Unstable angina: moderate intensity warfarin decreases rehospitalisation with unstable angina.

Clinical bottom line (level 1b)

  1. Patients with unstable angina who were given moderate intensity warfarin treatment were less likely to be rehospitalised with unstable angina (NNT = 10 at 3 months) .
  2. Patients who were given low intensity warfarin treatment had no clear difference in primary outcome events.
  3. Patients given moderate intensity warfarin treatment had no clear difference in primary outcome events.
Anand et al: Circulation 1998; 98: 1064-1070
Expires March 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 31 clinical centres, Canada

506 patients (aged mean 64 years, 67% male) Admitted to hospital within 12 hours of an episode of chest pain suspected to be due to unstable angina or myocardial infarction without ST elevation on their admission ECG.

Excluded if
  • suffered major bleeding on or within 48 hours of the initial intravenous infusion
  • clear clinical indication for warfarin treatment
  • coronary artery bypass grafting planned before or within one week of hospital discharge


    • Control Group: (n = 253, 253 analysed): Phase 1: fixed dose of warfarin , 3 mg (target international normalised ratio, INR, 1.5)to achieve a low-density level of anticoagulation, for 180 days (154 patients). Phase 2: moderate-intensity anticoagulation (target INR 2-2.5), for three months (99 patients).
    Experimental Group: (n = 253, 253 analysed): Phase 1: standard therapy for 180 days (155 patients). Phase 2: standard therapy for 3 months (98 patients).
    Patients were initially randomised to heparin or hirudin. Warfarin treatment was started 5 to 7 days after the heparin or hirudin. Aspirin treatment was advised for all participants.
    100% followed for 6 months
    Outcome notes:
    • low intensity warfarin: primary outcome event : cardiovascular death, new myocardial infarction or refractory angina
    • moderate intensity warfarin: primary outcome event : cardiovascular death, new myocardial infarction or refractory angina

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    moderate intensity warfarin: rehospitalised for unstable angina 3 months 17
    (17.2%)    		 7
    (7.14%)    		 58.0%
    (4.00% to 82.0%)    		 10.0%
    (1.02% to 19.0%)    		 10
    (5 to 98)
    low intensity warfarin: primary outcome event 6 months 6
    (3.90%)    		 10
    (6.45%)    		 -66.0%
    (-344% to 38.0%)    		 -2.56%
    (-7.48% to 2.37%)    		 -39
    (NNT = 42 to infinity;
    NNH = 13 to infinity)
    moderate intensity warfarin: primary outcome event 3 months 12
    (12.1%)    		 5
    (5.10%)    		 58.0%
    (-15.0% to 85.0%)    		 7.02%
    (-0.75% to 14.8%)    		 14
    (NNT = 7 to infinity;
    NNH = 134 to infinity)

    Comments

    1. 45 (29%) patients taking warfarin discontinued therapy before the end of the six month follow-up.
    2. Does adding moderate-intensity warfarin to antiplatelet, statin and ACE-I really increase overall patient wellbeing?

    Citation

    1. Anand SS, Yusuf S, Pogue J, et al: Long-term oral anticoagulant therapy in patients with unstable angina or suspected non-Q-wave myocardial infarction: Organization to assess strategies for ischemic syndromes (OASIS) pilot study results. Circulation 1998; 98: 1064-1070
    Contributor: Clare Wotton and Bob Phillips, January 2000
    Reviewer: Timo Strandberg

    Clinical Question.
    Patient acute ischaemic syndromes
    Intervention or Exposure long-term anticoagulation
    Comparison standard treatment
    Outcome recurrent ischaemic events