Unstable angina: enoxaparin was not clearly better than unfractionated heparin.

Clinical bottom line (level 1b-)

  1. Patients with unstable angina or non-Q-wave MI who were given enoxaparin, had no clear difference in death, MI or urgent revascularisation at 14 days than those given unfractionated heparin, but there was a trend towards less of these endpoints with enoxaparin.
  2. Patients given enoxaparin were more likely to suffer a minor or major haemorrhage than those given unfractionated heparin. (NNH = 14 at 8 days)
Antman et al: Circulation 1999; 100: 1593-1601
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 200 centres, 10 countries in North America, South America and Europe

3910 patients (aged quartiles 56 to 73 years; median 66, 65% male) Unstable angina or non-Q-wave myocardial infarction. History of coronary artery disease with ST deviation or elevated serum cardiac markers.

Excluded if
  • planned revascularisation within 24 hours
  • treatable cause of angina
  • evolving Q-wave MI
  • history of coronary artery bypass grafting surgery within 2 months or percutaneous transluminal coronary angioplasty within 6 months
  • treatment with continuous infusion of unfractionated heparin for >24 hours before enrolment
  • history of heparin-associated thrombocytopenia with or without thrombosis
  • contraindications to anticoagulation


    • Control Group: (n = 1957, 1957 analysed): iv unfractionated heparin for 3 days or more in a bolus of 70 U/kg and an initial infusion of 15 U/kg/hour, followed by subcutaneous placebo injections
    Experimental Group: (n = 1953, 1953 analysed): enoxaparin 30 mg iv bolus followed by injections of 1.0 mg/kg every 12 hours during the acute phase and injections every 12 hours of 40 mg-60 mg (depending on weight) during the outpatient phase
    All patients received aspirin 100-325 mg/d.
    100% followed for 43 days
    Outcome notes:
    • major or minor haemorrhage : at end of initial hospitalisation

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death, myocardial infarction or urgent revascularisation 43 days 385
    (19.7%)    		 337
    (17.3%)    		 12.0%
    (0.00% to 23.0%)    		 2.42%
    (-0.01% to 4.85%)    		 41
    (NNT = 7296 to infinity;
    NNH = 21 to infinity)
    major or minor haemorrhage 8 days 67
    (3.46%)    		 205
    (10.6%)    		 -206%
    (-300% to -134%)    		 -7.12%
    (-8.71% to -5.52%)    		 -14
    (-18 to -11)

    Comments

    1. With the results of other studies, there appears to be a significant advantage of low molecular weight heparins (e.g. enoxaparin) in unstable angina.

    Citation

    1. Antman EM, McCabe CH, Gurfinkel EP, et al: Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI) IIB trial. Circulation 1999; 100: 1593-1601
    Contributor: Clare Wotton and Bob Phillips, February 2000
    Reviewer: Dwight Peretz

    Clinical Question.
    Patient unstable angina or non-Q-wave MI
    Intervention or Exposure unfractionated heparin
    Comparison LMWH, enoxaparin
    Outcome death, MI or urgent revascularisation