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

Jun Bean Park, Bon Kwon Koo, Woong Gil Choi, Seok Yeon Kim, Jinsik Park, Jun Kwan, Chang Gyu Park, Hyo Soo Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

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. 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 P2Y12 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 P2Y12 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. ClinicalTrials.gov identifier: NCT01584791.

Original languageEnglish
JournalClinical Therapeutics
Volume35
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

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clopidogrel
Percutaneous Coronary Intervention
Coronary Artery Disease
Control Groups
Korea
Drug-Related Side Effects and Adverse Reactions
Aspirin
Phase IV Clinical Trials

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

@article{62cc9315cb654cd79461170096ecfdcd,
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. 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 P2Y12 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 P2Y12 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. ClinicalTrials.gov identifier: NCT01584791.",
author = "Park, {Jun Bean} and Koo, {Bon Kwon} and Choi, {Woong Gil} and Kim, {Seok Yeon} and Jinsik Park and Jun Kwan and Park, {Chang Gyu} and Kim, {Hyo Soo}",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.clinthera.2012.12.004",
language = "English",
volume = "35",
journal = "Clinical Therapeutics",
issn = "0149-2918",
publisher = "Excerpta Medica",
number = "1",

}

TY - JOUR

T1 - Comparison of Antiplatelet Efficacy and Tolerability of Clopidogrel Napadisilate With Clopidogrel Bisulfate in Coronary Artery Disease Patients After Percutaneous Coronary Intervention

T2 - A Prospective, Multicenter, Randomized, Open-Label, Phase IV, Noninferiority Trial

AU - Park, Jun Bean

AU - Koo, Bon Kwon

AU - Choi, Woong Gil

AU - Kim, Seok Yeon

AU - Park, Jinsik

AU - Kwan, Jun

AU - Park, Chang Gyu

AU - Kim, Hyo Soo

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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. 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 P2Y12 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 P2Y12 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. ClinicalTrials.gov identifier: NCT01584791.

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. 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 P2Y12 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 P2Y12 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. ClinicalTrials.gov identifier: NCT01584791.

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