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Platelet-Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms - PRISM-PLUS
Description:
Tirofiban for death/MI/recurrent ischemia in acute coronary syndromes.
Hypothesis:
To evaluate tirofiban in the treatment of unstable angina and non-Q-wave myocardial infarction.
Study Design
Study Design:
Patients Screened: Not given
Patients Enrolled: 1,915
Mean Follow Up: 6 months
Mean Patient Age: 63
Female: 33
Patient Populations:
Prolonged anginal pain or repetitive episodes of angina at rest or during minimal exercise in the previous 12 hours.
New transient or persistent ST-T ischemic changes on the electrocardiogram (ST-segment elevation or depression of 0.1 mV or more, T-wave inversion of 0.3 mV or more in three or more limb leads or four or more precordial leads excluding V(1)), or pseudonormalization of 0.1 mV or more) or an elevation of plasma levels of creatine kinase and of the creatine kinase MB fraction (CK-MB).
Exclusions:
ST-segment elevation lasting more than 20 minutes
Thrombolysis in the previous 48 hours
Coronary angioplasty within the previous 6 months
Bypass surgery within the previous month
Angina caused by identifiable factors
History of a platelet disorder or thrombocytopenia
Active bleeding or a high risk of bleeding
Stroke within the previous year.
Serum creatinine values above 2.5mg per deciliter (220 micromol per liter)
Platelet count below 150,000 per cubic millimeter
Primary Endpoints:
Death, myocardial infarction, or refractory ischemia within seven days after randomization.
Secondary Endpoints:
Death, myocardial infarction, or refractory ischemia at 48 hours and 30 days after randomization
The three components of this end point as separate measures.
Composite of death and myocardial infarction.
Drug/Procedures Used:
Tirofiban (0.6 mcg/kg/min for 30 min, followed by infusion of 0.15 mcg/kg/min ); tirofiban (0.4 mcg/kg/min for 30 min, followed by infusion of 0.1 mcg/kg/min) plus adjusted-dose heparin; or adjusted-dose heparin
Concomitant Medications:
Aspirin
Principal Findings:
Mortality at seven days was 4.6 percent in the tirofiban-only group (16 of 345 patients died), 1.1 percent in the heparin-only group (4 of 350 patients died), and 1.5 percent in the combination-therapy group (5 of 336 patients died). The risk ratio for death at seven days with tirofiban alone, as compared with heparin alone, was 4.11 (95 percent confidence interval, 1.37 to 12.29; P=0.012), and the risk ratio for death or myocardial infarction was 1.35 (95 percent confidence interval, 0.82 to 2.29).
The frequency of the composite primary end point at 7 days was lower among the patients who received tirofiban plus heparin than among those who received heparin alone (12.9 percent vs. 17.9 percent; risk ratio, 0.68; 95 percent confidence interval, 0.53 to 0.88; P=0.004).
At 30 days rates of the composite end point in the tirofiban-plus-heparin group were also lower than those in the heparin-only group (18.5 percent vs. 22.3 percent, P=0.03).
At 6 months there remained a significant reduction of composite events by tirofiban with heparin compared to heparin alone (27.7 percent vs. 32.1 percent, P=0.02).
Major bleeding occurred in 3.0 percent of the patients receiving heparin alone and 4.0 percent of the patients receiving combination therapy (P=0.34).
Interpretation:
The entry criteria in PRISM-PLUS required more severe clinical expression of unstable angina than was required in the PRISM trial. Although the doses of tirofiban without heparin were the same in the two trials, the drug was administered for a longer period in the PRISM-PLUS trial and was continued in patients who underwent angiography or coronary procedures. The findings in the discontinued group in PRISM-PLUS were not consistent with those of PRISM, which included almost five times as many patients as were in the tirofiban-only group in PRISM-PLUS. The most likely explanation for these results is chance, but an effect of heparin rebound cannot be excluded.
The results of PRISM and PRISM-PLUS suggest that tirofiban with heparin is an effective regimen for non-ST elevation acute coronary syndromes.
References:
1. N Engl J Med 1998;338:1488-97. Final results
Keywords: Odds Ratio, Acute Coronary Syndrome, Myocardial Infarction, Creatine Kinase, Platelet Aggregation Inhibitors, Heparin, Fibrinolytic Agents, Electrocardiography, Tyrosine, Confidence Intervals, Platelet Glycoprotein GPIIb-IIIa Complex
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