PMID- 27539685 OWN - NLM STAT- MEDLINE DCOM- 20170925 LR - 20181202 IS - 1876-7605 (Electronic) IS - 1936-8798 (Linking) VI - 9 IP - 16 DP - 2016 Aug 22 TI - 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. PG - 1667-76 LID - S1936-8798(16)30651-3 [pii] LID - 10.1016/j.jcin.2016.05.031 [doi] AB - OBJECTIVES: 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). BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CI - Copyright (c) 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Adamo, Marianna AU - Adamo M AD - Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Catheterization Laboratory, Spedali Civili, Brescia, Italy. FAU - Ariotti, Sara AU - Ariotti S AD - Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Cardiology, Bern University Hospital, Bern, Switzerland. FAU - Costa, Francesco AU - Costa F AD - Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Clinical and Experimental Medicine, Policlinico "G. Martino," Messina, Italy. FAU - Curello, Salvatore AU - Curello S AD - Catheterization Laboratory, Spedali Civili, Brescia, Italy. FAU - Moschovitis, Aris AU - Moschovitis A AD - Department of Cardiology, Bern University Hospital, Bern, Switzerland. FAU - de Vries, Ton AU - de Vries T AD - Cardialysis BV, Rotterdam, the Netherlands. FAU - White, Harvey D AU - White HD AD - Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand. FAU - Windecker, Stephan AU - Windecker S AD - Department of Cardiology, Bern University Hospital, Bern, Switzerland. FAU - Valgimigli, Marco AU - Valgimigli M AD - Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Cardiology, Bern University Hospital, Bern, Switzerland. Electronic address: marco.valgimigli@insel.ch. LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - JACC Cardiovasc Interv JT - JACC. Cardiovascular interventions JID - 101467004 RN - 0 (Buffers) RN - 0 (Citrates) RN - 0 (Drugs, Generic) RN - 0 (Phosphates) RN - 0 (Platelet Aggregation Inhibitors) RN - 42HK56048U (Tyrosine) RN - 9005-49-6 (Heparin) RN - GGX234SI5H (Tirofiban) SB - IM CIN - JACC Cardiovasc Interv. 2016 Aug 22;9(16):1677-9. PMID: 27539686 MH - Acute Coronary Syndrome/blood/diagnosis/*therapy MH - Aged MH - Buffers MH - Chi-Square Distribution MH - Citrates/*adverse effects/chemistry MH - Double-Blind Method MH - Drug Compounding MH - Drug Stability MH - Drugs, Generic/*adverse effects/chemistry MH - Female MH - Heparin/*adverse effects/chemistry MH - Humans MH - Kaplan-Meier Estimate MH - Logistic Models MH - Male MH - Middle Aged MH - Odds Ratio MH - Phosphates/*adverse effects/chemistry MH - Platelet Aggregation Inhibitors/*adverse effects/chemistry MH - Proportional Hazards Models MH - Risk Factors MH - Thrombocytopenia/blood/*chemically induced/diagnosis MH - Time Factors MH - Tirofiban MH - Treatment Outcome MH - Tyrosine/adverse effects/*analogs & derivatives/chemistry OTO - NOTNLM OT - buffers OT - non-ST-segment elevation acute coronary syndrome OT - thrombocytopenia OT - tirofiban EDAT- 2016/08/20 06:00 MHDA- 2017/09/26 06:00 CRDT- 2016/08/20 06:00 PHST- 2016/01/28 00:00 [received] PHST- 2016/05/09 00:00 [revised] PHST- 2016/05/18 00:00 [accepted] PHST- 2016/08/20 06:00 [entrez] PHST- 2016/08/20 06:00 [pubmed] PHST- 2017/09/26 06:00 [medline] AID - S1936-8798(16)30651-3 [pii] AID - 10.1016/j.jcin.2016.05.031 [doi] PST - ppublish SO - JACC Cardiovasc Interv. 2016 Aug 22;9(16):1667-76. doi: 10.1016/j.jcin.2016.05.031.