Unstable angina: LMWH reduced death and MI compared with placebo.

Clinical bottom line (level 1b)

  1. 150 days after a bout of unstable angina, about 5% of patients were dead, about 12% have a myocardial infarction, and about 30% had undergone a revascularisation procedure.
  2. LMWH reduced death, MI or revascularisation procedures compared with placebo in patients with unstable angina up to 40 days after the initial attack (NNT = 18 at 40 days) and maybe beyond.
  3. LMWH reduced MI up to 40 days in patients with unstable angina (NNT = 35 at 40 days) and maybe beyond.
Fragmin during Instability in Coronary Artery Disease (FRISC) study group : Lancet 1996; 347: 561-568
Expires July 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 23 hospitals, Sweden

1506 patients (aged mean 70 years, 60% male) admitted to hospital with chest pain in previous 72 hours, newly developed/ increasing angina pectoris/angina at rest in the last two months or persisting chest pain with a clinically suspected MI and transient/persistent ST depression of 0.1 mV and T wave inversion of 0.1 mV in two adjacent leads and no pathological Q waves in the ischaemic leads

Excluded if
  • increased risk of bleeding- cerebral bleed within 3 months, ulcer disease or known GI bleed within last 5 years, surgery in last week, eye, ear or CNS surgery in last month, known haemostatic disorder, plt <100
  • left bundle branch block or pacemaker
  • uncontrolled hypertension/hypotension
  • pathological Q waves, or Q waves in same leads as ST changes
  • indications for thrombolysis
  • PTCA or CABG planned or done in last 2 months
  • contraindications to anticoagulation, NSAIDs
  • already using anticoagulants
  • anaemia: men <12.5; women <11.0, Cr >200, PT >50% normal
  • temperature >39 ° C
  • other serious disease


    • Control Group: (n = 760, 757 analysed): placebo for 41-46 days
    Experimental Group: (n = 746, 741 analysed): dalteparin 120 U/kg (max 10000 units) subcutaneously twice daily for 6 days then 7500 units daily for 35-40 days
    All patients had aspirin 75 mg (initially 300 mg) and beta-blocker, with nitrates, calcium channel blockers and glyceryl trinitrate as required.
    99% followed for 150 days
    Outcome notes:
    • death, MI or revascularisation : MI defined as two of: prolonged chest pain; diagnostic ECG, raised biochemical markers. Revascularisation (coronary angioplasty) performed in patients with disabling angina despite medical therapy, or patients with signs of silent ischaemia on pre discharge exercise testing

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death, MI or revascularisation 6 days 43
    (5.68%)    		 16
    (2.16%)    		 62%
    (33% to 78%)    		 3.52%
    (1.57% to 5.47%)    		 28
    (18 to 64)
    death 6 days 8
    (1.06%)    		 7
    (0.94%)    		 11%
    (-145% to 67%)    		 0.11%
    (-0.90% to 1.12%)    		 900
    (NNT = 89 to infinity;
    NNH = 110 to infinity)
    MI 6 days 33
    (4.36%)    		 10
    (1.35%)    		 69%
    (38% to 85%)    		 3.01%
    (1.33% to 4.68%)    		 33
    (21 to 75)
    revascularisation 6 days 9
    (1.19%)    		 3
    (0.40%)    		 66%
    (-25% to 91%)    		 0.78%
    (-0.11% to 1.68%)    		 130
    (NNT = 59 to infinity;
    NNH = 880 to infinity)
    death, MI, revascularisation 40 days 179
    (23.7%)    		 133
    (18.0%)    		 24%
    (7% to 38%)    		 5.70%
    (1.60% to 9.80%)    		 18
    (10 to 63)
    death 40 days 23
    (3.04%)    		 19
    (2.56%)    		 16%
    (-54% to 54%)    		 0.47%
    (-1.20% to 2.14%)    		 210
    (NNT = 47 to infinity;
    NNH = 84 to infinity)
    MI 40 days 72
    (9.51%)    		 49
    (6.61%)    		 30%
    (1% to 51%)    		 2.90%
    (0.15% to 5.65%)    		 35
    (18 to 680)
    revascularisation 40 days 114
    (15.1%)    		 87
    (11.7%)    		 22%
    (-1% to 40%)    		 3.32%
    (-0.13% to 6.76%)    		 30
    (NNT = 15 to infinity;
    NNH = 800 to infinity)
    death, MI, revascularisation 150 days 326
    (43.1%)    		 296
    (40.0%)    		 7%
    (-5% to 18%)    		 3.12%
    (-1.87% to 8.11%)    		 32
    (NNT = 12 to infinity;
    NNH = 53 to infinity)
    death 150 days 41
    (5.42%)    		 39
    (5.26%)    		 3%
    (-49% to 37%)    		 0.15%
    (-2.12% to 2.43%)    		 650
    (NNT = 41 to infinity;
    NNH = 47 to infinity)
    MI 150 days 98
    (13.0%)    		 83
    (11.2%)    		 13%
    (-14% to 34%)    		 1.74%
    (-1.55% to 5.04%)    		 57
    (NNT = 20 to infinity;
    NNH = 64 to infinity)
    revascularisation 150 days 254
    (33.6%)    		 229
    (30.9%)    		 8%
    (-7% to 20%)    		 2.65%
    (-2.08% to 7.38%)    		 38
    (NNT = 14 to infinity;
    NNH = 48 to infinity)

    Comments

    1. A subgroup analysis showed smokers had less benefit from LMWH. This subgroup analysis was not initially planned, and may reflect a data-dependent effect.

    Citation

    1. Fragmin during Instability in Coronary Artery Disease (FRISC) study group , : Low-molecular-weight heparin during instability in coronary artery disease. Lancet 1996; 347: 561-568
    Search Terms: handsearch
    Contributor: Chris Ball and Clare Wotton, July 2000
    Reviewer: Dwight Peretz

    Clinical Question.
    Patient unstable angina
    Intervention or Exposure LMWH
    Outcome death, pain, revascularisation, MI