Unstable angina: tirofiban has no clear effect on long-term mortality.

Clinical bottom line (level 1b)

  1. Patients with unstable angina or non-Q-wave MI who were given tirofiban plus heparin were less likely to have died, had a new MI or had refractory ischaemia at 7 days, than those given heparin alone (NNT = 20 at 7 days), but this association was less strong at 6 months.
  2. Patients given tirofiban plus heparin had no clear difference in major bleeding.
The Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS)Study Investigators : New England Journal of Medicine 1998; 338 (21): 1488-1497
Expires March 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 72 hospitals in 14 countries

1570 patients (aged mean 63 years, 68% male) unstable angina or non-Q-wave myocardial infarction

Excluded if
  • ST segment elevation lasting >20 minutes
  • thrombolysis in the previous 48 hours
  • coronary angioplasty within the previous six months or bypass surgery within one month
  • angina caused by identifiable factors
  • history of platelet disorder or thrombocytopaenia
  • active bleeding or at high risk of bleeding
  • stroke within previous year
  • serum creatinine >2.5 mg/dL (220 µ mol/L)
  • platelet count <150,000/mm ³
Control Group: (n = 797, 797 analysed): adjusted-dose heparin plus tirofiban placebo
Experimental Group: (n = 773, 773 analysed): tirofiban (0.4 µ g/kg/minute for 30 minutes, followed by an infusion of 0.1 µ g/kg/minute) plus adjusted-dose heparin

100% followed for 6 months
Outcome notes:
  • major bleeding : decrease in blood haemoglobin level >4.0 g/dL, the transfusion of two or more units of blood, the need for corrective surgery, the occurrence of an intracranial or retroperitoneal haemorrhage or any combination of these.

The evidence

Outcome Time to outcome CEREERRRR
(95% CI)		NNT
(95% CI)
death, new myocardial infarction or refractory ischaemia 7 days 143
(17.9%)		 100
(12.9%)		 32%
(12% to 47%)		 17
(12 to 47)
death, new myocardial infarction or refractory ischaemia 6 months 256
(32.1%)		 214
(27.7%)		 19%
(2% to 37%)		 16
(10 to 104)
major bleeding unknown 24
(3.01%)		 31
(4.01%)		 -33.0%
(-125% to 21.0%)		 -100
(NNT = 121 to infinity;
NNH = 35 to infinity)

Comments

  1. The study also involved a tirofiban-only group, but this was stopped prematurely on the recommendation of the data and safety monitoring board, and so has not been included.

Citation

  1. The Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS)Study Investigators , : Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. New England Journal of Medicine 1998; 338 (21): 1488-1497
Contributor: Clare Wotton and Bob Phillips, January 2000
Reviewer:

Clinical Question.
Patient unstable angina
Intervention or Exposure tirofiban plus heparin
Comparison heparin
Outcome ischaemic events