Benefits and safety of tirofiban among acute coronary syndrome patients with mild to moderate renal insufficiency: results from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial.

BACKGROUND: The role of glycoprotein IIb/IIIa receptor antagonists for the treatment of patients with acute coronary syndrome and renal insufficiency remains undefined. METHODS AND RESULTS: Patients from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial were stratified by creatinine clearance (CrCl) and assessed with respect to treatment assignment to tirofiban/heparin versus heparin alone for the risk of adverse outcomes and bleeding. Patients with severe renal insufficiency (defined as a serum creatinine > or = 2.5 mg/dL) were excluded from PRISM-PLUS as a whole. Patients with the lowest CrCl (< 30 mL/min) were more likely to present with high-risk clinical features. Decreasing renal function was strongly associated with adverse outcome, increasing the risk for ischemic complications at all time points examined (all P < 0.002). Irrespective of CrCl, therapy with tirofiban reduced the odds of the composite end point of death, myocardial infarction, or refractory ischemia at 48 hours (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.46 to 1.0; P=0.05), 7 days (OR, 0.68; 95% CI, 0.52 to 0.88; P= 0.003), 30 days (OR, 0.78; 95% CI, 0.63 to 0.98; P=0.03), and 6 months (OR, 0.81; 95% CI, 0.68 to 0.98; P=0.03). The risk of myocardial infarction/death was also significantly decreased to a similar magnitude at all time points examined. There was no evidence of treatment-by-CrCl interaction. The presence of declining renal function independently increased the risk for bleeding (OR, 1.57; P < 0.001 for trend across categories), as did therapy with tirofiban, but no unexpected incremental risk of bleeding due to tirofiban was observed among lowest CrCl categories. CONCLUSIONS: Among patients with mild-to-moderate renal insufficiency in PRISM-PLUS, tirofiban was well tolerated and effective in reducing ischemic acute coronary syndrome complications.