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.