RESUMO
BACKGROUND: In the present clinical trial, we compared the efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulfate (CHS) salt in patients eligible to receive clopidogrel. METHODS: A prospective 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n = 1864) were screened and 1800 were enrolled in the trial and randomized to CHS or CB. Primary efficacy end point was the composite of myocardial infarction, stroke, or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium criteria. RESULTS: At 12-month follow-up, no differences were observed between CB (n = 759) and CHS (n = 798) in primary efficacy and safety end points (age, sex, history of percutaneous coronary intervention adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.21 and OR, 0.81; 95% CI, 0.51-1.29, respectively) between CHS and CB. Analyses of efficacy and safety in subgroups that were defined according to the qualifying diagnosis revealed that there was no difference between CHS and CB. CONCLUSION: The efficacy and safety of CB administered for 12 months for the secondary prevention of atherothrombotic events are similar to that of CHS. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE trial; ClinicalTrials.gov Identifier:NCT02126982).
Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Medicamentos Genéricos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Prevenção Secundária/métodos , Ticlopidina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Clopidogrel , Composição de Medicamentos , Medicamentos Genéricos/efeitos adversos , Medicamentos Genéricos/química , Feminino , Grécia , Hemorragia/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Razão de Chances , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/química , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Equivalência Terapêutica , Ticlopidina/efeitos adversos , Ticlopidina/química , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The aim of the present interim analysis was to compare the clinical efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulphate (CHS) salt in patient groups eligible to receive clopidogrel. METHODS: A 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n=1,864) were screened and 1,800 were enrolled in the trial and randomized to CHS (n=759) or CB (n=798). Primary efficacy end point was the composite of myocardial infarction, stroke or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 6-months follow-up no differences were observed between CB and CHS in primary efficacy end point (OR, 0.80; 95% CI, 0.37 to 1.71; p=0.57). Rates of BARC-1,-2,-3a and -5b bleeding were similar between the two study groups whereas no bleeding events according to BARC-3b, -3c, -4 and -5a were observed in either CHS or CB group. CONCLUSION: The clinical efficacy and safety of the generic CB is similar to that of the innovator CHS salt, thus, it can be routinely used in the secondary prevention of atherothrombotic events for a period of at least 6 months. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE study Clinical Trials.gov Identifier: NCT02126982).
