title: Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized Observational Study.
abstract: OBJECTIVE
  The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention.
  
  
  BACKGROUND
  Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients.
  
  
  METHODS
  Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days.
  
  
  RESULTS
  Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36).
  
  
  CONCLUSIONS
  This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Räber
authors.affiliation: University Heart Center, Cardiology, University Hospital, Zurich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Klingenberg
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Dik
authors.initials: D
authors.lastname: Heg
authors.affiliation: Cardiac Catheterization Laboratory, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Kelbæk
authors.affiliation: Division of Cardiology, University Hospital, Geneva, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Roffi
authors.affiliation: Cardiology Department, Triemlispital, Zurich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Tüller
authors.affiliation: Bristol Heart Institute, Bristol, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baumbach
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zanchin
authors.affiliation: Division of Cardiology, University Hospital, Geneva, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Carballo
authors.affiliation: Department of Cardiology, Belgrade University Hospital, Belgrade, Serbia.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Ostojic
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern Switzerland.
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Stefanini
authors.affiliation: Department of Internal Medicine, Bern University Hospital, Bern, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
authors.affiliation: Department of Cardiology, Thoraxcentrum Twente and University of Twente, Enschede, the Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: von Birgelen
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern Switzerland.
authors.forename: Aris
authors.initials: A
authors.lastname: Moschovitis
authors.affiliation: Cardiac Catheterization Laboratory, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Engstrøm
authors.affiliation: Division of Cardiology, University Hospital, Geneva, Switzerland.
authors.forename: Baris
authors.initials: B
authors.lastname: Gencer
authors.affiliation: Department of Medicine, University Hospital Lausanne, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Auer
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Meier
authors.affiliation: Division of Cardiology, University Hospital, Geneva, Switzerland.
authors.forename: Francois
authors.initials: F
authors.lastname: Mach
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern Switzerland.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Clinical Trials Unit, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Jüni
authors.affiliation: University Heart Center, Cardiology, University Hospital, Zurich, Switzerland.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Matter
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern Switzerland; Clinical Trials Unit, Department of Clinical Research, University of Bern, Bern, Switzerland. Electronic address: stephan.windecker@insel.ch.
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D004334:Drug Administration Schedule; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013557:Switzerland; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: P2Y(12) inhibitors; ST-segment elevation myocardial infarction; antiplatelet therapy; clopidogrel; prasugrel