Platelet-Receptor Inhibition for Ischemic Syndrome Management - PRISM


Tirofiban for death/MI/recurrent ischemia in acute coronary syndromes.


To evaluate whether inhibition of platelet aggregation with tirofiban would improve outcomes in unstable angina.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 3,232
Mean Follow Up: 6 months
Mean Patient Age: 62.5
Female: 32

Patient Populations:

Chest pain at rest or accelerating chest pain within 24 hours of randomization.
One of the following three sets of signs: (1) ECG evidence of myocardial ischemia in two contiguous leads; (2) elevated cardiac-enzyme levels consistent with non-Q-wave myocardial infarction; or (3) a history of myocardial infarction, percutaneous revascularization more than six months earlier, coronary surgery more than one month earlier, a positive exercise stress test or dipyridamole (or adenosine) nuclear stress test, or narrowing of at least 50 percent of the luminal diameter of a major coronary artery on a previous arteriogram.


Thrombolytic therapy within 48 hours
Allergy or intolerance to heparin
Renal insufficiency
Active bleeding disorder
History of gastrointestinal bleeding
Positive fecal occult-blood test
Known coagulopathy
Platelet disorder or history of thrombocytopenia
Systolic BP > 180 mmHg or diastolic BP > 110 mmHg
Hemorrhagic cerebrovascular disease
Major surgical procedure within one month
Active peptic ulceration within previous 3 months
Invasive procedure within 14 days

Primary Endpoints:

Composite of death, myocardial infarction, or refractory ischemia at the end of the 48-hour infusion.

Secondary Endpoints:

Death, myocardial infarction, or refractory ischemia at seven days.

Drug/Procedures Used:

Tirofiban, loading dose 0.6 mcg/kg/min x 30 min, then 0.15 mcg/kg/min for 47.5 hours, or heparin, 5000 unit bolus followed by 1000 units/hour for 48 hours.

Concomitant Medications:


Principal Findings:

A total of 3232 patients were randomly assigned to treatment (1616 in each group).

The incidence of the composite end point was 32 percent lower at 48 hours in the group that received tirofiban (3.8 percent, vs. 5.6 percent with heparin; risk ratio, 0.67; 95 percent confidence interval, 0.48 to 0.92; P=0.01).

At seven days, the composite end point was reached in 10.3% of the tirofiban group and 11.2% of the heparin group (P=0.33).

At 30 days, the composite end point of death, myocardial infarction, or refractory ischemia and readmission for unstable angina was similar in the two groups (15.9% in the tirofiban group vs. 17.1% in the heparin group, P=0.34). There was a trend toward a reduction in the rate of death or myocardial infarction with tirofiban (a rate of 5.8 percent, as compared with 7.1%in the heparin group; risk ratio, 0.80; 95% confidence interval, 0.61 to 1.05; P=0.11).

At 30 days, mortality was 2.3% in the tirofiban group, compared to 3.6% in the heparin group (P=0.02).

Major bleeding occurred in 0.4% of the patients in both groups. Thrombocytopenia occurred more frequently with tirofiban than with heparin (1.1% vs. 0.4 %, P=0.04).


This study compared the effect of tirofiban with that of heparin in patients who were already receiving aspirin therapy. A similar comparison was undertaken in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study, with the addition of a third study group in which patients received aspirin, tirofiban, and heparin. At the first interim analysis, the data and safety monitoring committee recommended stopping the PRISM-PLUS group given tirofiban alone because of an increase in deaths at day 7 (4.6 percent, as compared with 1.1 percent in the group that received only heparin). 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.

PRISM is the only study of IIb/IIIa inhibition to show a statistically significant mortality benefit at 30 days; however, the composite of death and myocardial infarction was not statistically significant. The results of PRISM and PRISM-PLUS suggest that tirofiban with heparin is an effective regimen for non-ST elevation acute coronary syndromes.


1. N Engl J Med 1998;338:1498-505. Final results

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Anticoagulation Management and ACS, Statins

Keywords: Odds Ratio, Myocardial Infarction, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Heparin, Blood Platelets, Fibrinolytic Agents, Electrocardiography, Tyrosine, Coronary Vessels, Confidence Intervals, Dipyridamole, Thrombocytopenia, Exercise Test, Platelet Glycoprotein GPIIb-IIIa Complex

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