Thrombocytopenia Risk in Tirofiban vs Heparin

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.