Effect of clopidogrel on the rate and functional severity of stroke among high vascular risk patients: a prespecified substudy of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial.
OBJECTIVE
Disabling stroke is costly and considered by some patients a fate worse than death. We aimed to determine whether clopidogrel reduces the rate and functional severity of stroke among high vascular risk patients, including patients with previous transient ischemic attack or ischemic stroke, who were enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial.


METHODS
We randomly assigned 15,603 high vascular risk patients to receive clopidogrel (75 mg daily) or placebo in addition to background acetylsalicylic acid and followed them for a median of 28 months. The main outcome of this prespecified substudy was the functional severity of stroke outcome events as measured by the modified Rankin Scale (mRS) score at 3 months after the stroke outcome.


RESULTS
During follow-up, 436 (2.8%) patients had a definite adjudicated stroke and a follow-up assessment of the mRS at 3 months poststroke, of whom 202 had been randomly assigned clopidogrel and 234 placebo (relative risk reduction 14%, 95% CI: -4% to 29%, P=0.12). There was no significant difference between the mean mRS scores at 3 months after stroke among patients assigned clopidogrel compared with placebo (mean mRS 3.6 [SD 2.4] clopidogrel versus 3.3 [SD 2.1] placebo; P=0.15). There was also no significant difference between the various categories of the mRS score at 3 months after stroke among patients assigned to clopidogrel compared with placebo. Among 4320 patients with a qualifying diagnosis of transient ischemic attack or ischemic stroke, 233 (5.4%) experienced a stroke during follow-up, of whom 103 were randomly assigned clopidogrel and 130 placebo (relative risk reduction 20%, 95% CI: -3% to 38%). There was no significant difference between the mean mRS scores at 3 months after stroke among patients with a qualifying transient ischemic attack or ischemic stroke who were assigned clopidogrel compared with placebo (3.4 [SD 2.1] clopidogrel versus 3.3 [SD 1.9] placebo; P=0.48).


CONCLUSIONS
The addition of clopidogrel to acetylsalicylic acid did not significantly alter the rate and functional severity of stroke outcome events among high vascular risk patients enrolled in the CHARISMA trial.
Hankey
Graeme J
GJ
Neurology Department, Royal Perth Hospital, Perth, Australia. gjhankey@cyllene.uwa.edu.au
Hacke
Werner
W
Easton
J Donald
JD
Johnston
S Claiborne
SC
Mas
Jean-Louis
JL
Brennan
Danielle M
DM
Bhatt
Deepak L
DL
Fox
Keith A A
KA
Topol
Eric J
EJ
D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015994:Incidence; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D040242:Risk Reduction Behavior; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin