Acute coronary syndrome: abciximab caused bleeding and thrombocytopenia without clearly reducing death or myocardial infarction

Clinical bottom line (level 1b)

  1. Patients with acute coronary syndrome (ST depression or a positive troponin) who received abciximab compared with placebo were more likely to die (NNH = 210 at 48 hours) , and not clearly less likely to have a myocardial infarction within 48 hours.
  2. Patients given abciximab were not clearly less likely to die or have a myocardial infarction at 7 or 30 days, nor less likely to undergo revascularisation within 30 days.
  3. Patients given abciximab were more likely to have major bleeding (NNH = 190 at 30 days) or develop thrombocytopenia (NNH = 68 at 30 days) .
The GUSTO IV-ACS Investigators : Lancet 2001; 357 : 1915-1924
Expires April 2004

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 458 hospitals in 24 countries worldwide

7800 patients (aged mean 65, 63% male) acute coronary syndrome (1 or more episodes of angina lasting at least 5 minutes within previous 24 hours) with transient or persistent ST depression or a positive troponin T or I

Excluded if
  • weight > 120 kg
  • co-existing disorder expected to limit life expectancy
  • allergy to abciximab or other murine proteins
  • platelet count < 100 x 10 9 /l
  • confirmed hypertenion (bp > 180/110)
  • history of vasculitis
  • puncture of non-compressible vessel within 24 hours of enrolment
  • history of stroke within 2 years, or leaving residual neurological deficit
  • oral anticoagulation within previous 7 days, unless INR 1.4 or less
  • active internal bleeding or history of haemorrhagic diathesis
  • major surgery, trauma or GI/GU bleeding of clinical significance in previous 6 weeks
  • intracranial neoplasm, aneursym, AV malformation
  • aged < 21
  • ST elevation < 0.5 mm, or attributable to coexisting disease (LV hypertrophy) or medication (digoxin)
  • myocardial ischaemia precipated by cause other than atherosclerotic coronary artery disease
  • persistent ST elevation or new LBBB
  • percutaneous coronary intervention within previous 14 days; or planned revascularisation within next 30 days

Control Group: (n = 2598, 2598 analysed): placebo infusion
Experimental Group: (n = 2590, 2590 analysed): abciximab 0.25 mg/kg bolus followed by 0.125 microg/kg/min up to a maximum of 10 microg/min for 24 hours, followed by 24 hours of placebo infusion
Experimental Group: (n = 2612, 2612 analysed): abciximab 0.25 mg/kg bolus followed by 0.125 microg/kg/min up to a maximum of 10 microg/min for 48 hours
Patients could receive heparin or dalteparin. Beta-blocker therapy was encouraged. Other cardiac medication was left to the clinician's discretion. Patients could receive glycoprotein IIb/IIIa platelet inhibitors if undergoing PTCA.
100% followed for 30 days
Outcome notes:
  • major bleeding : intracranial haemorrhage or bleeding with a fall in Hb > 5.0 g/dl
  • thrombocytopenia : platelet count < 50 x 10 9/l

The evidence

Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
death 48 hours 8
(0.31%)		 41
(0.79%)		 -160%
(-450% to -20%)		 -0.48%
(-0.80% to -0.159%)		 -210
(-630 to -130)
myocardial infarction 48 hours 34
(1.31%)		 71
(1.36%)		 -4%
(-57% to 31%)		 -0.06%
(-0.60% to 0.48%)		 -1800
(NNT = 170 to infinity;
NNH = 210 to infinity)
death or myocardial infarction 7 days 116
(4.46%)		 209
(4.02%)		 10%
(-12% to 28%)		 0.45%
(-0.51% to 1.40%)		 220
(NNT = 200 to infinity;
NNH = 71 to infinity)
death or myocardial infarction 30 days 209
(8.04%)		 450
(8.65%)		 -8%
(-26% to 8%)		 -0.61%
(-1.90% to 0.69%)		 -170
(NNT = 53 to infinity;
NNH = 150 to infinity)
revascularisation 30 days 797
(30.7%)		 1543
(29.7%)		 3%
(-4% to 10%)		 1.02%
(-1.15% to 3.18%)		 98
(NNT = 87 to infinity;
NNH = 31 to infinity)
major bleeding 30 days 7
(0.27%)		 42
(0.81%)		 -200%
(-570% to -35%)		 -0.54%
(-0.85% to -0.22%)		 -190
(-450 to -120)
thrombocytopenia 30 days 1
(0.0385%)		 78
(1.50%)		 -3800%
(-28000% to -440%)		 -1.46%
(-1.80% to -1.12%)		 -68
(-89 to -56)

  • Abciximab given for 48 hours was not clearly better than abciximab given at 24 hours for any outcome. Therefore the two groups were combined in this analysis.

Citation

  1. The GUSTO IV-ACS Investigators , : effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet 2001; 357 : 1915-1924
Search Terms: from ACP Journal Club
Contributor: Chris Ball, April 2002
Reviewer:

Clinical Question.
Patient acute coronary syndrome
Intervention or Exposure abciximab
Comparison placebo
Outcome death, myocardial infarction, bleeding, thrombocytopenia