title: Salts of Clopidogrel: Investigation to Ensure Clinical Equivalence: A 12-Month Randomized Clinical Trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
authors.affiliation: Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Ioannis V
authors.initials: IV
authors.lastname: Ntalas
authors.affiliation: Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Kallirroi I
authors.initials: KI
authors.lastname: Kalantzi
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Tsoumani
authors.affiliation: General Hospital of Trikala, Trikala, Greece.
authors.forename: Adamantios
authors.initials: A
authors.lastname: Bourdakis
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Charmpas
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Zaharias
authors.initials: Z
authors.lastname: Christogiannis
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Dimoulis
authors.affiliation: Department of Cardiology, General Hospital of Corfu, Corfu island, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Draganigos
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Efthimiadis
authors.affiliation: First Cardiology Department, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Giorgos
authors.initials: G
authors.lastname: Giannakoulas
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Giatrakos
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Giogiakas
authors.affiliation: Department of Cardiology, Euroclinic, Athens, Greece.
authors.forename: Giorgos
authors.initials: G
authors.lastname: Goumas
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Giorgos
authors.initials: G
authors.lastname: Hatziathanasiou
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Kazakos
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kipouridis
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Spiros
authors.initials: S
authors.lastname: Konstantinou
authors.affiliation: Department of Internal Medicine, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Haralampos
authors.initials: H
authors.lastname: Milionis
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Nikolopoulos
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Peltekis
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Prokopakis
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sinteles
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Stroumbis
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Kyriafina
authors.initials: K
authors.lastname: Terzoudi
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Thoma
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Karmelos
authors.initials: K
authors.lastname: Tsilias
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vakalis
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Vardakis
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Vasilakopoulos
authors.affiliation: Department of Clinical Therapeutics, Medical School of Athens, Alexandra Hospital, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Vemmos
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Voukelatou
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Xaraktsis
authors.affiliation: School of Health Science & Education, Harokopio University, Athens, Greece.
authors.forename: Demosthenes B
authors.initials: DB
authors.lastname: Panagiotakos
authors.affiliation: Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: John A
authors.initials: JA
authors.lastname: Goudevenos
authors.affiliation: Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece atselep@uoi.gr.
authors.forename: Alexandros D
authors.initials: AD
authors.lastname: Tselepis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000077144:Clopidogrel; D004339:Drug Compounding; D016568:Drugs, Generic / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D006115:Greece; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D011446:Prospective Studies; D012307:Risk Factors; D055502:Secondary Prevention / Q000379:methods*; D020521:Stroke / Q000209:etiology; D013810:Therapeutic Equivalency; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016568:Drugs, Generic; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: carotid artery disease; clopidogrel besylate; coronary artery disease; generic clopidogrel; peripheral artery disease; stroke