Anticoagulation: more strokes and bleeds occurred when INR was 5.0 or more.

Clinical bottom line (level 2b)

  1. A sixth of patients with atrial fibrillation on oral anticoagulation had an ischaemic event or major bleed.
  2. Patients with atrial fibrillation on warfarin, were at increased risk of an ischaemic event or major bleed if their INR = 5.0 (NNF = 2 for 2 years) .
  3. Patients with cardiothoracic ratio >50% (NNT = at years) were also at an increased risk.
The European Atrial Fibrillation Study Group : New England Journal of Medicine 1995; 333 (1): 5-10
Expires June 2003

The study

Inception cohort study with objective outcomes, adjusted for confounding factors, not validated in an independent set of patients.

Setting: 96 acute hospitals, Europe

214 patients (aged mean 71 years, 55% male) on oral anticoagulation for non-rheumatic atrial fibrillation and a recent minor cerebral ischaemic event.

Factors studied:
  • death, ischaemic events, major bleeds
  • INR 2.0 to 2.9
  • INR 3.0 to 3.9
  • INR 4.0 to 4.9
  • INR = 5.0
  • age >75
  • systolic blood pressure >160 mmHg
  • ischaemic heart disease
  • cardiothoracic ratio >50%


    • Patients received acenocoumarol, fenprocoumarin or warfarin- INR titred to 2.5 to 3.9 (checked monthly).

    Multivariate regression analysis was used to adjust for associated risk factors- age, systolic blood pressure, history of ischaemic heart disease, cardiomegaly (cardiothoracic ratio >50% on PA chest x-ray).

    100% followed for 2.1 years
    Outcomes studied:
  • death
  • ischaemic events
  • major bleed patients admitted to hospital, transfused or required surgery
  • ischaemic events and major bleeds

    • Data was taken from a randomised controlled trial.

    The evidence

    outcome time to outcome number of patients/total number %
    (95% CI)
    death 2.1 years 9/214 4.21%
    (1.52% to 6.89%)
    ischaemic events 2.1 years 25/214 11.7%
    (7.38% to 16.0%)
    major bleed 2.1 years 13/214 6.07%
    (2.87% to 9.28%)
    ischaemic events and major bleeds 2.1 years 38/214 17.8%
    (12.6% to 22.9%)

    prognostic factor for
    ischaemic events and major bleeds     		time to outcome adjusted RR
    (95% CI)    		 NNF+
    (95% CI)
    INR 2.0 to 2.9 2.1 years
    ( to )     		-7
    (-14 to -6)
    INR 3.0 to 3.9 2.1 years 0.4
    (0.1 to 1.1)     		-9
    (-6 to 56)
    INR 4.0 to 4.9 2.1 years 1.6
    (0.6 to 4.6)     		9
    (-14 to 2)
    INR = 5.0 2.1 years 3.6
    (1.2 to 11)     		2
    (1 to 28)
    age >75 2.1 years 3.1
    (1.5 to 6.4)     		3
    (1 to 11)
    systolic blood pressure >160 mmHg 2.1 years 1.6
    (0.6 to 3.9)     		9
    (-14 to 2)
    ischaemic heart disease 2.1 years 1.4
    (0.6 to 3.4)     		14
    (-14 to 2)
    cardiothoracic ratio >50% 2.1 years 2.9
    (1.4 to 5.9)     		3
    (1 to 14)

    • INR in range 56% of times measured; supratherapeutic 9%.

    Citation

    1. The European Atrial Fibrillation Study Group , : Optimal oral anticoagulant therapy in patients with non rheumatic atrial fibrillation and recent cerebral ischemia. New England Journal of Medicine 1995; 333 (1): 5-10
    Search Terms: atrial fibr* in Cochrane
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: William Rhoton

    Clinical Question.
    Patient on anticoagulation for atrial fibrillation and minor ischaemic event
    Intervention or Exposure INR levels
    Outcome death, stroke, systemic embolism, MI or major bleed