Atrial fibrillation: warfarin reduces stroke, but increases major haemorrhage

Clinical bottom line (level 1a)

  1. Patients with atrial fibrillation who receive warfarin compared with placebo are less likely to have a stroke (NN T = 18 at months) but more likely to have a major haemorrhage (NN H = 83 at months) .
  2. There was no clear difference in mortality between the two groups.
  3. Patients with atrial fibrillation who receive aspirin compared with placebo are not clearly less likely to have a stroke, a major haemorrhage or die.
  4. Patients who receive warfarin compared with antiplatelet agents are less likely to have a stroke (NN T = 56 at months) , but are not clearly less likely to have a major bleed or die.
  5. Patients who receive warfarin compared with aspirin are less likely to have a stroke (NN T = 55 at months) , but are not clearly less likely to have a major bleed or die.
  6. Patients who take adjusted-dose warfarin compared with low-dose warfarin are less likely to have a stroke (NN T = 35 at months) , but not clearly more likely to have a major bleed or die.
  7. Patients who receive adjusted-dose warfarin compared with low-dose warfarin and aspirin are less likely to have a stroke (NN T = 21 at months) , but not clearly more likely to have a major bleed or die.
Segal et al: Cochrane Library 2001; 1 : -
Expires November 2003

The study

Systematic review of all randomised controlled trials of
  • Patients: atrial fibrillation or flutter
  • Intervention: anticoagulants (including warfarin, LMWH) compared with antiplatelet therapy (including aspirin, indobufen)
  • Outcome: stroke, major haemorrhage, death

    Articles found in English using Medline, CENTRAL, Embase, 1966 to December 1999 (search terms: ) and searching 'related articles' in Pubmed, tables of contents of recent relevant journals.

    Selection criteria: by 2 independent reviewers
    Appraisal criteria: by 2 independent reviewers: based on study population, bias and confounding, description ot therapy, outcomes and follow-up, statistical analysis and reporting
    Articles excluded if:
    • post-operative AF
    • rheumatic valvular heart disease
    • children


    14 RCTs found
    • 6 involving 2854 patients comparing warfarin with placebo
    • 5 involving 2769 patients comparing aspirin with placebo
    • 5 involving 3298 patients comparing warfarin with antiplatelet agents
    • 4 involving 2382 patients comparing warfarin with aspirin
    • 2 involving 1385 comparing adjusted-dose warfarin with low-dose warfarin and aspirin
    • 1 involving 303 patients comparing adjusted-dose warfarin with low-odse warfarin

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NN T
    (95% CI)
    warfarin v. placebo: stroke months 124/1425
    (8.7%)    		 0.34
    (0.25 to 0.46)     		18
    (16 to 22)
    warfarin v. placebo: major haemorrhage months 13/1425
    (0.91%)    		 2.35
    (1.30 to 4.24)     		83
    (35 to 370)
    warfarin v. placebo: death months 86/824
    (10.4%)    		 0.74
    (0.53 to 1.04)     		40
    (NNT = 270 to infinity;
    NNH = 22 to infinity)
    aspirin v. placebo: stroke months 155/1373
    (11.3%)    		 0.80
    (0.62 to 1.03)     		49
    (NNT = 330 to infinity;
    NNH = 25 to infinity)
    aspirin v. placebo: major haemorrhage months 18/1282
    (1.4%)    		 0.94
    (0.48 to 1.84)     		1200
    (NNT = 87 to infinity;
    NNH = 140 to infinity)
    aspirin v. placebo: death months 158/1037
    (15.2%)    		 0.87
    (0.68 to 1.12)     		58
    (NNT = 66 to infinity;
    NNH = 23 to infinity)
    warfarin v. antiplatelet agents: stroke months 18/1653
    (5.0%)    		 0.63
    (0.45 to 0.90)     		56
    (38 to 210)
    warfarin v. antiplatelet agents: major haemorrhage months 13/1653
    (0.79%)    		 1.82
    (0.95 to 3.48)     		-160
    (NNT = 53 to infinity;
    NNH = 2600 to infinity)
    warfarin v. antiplatelet agents: death months 74/1317
    (5.6%)    		 0.94
    (0.67 to 1.31)     		310
    (NNT = 62 to infinity;
    NNH = 56 to infinity)
    warfarin v. aspirin: stroke months 64/1191
    (5.4%)    		 0.65
    (0.44 to 0.97)     		55
    (34 to 650)
    warfarin v. aspirin: major haemorrhage months 12/1191
    (1.0%)    		 1.56
    (0.77 to 3.18)     		-180
    (NNT = 47 to infinity;
    NNH = 440 to infinity)
    warfarin v. aspirin: death months 39/855
    (4.6%)    		 0.95
    (0.60 to 1.50)     		460
    (NNT = 47 to infinity;
    NNH = 56 to infinity)
    adjusted-dose warfarin v. low-dose warfarin: stroke months 5/150
    (3.3%)    		 0.13
    (0.02 to 0.75)     		35
    (31 to 120)
    adjusted-dose warfarin v. low-dose warfarin: major haemorrhage months 1/150
    (0.67%)    		 3.80
    (0.76 to 19.1)     		-55
    (NNT = 9 to infinity;
    NNH = 630 to infinity)
    adjusted-dose warfarin v. low-dose warfarin: death months 7/150
    (4.7%)    		 0.83
    (0.28 to 2.53)     		130
    (NNT = 16 to infinity;
    NNH = 30 to infinity)
    adjusted-dose warfarin v. low-dose warfarin and aspirin: stroke months 54/692
    (7.80%)    		 0.38
    (0.24 to 0.60)     		21
    (17 to 34)
    adjusted-dose wafarin v. low-dose warfarin and aspirin: major haemorrhage months 14/692
    (2.0%)    		 1.14
    (0.55 to 2.36)     		-360
    (NNT = 38 to infinity;
    NNH = 110 to infinity)
    adjusted-dose warfarin v. low-dose warfarin and aspirin: death months 51/692
    (7.4%)    		 1.02
    (0.68 to 1.52)     		-730
    (NNT = 45 to infinity;
    NNH = 29 to infinity)

    • One study involving 598 patients compared aspirin with low-dose warfarin but was too small to show any difference in stroke between the two groups.
    • One study involving 916 patients compared warfarin and indobufen, but was too small to show any difference in stroke, haemorrhage or mortality between the two groups.
    • One study involving 75 patients compared LMWH and placebo, but was too small to show any difference in stroke or mortality between the two groups.

    Comments

    1. 1 non-English article was found.

    Citation

    1. Segal DB, McNamara RL, Miller MR, et al: anticoagulants or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter. Cochrane Library 2001; 1 : -
    Search Terms:
    Contributor: Chris Ball, November 2001
    Reviewer:

    Clinical Question.
    Patient atrial fibrillation
    Intervention or Exposure anticoagulants or antiplatelet therapy
    Outcome stroke, major haemorrhage, death
    		•