Patients assigned to generic phosphate-buffered tirofiban were more likely to experience thrombocytopenia compared to patients assigned to citrate-buffered tirofiban or unfractionated heparin, according to post hoc results from the PRISM clinical trial.
Findings were recently published in JACC: Cardiovascular Interventions.
PRISM (Platelet Receptor Inhibitor in Ischemic Syndrome Management) was a randomized, controlled, multicenter, double-blind involving patients with non–ST-segment elevation acute coronary syndrome.
In the early recruitment phase, Marianna Adamo, MD, of the Thoraxcenter in Rotterdam, the Netherlands and colleagues randomly assigned patients to either 0.6 mg/kg/min phosphate-buffered tirofiban followed by 0.15 mg/kg/min infusion for 48 hours (n=879) or 5000 IU unfractionated heparin followed by an infusion of 1000 IU/h for 48 hours. During the late recruitment phase, patients were assigned to citrate-buffered tirofiban (n=737) or unfractionated heparin (n=742).
Thrombocytopenia was defined as platelet nadir <90 000/mm3 platelet count <100 000/mm3, and as a combination of nadir value <150 000/mm3 and decrease of platelet count ≥50%.
Researchers found that the rate of thrombocytopenia was significantly higher for patients assigned to phosphate-buffered tirofiban, but not those assigned to unfractionated heparin or citrate-buffered tirofiban (see tables).
Rate of thrombocytopenia (early recruitment phase)
Medication |
90 000/mm3 |
100 000/ mm3 |
Phosphate-buffered tirofiban |
1.7% |
2.0% |
Unfractionated heparin |
0.5% |
0.7% |
Rate of thrombocytopenia (late recruitment phase)
Medication |
90 000/mm3 |
100 000/ mm3 |
Citrate-buffered tirofiban |
0.3% |
0.7% |
Unfractionated heparin |
0.1% |
0.7% |
Patients who developed thrombocytopenia were more likely to discontinue the study prematurely, both at a platelet nadir of <90 000/mm3 (45.8% vs 1.7%) and at a platelet nadir of 100 000/mm3 (42.2% vs 1.6%; P<.001 for all).
In addition, patients who experienced a platelet nadir <100,000/mm3 had a 2-fold increased risk for net adverse cardiovascular events (hazard ratio: 2.36; 95% confidence interval: 1.31-4.23; P=.004).
Thrombocytopenia was associated with a 5- to 10-fold increased risk for thrombolysis in myocardial infarction (TIMI) bleeding and a 2-fold increased risk for net adverse cardiovascular events, the authors concluded.
Reference
Adamo M, Ariotti S, Costa F, et al. Phosphate- or citrate-buffered tirofiban vs unfractionated heparin and its impact on thrombocytopenia and clinical outcomes in patients with acute coronary syndrome. JACC Cardiovasc Interv. 2016;9:1667-1676. doi:10.1016/j.jcin.2016.05.031.