Unstable angina: refractory: a glycoprotein IIb/IIIa inhibitor reduced death, MI and urgent revascularisation.

Clinical bottom line (level 1b)

  1. In patients with unstable angina refractory to heparin and nitrates, adding a glycoprotein IIb/IIIa inhibitor reduced death, MI and urgent revascularisation in the next 24 hours (NNT = 5 at 24 hours) .
Simoons et al: Circulation 1994; 89: 596-603
Expires July 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: university hospital, Holland

60 patients (aged range 21 to 75 years, ?% male) chest pain and concomitant dynamic ST-T changes, continuing despite bed rest and medical treatment (heparin and nitrates)

Excluded if
  • more than one potential culprit lesion on angiography
  • ischaemia requiring immediate surgery
  • prior PTCA <6 months
  • prior MI
  • prior non-Q-wave infarct less than 7 days ago
  • female with child-bearing potential
  • major trauma (surgery, resuscitation, bleeding) <6 weeks
  • bleeding diathesis or platelets <100000/mm ³
  • hepatic or renal failure
  • known autoimmune disorders


    • Control Group: (n = 30, 30 analysed): placebo
    Experimental Group: (n = 30, 30 analysed): c7E3 Fab iv bolus 0.25 mg/kg, followed by infusion of 10 µ g/min
    All patients received heparin (adjusted so aPTT 1.5 to 2.5), aspirin 80 mg po or more once daily and iv nitroglycerin (at 50 to 200 µ g/min). Beta-blockers and calcium channel antagonists were used discretionary. Study medication started within one hour of angioplasty and continued until angioplasty until angioplasty completed (24 hours later).
    100% followed for 24 hours

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death, MI, urgent revascularisation 24 hours 7
    (23.3%)    		 1
    (3.33%)    		 86%
    (-9% to 98%)    		 20.0%
    (2.56% to 36.4%)    		 5
    (3 to 28)
    blood transfusion required 24 hours 2
    (6.67%)    		 3
    (10.0%)    		 -50%
    (-734% to 73%)    		 -3.33%
    (-17.3% to 10.6%)    		 -30
    (NNT = 9 to infinity;
    NNH = 6 to infinity)

    Comments

    1. c7Eb is a potent inhibitor of platelet activation and aggregation.
    2. More patients on placebo had multivessel disease (6 vs 15, p<0.05) giving this group a worse prognosis. This combined with the short follow-up makes these results less certain.
    3. How does adding C7Eb compare with adding more standard medical therapy instead (e.g.. beta-blocker)? Difficult to know how to apply this study more generally.

    Citation

    1. Simoons ML, de Boer MJ, van den Brand Mj, et al: Randomised trial of GPIIb/IIIa platelet receptor blocker in refractory unstable angina. Circulation 1994; 89: 596-603
    Contributor: Nick Shenker and Chris Ball, July 2000
    Reviewer:

    Clinical Question.
    Patient unstable angina
    Intervention or Exposure glycoprotein IIb/IIIa inhibitor
    Outcome death, MI, revascularisation