Anticoagulants or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter.
BACKGROUND
Atrial fibrillation (AF) carries a high risk of stroke and other thromboembolic events. Appropriate use of drugs to prevent thromboembolism in patients with AF involves comparing the patient's risk of stroke to the risk of hemorrhage from medication use.


OBJECTIVE
To quantify risk of stroke, major hemorrhage and death from using medications that have been rigorously evaluated for prevention of thromboembolism in AF.


METHODS
Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until December 1999.


METHODS
Included Randomized controlled trials of drugs to prevent thromboembolism in adults with non-postoperative AF. Excluded RCTS of patients with rheumatic valvular disease.


METHODS
Data were abstracted by two reviewers. Odds ratios from all qualitatively similar studies were combined, with weighting by study size, to yield aggregate odds ratios for stroke, major hemorrhage, and death for each drug.


RESULTS
Fourteen articles were included in this review. Warfarin was more efficacious than placebo for primary stroke prevention [aggregate odds ratio (OR) of stroke=0.30 [95% Confidence Interval (C.I.) 0.19,0.48]], with moderate evidence of more major bleeding [ OR= 1.90 [95% C.I. 0.89,4.04].]. Aspirin was inconclusively more efficacious than placebo for stroke prevention [OR=0.68 [95% C.I. 0.29,1.57]], with inconclusive evidence regarding more major bleeds [OR=0.81[95% C.I. 0.37,1.78]]. For primary prevention, assuming a baseline risk of 45 strokes per 1000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was moderate evidence for fewer strokes among patients on warfarin than on aspirin [aggregate OR=0.64[95% C.I. 0.43,0.96]], with only suggestive evidence for more major hemorrhage [OR =1.58 [95% C.I. 0.76,3.27]]. However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared to aspirin was low (5.5 per 1000 person-years) compared to an older group (15 per 1000 person-years). Low-dose warfarin or low-dose warfarin with aspirin was less efficacious for stroke prevention than adjusted-dose warfarin.


CONCLUSIONS
The evidence strongly supports warfarin in AF for patients at average or greater risk of stroke, although clearly there is a risk of hemorrhage. Although not definitively supported by the evidence, aspirin may prove to be useful for stroke prevention in sub-groups with a low risk of stroke, with less risk of hemorrhage than with warfarin. Further studies are needed of low- molecular weight heparin and aspirin in lower risk patients.
Segal
J B
JB
Medicine, Johns Hopkins School of Medicine, 1830 E. Monument St. 8th floor, Baltimore, Maryland 21205, USA. jsegal@welch.jhu.edu
McNamara
R L
RL
Miller
M R
MR
Powe
N R
NR
Goodman
S N
SN
Robinson
K A
KA
Bass
E B
EB
D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D001282:Atrial Flutter / Q000150:complications*; D016001:Confidence Intervals; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors