, the antiplatelet efficacy of clopidogrel napadisilate was noninferior to that of clopidogrel bisulfate after 4 weeks of maintenance treatment. No statistically significant difference was found in tolerability between the 2 treatment groups.
authors: Division of Cardiology, Department of Internal Medicine/Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.
authors: Jun-Bean
authors: JB
authors: Park
authors: Bon-Kwon
authors: BK
authors: Koo
authors: Woong-Gil
authors: WG
authors: Choi
authors: Seok-Yeon
authors: SY
authors: Kim
authors: Jinsik
authors: J
authors: Park
authors: Jun
authors: J
authors: Kwan
authors: Chang Gyu
authors: CG
authors: Park
authors: Hyo-Soo
authors: HS
authors: Kim
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000401:mortality / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000401:mortality; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D019095:Point-of-Care Systems; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects / Q000378:metabolism; D056910:Republic of Korea; D013810:Therapeutic Equivalency; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine