Unstable angina: LMWH reduced the number of episodes of recurrent angina and MI compared with unfractionated heparin.

Clinical bottom line (level 1b)

  1. LMWH and aspirin reduced recurrent angina (NNT = 4 at 7 days) , acute MI (NNT = 18 at 7 days) and revascularisation procedures (NNT = 12 at 7 days) compared with heparin and aspirin in patients with unstable angina.
  2. The effect on major bleeds was unclear.
Gurfinkel et al: Journal of the American College of Cardiology 1995; 26: 313-318
Expires July 2003

The study

Single-blinded concealed randomised trial with intention-to-treat
Setting: teaching hospital, Argentina

211 patients (aged mean 63 years, 60%% male)
  • recent onset or prolonged unstable angina and presenting with spontaneous rest pain 24 hours before randomisation
  • evidence of ischaemic heart disease (ECG ischaemic changes, previous MI, CABG, coronary angiography showing 70% or more stenosis, angina at rest without acute ECG changes, positive stress test for angina or ST segment depression in the last month)


Excluded if
  • acute/recent MI
  • left bundle branch block
  • angina caused by pulmonary oedema, post acute/subacute MI, hyperthyroidism , hypertension, anaemia
  • angioplasty in last three months
  • contraindications to anticoagulation, NSAIDs
  • already using anticoagulants
  • terminal disease
  • pregnancy
  • implanted pacemaker


    • Control Group: (n = 73, 73 analysed): saline and aspirin 200 mg daily
    Experimental Group: (n = 70, 70 analysed): unfractionated heparin (400 U/kg/day adjusted so aPTT 2.0) and aspirin
    Experimental Group: (n = 68, 68 analysed): nadroparin 214 U/kg sc twice daily and aspirin
    All patients had beta-blockers, calcium channel blockers or iv nitrates alone or in combination. Preadmission medication was continued; dosage was increased or other antianginal medication added.
    100% followed for 7 days

    The evidence

    saline and aspirin vs unfractionated heparin and aspirin
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    recurrent angina 7 days 27
    (37.0%)    		 31
    (44.3%)    		 -20%
    (-78% to 20%)    		 -7.29%
    (-23.4% to 8.78%)    		 -14
    (NNT = 11 to infinity;
    NNH = 4 to infinity)
    major bleeding 7 days 0
    (0.0%)    		 2
    (2.86%)    		 %
    (% to %)    		 -2.86%
    (-6.76% to 1.05%)    		 -35
    (NNT = 96 to infinity;
    NNH = 15 to infinity)
    acute MI 7 days 7
    (9.6%)    		 4
    (5.71%)    		 40%
    (-94% to 82%)    		 3.89%
    (-4.79% to 12.6%)    		 26
    (NNT = 8 to infinity;
    NNH = 21 to infinity)
    revascularisation 7 days 9
    (12.3%)    		 7
    (10.0%)    		 19%
    (-106% to 68%)    		 2.30%
    (-8.00% to 12.6%)    		 43
    (NNT = 8 to infinity;
    NNH = 12 to infinity)

    unfractionated heparin and aspirin vs LMWH and aspirin
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    recurrent angina 7 days 31
    (42.5%)    		 14
    (20.0%)    		 53%
    (19% to 73%)    		 22.5%
    (7.79% to 37.2%)    		 4
    (3 to 13)
    major bleeding 7 days 2
    (2.70%)    		 0
    (0.00%)    		 100%
    (% to %)    		 2.70%
    (-1.02% to 6.42%)    		 37
    (NNT = 16 to infinity;
    NNH = 98 to infinity)
    acute MI 7 days 4
    (5.50%)    		 0
    (0.00%)    		 100%
    (% to %)    		 5.50%
    (0.27% to 10.7%)    		 18
    (9 to 370)
    revascularisation 7 days 7
    (9.60%)    		 1
    (1.43%)    		 85%
    (-18% to 98%)    		 8.17%
    (0.86% to 15.5%)    		 12
    (6 to 116)

    Comments

    1. Study not large enough to show difference between aspirin alone and in combination with heparin.
    2. Physicians were unblinded to outcomes- does this explain why LMWH found to be so much better than heparin compared with other studies.
    3. Especially in centres where an invasive approach to acute coronary syndromes is favoured and where extensive utilization of intravenous glycoprotein IIb/IIIa inhibitors may occur, it remains unclear what the role of LMWH should be.
    4. Still uncertain as to the relative effiacies of the various LMWH products

    Citation

    1. Gurfinkel EP, Manos EJ, Mejail RI, et al: Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischaemia. Journal of the American College of Cardiology 1995; 26: 313-318
    Contributor: Nick Shenker and Chris Ball, July 2000
    Reviewer: Deepak L Bhatt

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