Unstable angina: heparin prevented more myocardial infarctions than aspirin.

Clinical bottom line (level 1b)

  1. Heparin was better than aspirin at preventing MI in patients with unstable angina (NNT = 35 at 6 days) .
Theroux et al: Circulation 1993; 88 (1): 2045-2048
Expires July 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: two university hospitals, Canada

484 patients (aged mean 58 years, 75% male) unstable angina or non Q-wave myocardial infarction (defined as accelerating chest pain at rest or with exertion for at least 20 minutes, and ECG changes compatible with ischaemia)

Excluded if
  • taking aspirin (50% of exclusions) or other anti-platelet drugs regularly
  • previous CABG within 12 months
  • coronary angioplasty within 6 months
  • contraindication to aspirin or heparin
  • angina caused by extra-cardiac condition
  • refusal of arteriography


    • Control Group: (n = 244, 244 analysed): aspirin (650 mg loading and then 325 mg twice daily)
    Experimental Group: (n = 240, 240 analysed): heparin iv (5000 unit bolus and then 1000 units per hour, adjusted so aPTT 1.5 to 2.0)
    Medications started as soon as possible after patients had entered ER. Other treatments were discretionary. Study drug was terminated when outcome decided (usually after arteriography)- average 5.7 days. In the later stages of the study, all patients started aspirin 325 mg 12 hours before discontinuing medication.
    100% followed for 6 days
    Outcome notes:
    • myocardial infarction : three of: typical chest pain unrelieved by nitroglycerin and lasting 30 minutes or more; new ST changes or Q-waves; increase in CK levels to tow times upper limit of normal, with abnormally high CK-MB fraction

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    myocardial infarction 6 days 9
    (3.69%)    		 2
    (0.83%)    		 77%
    (-3% to 95%)    		 2.86%
    (0.23% to 5.48%)    		 35
    (18 to 440)

    Comments

    1. Continuation of a study that compared heparin, aspirin, heparin and aspirin and placebo.
    2. Short follow-up period. Note very wide confidence intervals due to small number of events.
    3. No studies have shown a benefit for combining aspirin with heparin- all have been too small to show small benefit. However, LMWH combined with aspirin does appear better than aspirin alone.

    Citation

    1. Theroux P, Waters D, Qiu S, et al: Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation 1993; 88 (1): 2045-2048
    Contributor: Nick Shenker and Chris Ball, July 2000
    Reviewer: Kenneth Ballew

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