Unstable angina: tirofiban was more effective than heparin at preventing cardiac events.

Clinical bottom line (level 1b)

  1. Tirofiban was more effective than heparin at reducing cardiac events in patients with unstable angina (NNT = 56 at 48 hours) , mainly by reducing refractory angina (NNT = 56 at 48 hours) .
  2. However, tirofiban was no better than heparin at preventing cardiac events at seven days or one month.
  3. More patients on tirofiban developed thrombocytopenia (NNT = 140 at 30 days) . The effect on major bleeds was unclear.
The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study investigators : New England Journal of Medicine 1998; 338 (21): 1498-1505
Expires June 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 128 acute hospitals, 25 countries worldwide

3232 patients (aged mean 62 years, 68% male) unstable angina
  • ECG- myocardial ischaemia in two contiguous leads during an episode of chest pain with new, persistent or transient ST segment depression 0.1 mV or more, or T wave inversion, or transient ST elevation (lasting <20 minutes)
  • elevated cardiac enzymes consistent with occurrence of non-Q wave MI
  • history of MI, PTCA within 6 months, CABG within one month, positive exercise or nuclear stress test, or narrowing of 50% or more of a major coronary artery on angiogram


Excluded if
  • most recent epsiode of chest pain at rest, or accelerating angina >24 hours before randomisation
  • received thrombolysis within previous 48 hours
  • allergy or intolerance of heparin
  • creatinine >221 mmol/dl
  • active bleeding disorder
  • history of GI bleeding, hematuria, positive faecal occult blood test
  • known coagulopathy, platelet disorder or history of thrombocytopenia
  • persistent blood pressure >180/110 mm Hg
  • history of stroke or transient ischaemic attack
  • major surgery within one month
  • active peptic ulceration within three months
  • invasive procedure within 14 days that would substantially increase the risk of haemorrhage


    • Control Group: (n = 1616, 1616 analysed): heparin 5000 unit bolus, then 1000 units/hr for 48 hours ( the dose was adjusted so aPTT 2.0)
    Experimental Group: (n = 1616, 1616 analysed): tirofiban , loading dose 0.6 µ g/kg/min for 30 minutes, then 0.15 µ g/kg/min for 47.5 hours
    All patients received 300-325 mg aspirin po once daily.
    100% followed for 30 days
    Outcome notes:
    • refractory ischaemic : recurrent anginal chest pain with ischaemic ST-T changes lasting >20 minutes or trwo lasting 10 minutes within one hour despite full medical therapy
    • thrombocytopenia : platelet <90

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    any cardiac event 48 hours 90
    (5.57%)    		 61
    (3.77%)    		 32%
    (7% to 51%)    		 1.79%
    (0.34% to 3.25%)    		 56
    (31 to 290)
    refractory ischaemic 48 hours 86
    (5.32%)    		 57
    (3.53%)    		 34%
    (8% to 52%)    		 1.79%
    (0.38% to 3.21%)    		 56
    (31 to 270)
    any cardiac event 7 days 181
    (11.2%)    		 166
    (10.3%)    		 8%
    (-12% to 25%)    		 0.93%
    (-1.21% to 3.06%)    		 110
    (NNT = 33 to infinity;
    NNH = 83 to infinity)
    any cardiac event 30 days 276
    (17.1%)    		 257
    (15.9%)    		 7%
    (-9% to 20%)    		 1.18%
    (-1.38% to 3.73%)    		 85
    (NNT = 27 to infinity;
    NNH = 72 to infinity)
    thrombocytopenia 30 days 6
    (0.37%)    		 18
    (1.11%)    		 -200%
    (-654% to -19%)    		 -0.74%
    (-1.33% to -0.15%)    		 -140
    (-660 to -75)
    major bleed 30 days 18
    (1.11%)    		 18
    (1.11%)    		 0%
    (-91% to 48%)    		 0.00%
    (-0.72% to 0.72%)    		 inf
    (NNT = 138 to infinity;
    NNH = 138 to infinity)

    Comments

    1. Tirofiban is platelet glycoprotein IIb/IIIa receptor antagonist and blocks the final step in platelet aggregation, preventing cross-linking of platelets by fibrinogen.
    2. LMWH has been shown to be more effective than heparin in unstable angina for reducing cardiac events. Tirofiban needs to be compared against LMWH before widespread use.

    Citation

    1. The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study investigators , : A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. New England Journal of Medicine 1998; 338 (21): 1498-1505
    Search Terms: hand search
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: Richard Koopmans

    Clinical Question.
    Patient unstable angina
    Intervention or Exposure tirofiban
    Comparison heparin
    Outcome death, MI, ischaemia