Myocardial infarction: adding enoxaparin or abciximab to tenecteplase reduced reinfarction and refractory ischaemia compared with heparin, but abciximab led to more bleeding and thrombocytopenia

Clinical bottom line (level 1b)

  1. Patients with a myocardial infarction who received tenecteplase and enoxaparin compared with tenecteplase and unfractionated heparin were less likely to reinfarct (NNT = 64 at 30 days) or develop refractory ischaemia in hospital (NNT = 62 at 30 days) .
  2. There was no clear difference in death, intracranial haemorrhage, other forms of major bleeding or thrombocytopenia between the two grouops.
  3. Patients with a myocardial infarction who received half-dose tenecteplase with abciximab and unfractionated heparin compared with full-dose tenecteplase and unfractionated heparin were less likely to reinfarct (NNT = 49 at 30 days) or develop refractory ischaemia in hospital (NNT = 30 at 30 days) , but more likely to develop major bleeding (NNH = 46 at 30 days) or thrombocytopenia (NNH = 54 at 30 days) .
  4. There was no clear difference in death or intracranial haemorrhage between the two groups.
  5. Patients who received full-dose tenecteplase and enoxaparin compared with half-dose tenecteplase with abciximab and unfractionated heparin were more likely to develop refractory ischaemia in hospital (NNH = 70 at 30 days) , but less likely to have a major bleed (NNT = 81 at 30 days) or develop thrombocytopenia (NNT = 50 at 30 days) .
  6. There was no clear difference in death, reinfarction in hospital or intracranial haemorrhage between the two groups.
ASSENT-3 investigators : Lancet 2001; 358 : 605-613
Expires April 2004

The study

Unblinded concealed randomised trial with intention-to-treat
Setting: 575 acute hospitals in 26 countries worldwide

6095 patients (aged mean 61, 77% male) with an acute myocardial infarction (chest pain and ST elevation of at least 1 mm in 2 or more limb leads or at least 2 mm in 2 or more continguous chest leads, or left-bundle branch block)

Excluded if
  • aged < 18
  • known renal insufficiency (serum creatinine > 221 micromol/l for men, > 177 micromol/l for women)
  • cardiopulmonary resuscitation for > 10 min in previous 2 weeks
  • pregnancy, or post-partuor breast-feeding or
  • inability to follow protocol or be followed
  • participation in another study
  • onset of symptoms > 6 hours before randomisation
  • bp > 180/110 mmHg on repeated measurements
  • use of abciximab or other glycoprotein IIb/IIIa inhibitors within previous 7 days
  • major surgery, biopsy or parenchymal organ or substantial trauma within 2 months
  • any head injury or trauma after onset of current myocardial infarction
  • history of stroke or TIA, or known structural damage to CNS
  • current treatment with anticoagulants, including heparin

Control Group: (n = 2038, 2038 analysed): full-dose tenecteplase (30 mg if < 60 kg; 35 mg if 60-69 kg; 40 mg if 70-79 kg; 45 mg if 80-89 kg; or 50 mg if > 90 kg) over 5 sec and weight-adjusted unfractionated heparin (bolus of 60 U/kg to a maximum of 4000 U, followed by an infusion of 12 U/kg adjusted so aPTT 50-70 sec) for 48 hours
Experimental Group: (n = 2017, 2017 analysed): half-dose tenecteplase and abciximab (0.25 mg/kg bolus followed by an infusion of 0.125 microgm/kg per min; maximum 10 microgm/min) for 12 hours and weight-adjusted reduced-dose unfractionated heparin heparin (bolus of 40 U/kg to a maximum of 3000 U, followed by an infusion of 7 U/kg adjusted so aPTT 50-70 sec)
Experimental Group: (n = , analysed): full-dose tenecteplase d enoxaparin 30 mg iv bolus, followed by 1 mg/kg sc every 12 hours for up to 7 days or until revascularisation
All patients received 150-325 mg aspirin daily.
99.9% followed for 30 days
Outcome notes:
  • thrombocytopenia : platelet count < 100 x 109/l

The evidence

tenecteplase + enoxaparin v. tenecteplase + heparin
Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
death 30 days 122
(5.99%)		 109
(5.34%)		 11%
(-15% to 31%)		 0.64%
(-0.78% to 2.06%)		 160
(NNT = 130 to infinity;
NNH = 48 to infinity)
inhospital reinfarction 30 days 86
(4.22%)		 54
(2.65%)		 37%
(12% to 55%)		 1.57%
(0.46% to 2.69%)		 64
(37 to 220)
inhospital refractory ischaemia 30 days 132
(6.48%)		 93
(4.56%)		 30%
(9% to 46%)		 1.92%
(0.52% to 3.32%)		 52
(30 to 193)
inhospital intracranial haemorrhage 30 days 19
(0.93%)		 18
(0.88%)		 5%
(-80% to 50%)		 0.050%
(-0.53% to 0.63%)		 2000
(NNT = 190 to infinity;
NNH = 160 to infinity)
other major haemorrhage 30 days 44
(2.16%)		 62
(3.04%)		 -41%
(-110% to 4%)		 -0.88%
(-1.86% to 0.10%)		 -110
(NNT = 54 to infinity;
NNH = 1000 to infinity)
thrombocytopenia 30 days 27
(1.32%)		 24
(1.18%)		 11%
(-53% to 49%)		 0.15%
(-0.53% to 0.83%)		 670
(NNT = 190 to infinity;
NNH = 120 to infinity)

tenecteplase + abciximab + heparin v. tenecteplase + heparin
Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
death 30 days 122
(5.99%)		 133
(6.59%)		 -10%
(-40% to 13%)		 -0.61%
(-2.10% to 0.887%)		 -170
(NNT = 48 to infinity;
NNH = 110 to infinity)
inhospital reinfarction 30 days 86
(4.22%)		 44
(2.18%)		 48%
(26% to 64%)		 2.04%
(0.96% to 3.12%)		 49
(32 to 104)
inhospital refractory ischaemia 30 days 132
(6.48%)		 64
(3.17%)		 51%
(34% to 63%)		 3.30%
(1.99% to 4.62%)		 30
(22 to 50)
inhospital intracranial haemorrhage 30 days 19
(0.93%)		 19
(0.94%)		 -1%
(-90% to 46%)		 -0.00097%
(-0.60% to 0.58%)		 -10000
(NNT = 170 to infinity;
NNH = 170 to infinity)
other major bleeding 30 days 44
(2.16%)		 87
(4.31%)		 -100%
(-190% to -40%)		 -2.15%
(-3.24% to -1.07%)		 -46
(-94 to -31)
thrombocytopenia 30 days 27
(1.32%)		 64
(3.17%)		 -140%
(-274% to -53%)		 -1.85%
(-2.76% to -0.94%)		 -54
(-110 to -36)

tenecteplase + enoxaparin v. tenecteplase + abciximab + heparin
Outcome Time to outcome CER EER RRR
(95% CI)		 ARR
(95% CI)		 NNT
(95% CI)
death 30 days 133
(6.59%)		 109
(5.40%)		 18%
(-5% to 36%)		 1.19%
(-0.28% to 2.66%)		 84
(NNT = 340 to infinity;
NNH = 38 to infinity)
inhospital reinfarction 30 days 44
(2.18%)		 54
(2.68%)		 -23%
(-82% to 17%)		 -0.50%
(-1.45% to 0.45%)		 -200
(NNT = 69 to infinity;
NNH = 220 to infinity)
inhospital refractory ischaemia 30 days 64
(3.17%)		 93
(4.61%)		 -54%
(-99% to -6%)		 -1.44%
(-2.63% to -0.24%)		 -70
(-410 to -38)
inhospital intracranial haemorrhage 30 days 19
(0.94%)		 18
(0.89%)		 5%
(-80% to 50%)		 0.050%
(-0.54% to 0.64%)		 2000
(NNT = 190 to infinity;
NNH = 160 to infinity)
other major bleeding 30 days 87
(4.31%)		 62
(3.07%)		 29%
(2% to 48%)		 1.24%
(0.076% to 2.40%)		 81
(42 to 1300)
thrombocytopenia 30 days 64
(3.17%)		 24
(1.19%)		 63%
(40% to 76%)		 1.98%
(1.08% to 2.88%)		 50
(35 to 92)

Citation

  1. ASSENT-3 investigators , : efficacy and safety of tenecteplase in combination with enoxaparin, abciximab or unfractionated hepartin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 2001; 358 : 605-613
Search Terms: from ACP Journal Club
Contributor: Chris Ball, April 2002
Reviewer:

Clinical Question.
Patient acute myocardial infarction
Intervention or Exposure tenecteplase with enoxaparin or tenecteplase with abciximab and heparin
Comparison tenecteplase with heparin
Outcome death, reinfarction, refractory ischaemia, major bleeding, thrombocytopenia