Acute coronary syndrome: short-term heparin or LMWH reduces death and myocardial infarction, but long-term LMWH increases major haemorrhage

Clinical bottom line (level 1a)

  1. Patients with an acute coronary syndrome and no ST elevation treated with aspirin who receive heparin or LMWH compared with placebo or control are less likely to die or have a myocardial infarction (NNT = 30 at 7 days) .
  2. Patients on short-term heparin or LMWH are not clearly more likely to have a major haemorrhage, nor less likely to develop recurrent angina or require revascularisation.
  3. Patients given LMWH compared with heparin are not clearly less likely to die or have a myocardial infarction, nor clearly more likely to have a major haemorrhage.
  4. Patients with an acute coronary syndrome without ST elevation treated with aspirin, who received long-term LMWH compared with placebo, are at increased risk of a major haemorrhage, but are not clearly less to die or have a myocardial infarction.
Eikelboom et al: Lancet 2000; 355 : 1936-1942
Expires February 2004

The study

Systematic review of all randomised controlled trials of
  • Patients: acute coronary syndrome without ST elevation
  • Intervention: heparin, LMWH compared with placebo or heparin
  • Outcome: myocardial infarction, death, major haemorrhage, recurrent angina, need for revascularisation
Articles found in ?all languages using Medline, Embase, to 2000 (search terms: keywords relating to heparin and acute coronary syndrome without ST elevation) and and scanning reference lists of selected articles, and contacting experts in the field for unpublished results

Selection criteria: see above and below
Appraisal criteria: randomisation
Articles excluded if:
  • patients not given aspirin
  • studies comparing heparin and aspirin
  • heparin and aspirin v. combined antiplatelet therapy
  • heparin .v non-aspirin control
  • dose-ranging uncontrolled study
  • unclear or quasi-randomisation


12 studies found involving 17157 patients
  • 6 comparing heparin and placebo or untreated control: 1353 patients
  • 2 comparing LMWH and placebo or untreated control: 1639 patients
  • 5 comparing LMWH and unfractionated heparin: 12171 patients
  • 5 comparing long-term LMWH with placebo: 12099 patients

Studies were not found to be heterogeneous.

The evidence

Outcome Time to outcome CER OR
(95% CI)		 NNT
(95% CI)
LMWH or heparin v. control: death or myocardial infarction 7 days 104/1412
(7.4%)		 0.53
(0.38 to 0.73) 		30
(23 to 53)
LMWH v. heparin: death or myocardial infarction 7 days 128/5475
(2.3%)		 0.88
(0.69 to 1.12) 		360
(NNT = 140 to infinity;
NNH = 370 to infinity)
long-term LMWH v. control: death or myocardial infarction 3 months 257/6646
(3.9%)		 0.98
(0.81 to 1.17) 		1300
(NNT = 140 to infinity;
NNH = 160 to infinity)
long-term LMWH v. control: major haemorrhage 3 months /
(%)		 2.26
(1.63 to 3.14)

  • Short-term unfractionated heparin was not clearly better than control at reducing the incidence of recurrent angina, need for revascularisation, nor at increasing the incidence of major bleeding.
  • Short-term LMWH did not clearly increase major bleeding compared with control.
  • Short-term LMWH did not clearly increase major bleeding compared with heparin.
  • Long-term LMWH (> 7 days) was not clearly more effective than placebo at reducing recurrent angina or need for revascularisation.

Comments

  1. No control rate for major bleeding on long-term LMWH was reported, so no NNH could be calculated.

Citation

  1. Eikelboom JW, Anand SS, Malmberg K, et al: unfractionated heparin and low-molecular weight heparin in acute coronary syndrome without ST elevation: a meta-analysis. Lancet 2000; 355 : 1936-1942
Search Terms: from ACP Journal Club
Contributor: Chris Ball, February 2002
Reviewer:

Clinical Question.
Patient acute coronary syndrome without ST elevation
Intervention or Exposure heparin or LMWH
Outcome death, myocardial infarction, major haemorrhage