Atrial fibrillation: fewer strokes on adjusted-dose warfarin than fixed dose plus aspirin.

Clinical bottom line (level 1b)

  1. Patients with atrial fibrillation at high risk for stroke had fewer ischaemic strokes on adjusted-dose warfarin than fixed-dose plus aspirin (NNT = 16 at 12 months) . They also had fewer disabling strokes (NNT = 25 at 12 months) .
  2. The effect on mortality and bleeding complications was unclear.
  3. Around 2.5% of patients had a major bleed, and 1% an intracranial haemorrhage at one year.
Stroke Prevention in Atrial Fibrillation Investigators : Lancet 1996; 348: 633-638
Expires June 2003

The study

Unblinded concealed randomised trial with intention-to-treat
Setting: twenty centres, USA

1044 patients (aged mean 72 years, 61% male) non-valvular atrial fibrillation (84% constant) within the last six months, documented by ECG and one or more high risk features for a stroke
  • impaired left ventricular function (CCF within 100 days or fractional shortening on echo 25% or less
  • systolic blood pressure >160 mmHg
  • prior ischaemic stroke, TIA or systemic embolism >30 days before study entry
  • female aged >75


Excluded if
  • mitral stenosis or prosthetic heart valves, or condition requiring anticoagulation (eg. PE)
  • contraindication to aspirin 325 mg/day
  • contraindication to warfarin (previous intracranial bleed, GI bleed within 6 months, previous severe haemorrhage on warfarin with therapeutic INR, severe alcohol habituation, pre-treatment INR>1.2, regular use of NSAIDs)


    • Control Group: (n = 523, 523 analysed): warfarin adjusted so INR 2.0-3.0
    Experimental Group: (n = 521, 521 analysed): aspirin 325 mg/day and low-intensity warfarin 0.5 to 3.0 mg/day (based on two measurements a week apart to raise INR to 1.2 to 1.5)

    100% followed for 12 months
    Outcome notes:
    • ischaemic stroke or systemic emboli : stroke- sudden neurological deficit lasting >24 hours, with primary haemorrhage; systemic emboli- abrupt vascular insufficiency from arterial occlusion
    • disabling/fatal stroke : disabling stroke-restriction in lifestyle, not preventing independent existence
    • major haemorrhage : fall in Hb >2 g/dl, intracranial bleed, retroperitoneal bleed or transfusion

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNH
    (95% CI)
    treatment withdrawal 12 months 30
    (5.74%)    		 43
    (8.25%)    		 -44%
    (-126% to 8%)    		 -2.52%
    (-5.61% to 0.57%)    		 40
    (NNT = 174 to infinity;
    NNH = 18 to infinity)
    death 12 months 35
    (6.69%)    		 42
    (8.06%)    		 -20%
    (-86% to 22%)    		 -1.37%
    (-4.54% to 1.80%)    		 -73
    (NNT = 56 to infinity;
    NNH = 22 to infinity)
    ischaemic stroke or systemic emboli 12 months 11
    (2.10%)    		 44
    (8.45%)    		 -302%
    (-669% to -110%)    		 -6.34%
    (-9.03% to -3.66%)    		 16
    (11 to 27)
    disabling/fatal stroke 12 months 10
    (1.91%)    		 31
    (5.95%)    		 -211%
    (-528% to -54%)    		 -4.04%
    (-6.38% to -1.69%)    		 25
    (16 to 59)
    major haemorrhage 12 months 12
    (2.29%)    		 13
    (2.50%)    		 -9%
    (-136% to 50%)    		 -0.20%
    (-2.06% to 1.65%)    		 500
    (NNT = 60 to infinity;
    NNH = 49 to infinity)
    intracranial bleed 12 months 3
    (0.57%)    		 5
    (0.96%)    		 -67%
    (-596% to 60%)    		 -0.39%
    (-1.44% to 0.67%)    		 26-
    (NNT = 150 to infinity;
    NNH = 69 to infinity)

    Comments

    1. Study was not large enough to comment on the effect on major haemorrhage, death or treatment withdrawal.

    Citation

    1. Stroke Prevention in Atrial Fibrillation Investigators , : Adjusted-dose warfarin versus low intensity fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation. Lancet 1996; 348: 633-638
    Search Terms: atrial fibr* and anticoag* in Cochrane
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer:

    Clinical Question.
    Patient non-valvular atrial fibrillation
    Intervention or Exposure aspirin and low-intensity warfarin
    Comparison warfarin
    Outcome death, stroke