PMID- 23328268 OWN - NLM STAT- MEDLINE DCOM- 20130702 LR - 20181202 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 35 IP - 1 DP - 2013 Jan TI - 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. PG - 28-37.e4 LID - S0149-2918(12)00670-4 [pii] LID - 10.1016/j.clinthera.2012.12.004 [doi] AB - 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. CI - Copyright (c) 2013 Elsevier HS Journals, Inc. All rights reserved. FAU - Park, Jun-Bean AU - Park JB AD - Division of Cardiology, Department of Internal Medicine/Cardiovascular Center, Seoul National University Hospital, Seoul, Korea. FAU - Koo, Bon-Kwon AU - Koo BK FAU - Choi, Woong-Gil AU - Choi WG FAU - Kim, Seok-Yeon AU - Kim SY FAU - Park, Jinsik AU - Park J FAU - Kwan, Jun AU - Kwan J FAU - Park, Chang Gyu AU - Park CG FAU - Kim, Hyo-Soo AU - Kim HS LA - eng SI - ClinicalTrials.gov/NCT01584791 PT - Clinical Trial, Phase IV PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (P2RY12 protein, human) RN - 0 (Platelet Aggregation Inhibitors) RN - 0 (Purinergic P2Y Receptor Antagonists) RN - 0 (Receptors, Purinergic P2Y12) RN - A74586SNO7 (Clopidogrel) RN - OM90ZUW7M1 (Ticlopidine) SB - IM MH - Aged MH - Blood Platelets/*drug effects/metabolism MH - Cerebrovascular Disorders/blood/etiology/prevention & control MH - Chi-Square Distribution MH - Clopidogrel MH - Coronary Artery Disease/mortality/*therapy MH - Female MH - Humans MH - Male MH - Middle Aged MH - Myocardial Infarction/blood/etiology/prevention & control MH - *Percutaneous Coronary Intervention/adverse effects/mortality MH - Platelet Aggregation/drug effects MH - Platelet Aggregation Inhibitors/adverse effects/*therapeutic use MH - Platelet Function Tests MH - Point-of-Care Systems MH - Prospective Studies MH - Purinergic P2Y Receptor Antagonists/adverse effects/*therapeutic use MH - Receptors, Purinergic P2Y12/drug effects/metabolism MH - Republic of Korea MH - Therapeutic Equivalency MH - Ticlopidine/adverse effects/*analogs & derivatives/therapeutic use MH - Time Factors MH - Treatment Outcome EDAT- 2013/01/19 06:00 MHDA- 2013/07/03 06:00 CRDT- 2013/01/19 06:00 PHST- 2012/09/08 00:00 [received] PHST- 2012/12/09 00:00 [revised] PHST- 2012/12/12 00:00 [accepted] PHST- 2013/01/19 06:00 [entrez] PHST- 2013/01/19 06:00 [pubmed] PHST- 2013/07/03 06:00 [medline] AID - S0149-2918(12)00670-4 [pii] AID - 10.1016/j.clinthera.2012.12.004 [doi] PST - ppublish SO - Clin Ther. 2013 Jan;35(1):28-37.e4. doi: 10.1016/j.clinthera.2012.12.004.