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/mm3 or <100,000/mm3) 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 ¼ 0.027; and OR: 2.83; 95% CI: 1.11 to 7.22; p ¼ 0.029, respectively) but not in patients treated with citratebuffered tirofiban in the late phase (OR: 1.01; 95% CI: 0.20 to 5.05; p ¼ 0.987; and OR: 0.99; 95% CI: 0.26 to 3.45; p ¼ 0.991, respectively). Using a combined definition of thrombocytopenia (nadir <150,000/mm3 or a decrease $50%), the randomization period significantly modified the effect of the treatment (tirofiban vs. UFH) on platelet decrease (p for interaction ¼ 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. (J Am Coll Cardiol Intv 2016;9:1667–76) © 2016 by the American College of Cardiology Foundation.