Unstable angina: hirudin decreased cardiovascular death, MI or refractory angina.

Clinical bottom line (level 1b)

  1. Patients with acute myocardial ischaemia who were given hirudin were less likely to have one of cardiovascular death, new myocardial infarction or refractory angina, than those given heparin (NNT = 88 at 7 days) .
  2. Patients given hirudin were more likely to have a major bleeding episode (NNH = 205 at 7 days) .
  3. There was no clear difference in patients who suffered either a cardiovascular death or having a new myocardial infarction.
Organisation to Assess Strategies for Ischaemic Syndromes (OASIS-2) Investigators : Lancet 1999; 353: 429-438
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: seven countries, Canada, Italy, Poland, Hungary, Greece, Mexico and Argentina

10141 patients (aged mean 64 years, 61% male) within 12 hours of an episode of chest pain suspected to be due to unstable angina or myocardial infarction without ST elevation on admission ECG

Excluded if
  • previous enrolment in this or other trials of hirudin
  • current participation in other trials
  • contraindications to heparin or hirudin
  • stroke in the previous year
  • renal impairment
  • need for long-term oral anticoagulant therapy
  • percutaneous transluminal coronary angioplasty within the previous 6 months
  • planned thrombolysis or direct percutaneous transluminal coronary angioplasty
  • pregnancy
  • <21 or >85 years old
  • cardiogenic shock
  • angina not due to coronary disease
  • other unrelated diseases that might limit life expectancy to <6 months
  • expected poor compliance


    • Control Group: (n = 5058, 5058 analysed): heparin in an initial bolus of 5000 U followed by an infusion of 15 U kg -1 h -1 plus hirudin placebo, 72 hours
    Experimental Group: (n = 5083, 5083 analysed): hirudin as an initial bolus of 0.4 mg/kg followed by an infusion of 0.15 mg kg -1 h -1 plus heparin placebo, for 72 hours
    Doses of heparin and hirudin could be adjusted, according to predefined rules, to maintain the activated partial thromboplastin time between 60 and 100 seconds.
    99.9% followed for 7 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    cardiovascular death, new myocardial infarction or refractory angina 7 days 340
    (6.72%)    		 284
    (5.59%)    		 17.0%
    (3.00% to 29.0%)    		 1.13%
    (0.20% to 2.07%)    		 88
    (48 to 501)
    major bleeding episodes 7 days 34
    (0.67%)    		 59
    (1.16%)    		 -73.0%
    (-163% to -13.0%)    		 -0.49%
    (-0.86% to -0.12%)    		 -205
    (-849 to -116)
    cardiovascular death or new myocardial infarction 7 days 213
    (4.21%)    		 182
    (3.58%)    		 15.0%
    (-3.00% to 30.0%)    		 0.63%
    (-0.12% to 1.38%)    		 159
    (NNT = 816 to infinity;
    NNH = 72 to infinity)

    Comments

    1. The marginal benefit of hirudin over heparin is less than UFH vs LMWH. There is little evidence to institute institutional change

    Citation

    1. Organisation to Assess Strategies for Ischaemic Syndromes (OASIS-2) Investigators , : Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial. Lancet 1999; 353: 429-438
    Contributor: Clare Wotton and Bob Phillips, January 2000
    Reviewer: Dwight Peretz

    Clinical Question.
    Patient myocardial ischaemia
    Intervention or Exposure hirudin
    Comparison heparin
    Outcome cardiovascular death or new myocardial infarction