title: Phosphate- or Citrate-Buffered Tirofiban Versus Unfractionated Heparin and its Impact on Thrombocytopenia and Clinical Outcomes in Patients With Acute Coronary Syndrome: A Post Hoc Analysis From the PRISM Trial.
abstract: The aim of this study was to investigate whether the 2 tirofiban formulations tested in the early and late phases of the PRISM (Platelet Receptor Inhibitor in Ischemic Syndrome Management) trial might differ with respect to risk for thrombocytopenia and clinical outcomes compared with unfractionated heparin (UFH).
  
  
  
  Citrate-buffered tirofiban is currently marketed as brand-name drug. However, tirofiban has recently been promoted in some countries as a generic drug with different formulations, such as phosphate-buffered product.
  
  
  
  In the PRISM trial 3,232 patients were randomly assigned to receive tirofiban or UFH. In the early phase, 879 patients were allocated to phosphate-buffered tirofiban and 874 patients to UFH group. After a protocol amendment due to a study drug instability report, citrate-buffered tirofiban replaced the phosphate-buffered formulation. Therefore, in the late phase, 737 and 742 patients were treated with citrate-buffered tirofiban and UFH, respectively.
  
  
  
  The relative risk for thrombocytopenia (nadir <90,000/mm(3) or <100,000/mm(3)) was increased in patients treated with phosphate-buffered tirofiban in the early phase (odds ratio [OR]: 3.51; 95% confidence interval [CI]: 1.15 to 10.73; p = 0.027; and OR: 2.83; 95% CI: 1.11 to 7.22; p = 0.029, respectively) but not in patients treated with citrate-buffered tirofiban in the late phase (OR: 1.01; 95% CI: 0.20 to 5.05; p = 0.987; and OR: 0.99; 95% CI: 0.26 to 3.45; p = 0.991, respectively). Using a combined definition of thrombocytopenia (nadir <150,000/mm(3) or a decrease ≥50%), the randomization period significantly modified the effect of the treatment (tirofiban vs. UFH) on platelet decrease (p for interaction = 0.024). Thrombocytopenia was associated with a 5- to 10-fold increased risk for TIMI (Thrombolysis In Myocardial Infarction) bleeding and a 2-fold increased risk for net adverse cardiovascular events.
  
  
  
  Phosphate-buffered tirofiban, currently marketed as a generic drug, is associated with a higher rate of thrombocytopenia with a potentially increased risk for adverse clinical outcomes compared with citrate-buffered tirofiban.
authors.affiliation: Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Catheterization Laboratory, Spedali Civili, Brescia, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Adamo
authors.affiliation: Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Ariotti
authors.affiliation: Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Clinical and Experimental Medicine, Policlinico "G. Martino," Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Costa
authors.affiliation: Catheterization Laboratory, Spedali Civili, Brescia, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Curello
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Aris
authors.initials: A
authors.lastname: Moschovitis
authors.affiliation: Cardialysis BV, Rotterdam, the Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: de Vries
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.affiliation: Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Cardiology, Bern University Hospital, Bern, Switzerland. Electronic address: marco.valgimigli@insel.ch.
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D000368:Aged; D002021:Buffers; D016009:Chi-Square Distribution; D002951:Citrates / Q000009:adverse effects* / Q000737:chemistry; D004311:Double-Blind Method; D004339:Drug Compounding; D004355:Drug Stability; D016568:Drugs, Generic / Q000009:adverse effects* / Q000737:chemistry; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010710:Phosphates / Q000009:adverse effects* / Q000737:chemistry; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000737:chemistry; D016016:Proportional Hazards Models; D012307:Risk Factors; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D013997:Time Factors; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D002021:Buffers; D002951:Citrates; D016568:Drugs, Generic; D010710:Phosphates; D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; D006493:Heparin; D000077466:Tirofiban
keywords: buffers; non–ST-segment elevation acute coronary syndrome; thrombocytopenia; tirofiban