Unstable angina, non-Q wave MI: aspirin reduced deaths and non-fatal myocardial infarctions.

Clinical bottom line (level 1b)

  1. Men with unstable coronary artery disease who took aspirin indefinitely were less likely to die or have a MI in the next three months (NNT = 10 at 3 months) .
  2. Using heparin either alone or in addition to aspirin did not clearly have any effect on subsequent outcome.
The RISC group : Lancet 1990; 326: 827-830
Expires June 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: eight acute hospitals, Sweden

796 patients (aged mean 58 years, 100% male) unstable coronary artery disease (defined as non-Q wave MI or increasing angina within last four weeks, associated with ischaemic changes on a resting ECG or pre discharge exercise tolerance test)

Excluded if
  • >70 years old
  • myocardial dysfunction, valvular heart disease
  • administrative difficulties
  • previous CABG
  • currently on warfarin or aspirin
  • previous inclusion
  • bleeding risk or allergy to study medication
  • non-cardiac disease
  • normal ECG or anterior Q-wave MI
  • left bundle branch block, QS complexes in = 2 adjacent chest leads, heart rate >150 on admission


    • Control Group: (n = 199, 199 analysed): placebo
    Experimental Group: (n = 189, 189 analysed): aspirin 75 mg po once daily indefinitely and placebo
    Experimental Group: (n = 198, 198 analysed): heparin 5000 units every 6 hours for 5 days, and placebo
    Experimental Group: (n = 210, 210 analysed): heparin and aspirin
    All patients without contraindications received metoprolol 100-200 mg po once daily. Chest pain was treated with nitrates and calcium antagonists as necessary.
    100% followed for 3 months
    Outcome notes:
    • death or MI : MI defined as two of: severe chest pain of long duration, a diagnostic ECG, or increase in cardiac enzymes above upper reference level

    The evidence

    aspirin vs placebo
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death or MI 3 months 35
    (17.6%)    		 14
    (7.41%)    		 58%
    (24% to 77%)    		 10.2%
    (3.71% to 16.7%)    		 10
    (6 to 27)

    heparin vs placebo
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death or MI 3 months 35
    (17.6%)    		 33
    (16.7%)    		 5%
    (-46% to 39%)    		 0.92%
    (-6.49% to 8.33%)    		 110
    (NNT = 12 to infinity;
    NNH = 15 to infinity)

    heparin plus aspirin vs placebo
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death or MI 3 months 35
    (17.6%)    		 12
    (5.71%)    		 68%
    (39% to 83%)    		 11.9%
    (5.72% to 18.0%)    		 8
    (6 to 17)

  • No significant differences were noted between the groups for the number of revascularisations required.

    • Comments

    1. Note there was a mean treatment delay of 33 hours, and 81% of patients began treatment more than 24 hours after admission.
    2. Other studies have shown that heparin combined with aspirin reduces MI and death at six days compared with aspirin alone. LMWH has been shown to be more effective than heparin.

    Citation

    1. The RISC group , : Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet 1990; 326: 827-830
    Search Terms: angin* in Cochrane
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: William Rhoton

    Clinical Question.
    Patient unstable coronary artery disease
    Intervention or Exposure aspirin, heparin or both
    Comparison placebo
    Outcome death of non-fatal MI