Unstable angina: heparin and aspirin may be better than aspirin alone.

Clinical bottom line (level 1a-)

  1. Heparin with aspirin probably reduces the risk of MI or death or recurrent angina more than aspirin alone in patients with unstable angina or non Q-wave MI, but there was no clear difference.
  2. The effect on bleeding or revascularisation procedures is unclear.
Oler et al: Journal of the American Medical Association 1996; 276 (10): 811-815
Expires July 2003

The study

Systematic review of randomised controlled trials of
  • Patients: unstable angina or non Q-wave myocardial infarction
  • Intervention: iv heparin and aspirin compared with aspirin alone
  • Outcome: MI or death


    • Articles found in all using MEDLINE, 1966 to 1995 (search terms: heparin, aspirin and unstable angina ) and bibliographies were also searched, authors and experts contacted for unpublished studies or other relevant articles

    Selection criteria: as above
    Appraisal criteria: selected by two independent blinded reviewers using set criteria (detailed in text)
    Articles excluded if: evolving Q-wave MI on admission, CABG within 12 months, contraindication to aspirin or anticoagulation, already anticoagulated

    Six studies were found including 1353 patients (two double-blind, two single-blind)
    • Patients typically received continuous infusion of heparin so aPTT in range 1.5 to 2.0; received for 2-7 days. Aspirin dose: 75 mg to 325 mg po once daily indefinitely.
    Not significantly heterogeneous except for recurrent ischaemia pain.

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NNT
    (95% CI)
    MI or death 2-12 weeks 68/655
    (10.3%)    		 0.67
    (0.44 to 1.02)     		31
    (NNT = 18 to infinity;
    NNH = 540 to infinity)
    recurrence of ischaemic pain 12 weeks 98/434
    (22.6%)    		 0.68
    (0.40 to 1.17)     		17
    (NNT = 8 to infinity;
    NNH = 35 to infinity)
    CABG or PTCA 12 weeks 109/466
    (23.4%)    		 1.03
    (0.84 to 1.43)     		-190
    (NNT = 42 to infinity;
    NNH = 14 to infinity)
    major bleed 12 weeks 3/655
    (0.46%)    		 1.89
    (0.66 to 5.38)     		-250
    (NNT = 640 to infinity;
    NNH = 51 to infinity)

    Comments

    1. Studies were too small to demonstrate small potential benefit.
    2. LMWH and aspirin together have been shown to be more beneficial than aspirin alone; it would be likely UFH followed the same path.

    Citation

    1. Oler A, Whooley MA, Oler J, et al: Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina: a meta-analysis. Journal of the American Medical Association 1996; 276 (10): 811-815
    Search Terms: unstable angina in Cochrane
    Contributor: Chris Ball and Clare Wotton, July 2000
    Reviewer: Dwight Peretz

    Clinical Question.
    Patient unstable angina
    Intervention or Exposure aspirin and heparin
    Comparison aspirin alone
    Outcome death or MI