A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke.
BACKGROUND
Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke.


METHODS
In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years.


RESULTS
The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke (1237 patients had had previous small-vessel or lacunar infarcts, 576 had had cryptogenic infarcts, and 259 had had infarcts designated as due to severe stenosis or occlusion of a large artery).


CONCLUSIONS
Over two years, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives.
Mohr
J P
JP
Neurological Institute, Columbia Presbyterian Medical Center, New York, NY 10032, USA. jpm10@columbia.edu
Thompson
J L
JL
Lazar
R M
RM
Levin
B
B
Sacco
R L
RL
Furie
K L
KL
Kistler
J P
JP
Albers
G W
GW
Pettigrew
L C
LC
Adams
H P
HP
Jackson
C M
CM
Pullicino
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D009026:Mortality; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D055502:Secondary Prevention; D020521:Stroke / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D001241:Aspirin