Stroke: indobufen was not clearly better than warfarin.

Clinical bottom line (level 1b-)

  1. Patients with nonrheumatic atrial fibrillation and a history of stroke who were given indobufen, had no clear difference in vascular events, recurrent stroke or adverse effects than those given warfarin.
  2. Patients given warfarin were more likely to bleed (NNT = 23 at 12 months) .
Morocutti et al: Stroke 1997; 28: 1015-1021
Expires October 2002

The study

Unblinded ?concealed randomised trial with intention-to-treat
Setting: 80 centres, Italy

916 patients (aged mean 73 years, 53% female) chronic or paroxysmal nonrheumatic atrial fibrillation (diagnosed on at least two ECGs during the three weeks before the study), and a transient ischaemic attack or ischaemic stroke in previous three weeks

Excluded if
  • severe involutive cerebral disease
  • presence of carotid lesion requiring surgical intervention
  • need for chronic anticoagulation
  • contraindication to study drugs
  • severe renal or hepatic insufficiency
  • life expectancy less than 12 months
  • carotid endarterectomy coronary or peripheral revascularisation procedures during previous six months
  • severe arterial hypertension poorly controlled by drugs
  • acquired or congenital valvular disease (except mitral valve prolapse or mitral annulus calcification)
  • cerebral haemorrhage
  • arteriovenous malformation or tumour
  • prosthetic valves
  • acute myocardial infarction or unstable angina during previous month
  • ECG evidence of intracardiac thrombosis or tumour
  • left ventricular aneurysm
  • severe congestive heart failure (NYHA >3)
  • undergone cardioversion during the two weeks before the qualifying event
  • <31 years old


    • Note:
  • Randomisation was stratified according to centre, and assigned in groups of four.


    • Control Group: (n = 454, 447 analysed): warfarin - adjusted to INR 2.0 to 3.5, for 12 months
    Experimental Group: (n = 462, 460 analysed): indobufen - 200 mg twice daily orally, lowered to 100 mg in patients with impaired renal function, for 12 months

    99% followed for ?
    Outcome notes:
    • vascular events : nonfatal stroke, nonfatal MI, nonfatal embolism, vascular death
    • adverse effects : stomach pain, nausea, vomiting, bleeding complications
    • bleeding : major or minor

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    vascular events 12 months 41
    (9.03%)    		 49
    (10.6%)    		 -17%
    (-74% to 21%)    		 -1.58%
    (-5.43% to 2.28%)    		 -63
    (NNT = 44 to infinity;
    NNH = 18 to infinity)
    recurrent stroke 12 months 18
    (3.96%)    		 23
    (4.98%)    		 -26%
    (-129% to 31%)    		 -1.01%
    (-3.69% to 1.66%)    		 -99
    (NNT = 60 to infinity;
    NNH = 27 to infinity)
    adverse effects 12 months 33
    (7.27%)    		 21
    (4.55%)    		 37%
    (-6% to 63%)    		 2.72%
    (-0.33% to 5.77%)    		 37
    (NNT = 17 to infinity;
    NNH = 310 to infinity)
    bleeding 12 months 23
    (5.07%)    		 3
    (0.65%)    		 87%
    (58% to 96%)    		 4.42%
    (2.27% to 6.56%)    		 23
    (15 to 44)

    Citation

    1. Morocutti C, Amabile G, Fattapposta F, et al: Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. Stroke 1997; 28: 1015-1021
    Contributor: Clare Wotton and Musab Hayatli, October 2000
    Reviewer:

    Clinical Question.
    Patient nonrheumatic atrial fibrillation and stroke
    Intervention or Exposure indobufen
    Comparison warfarin
    Outcome recurrent major vascular events