Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.
OBJECTIVE
The purpose of this study was to determine the possible benefit of dual antiplatelet therapy in patients with prior myocardial infarction (MI), ischemic stroke, or symptomatic peripheral arterial disease (PAD).


BACKGROUND
Dual antiplatelet therapy with clopidogrel plus aspirin has been validated in the settings of acute coronary syndromes and coronary stenting. The value of this combination was recently evaluated in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial, where no statistically significant benefit was found in the overall broad population of stable patients studied.


METHODS
We identified the subgroup in the CHARISMA trial who were enrolled with documented prior MI, ischemic stroke, or symptomatic PAD.


RESULTS
A total of 9,478 patients met the inclusion criteria for this analysis. The median duration of follow-up was 27.6 months. The rate of cardiovascular death, MI, or stroke was significantly lower in the clopidogrel plus aspirin arm than in the placebo plus aspirin arm: 7.3% versus 8.8% (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01). Additionally, hospitalizations for ischemia were significantly decreased, 11.4% versus 13.2% (HR 0.86, 95% CI 0.76 to 0.96, p = 0.008). There was no significant difference in the rate of severe bleeding: 1.7% versus 1.5% (HR 1.12, 95% CI 0.81 to 1.53, p = 0.50); moderate bleeding was significantly increased: 2.0% versus 1.3% (HR 1.60, 95% CI 1.16 to 2.20, p = 0.004).


CONCLUSIONS
In this analysis of the CHARISMA trial, the large number of patients with documented prior MI, ischemic stroke, or symptomatic PAD appeared to derive significant benefit from dual antiplatelet therapy with clopidogrel plus aspirin. Such patients may benefit from intensification of antithrombotic therapy beyond aspirin alone, a concept that future trials will need to validate. (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA]; http://clinicaltrials.gov/ct/show/NCT00050817?order=1; NCT00050817).
Bhatt
Deepak L
DL
Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. bhattd@ccf.org
Flather
Marcus D
MD
Hacke
Werner
W
Berger
Peter B
PB
Black
Henry R
HR
Boden
William E
WE
Cacoub
Patrice
P
Cohen
Eric A
EA
Creager
Mark A
MA
Easton
J Donald
JD
Hamm
Christian W
CW
Hankey
Graeme J
GJ
Johnston
S Claiborne
SC
Mak
Koon-Hou
KH
Mas
Jean-Louis
JL
Montalescot
Gilles
G
Pearson
Thomas A
TA
Steg
P Gabriel
PG
Steinhubl
Steven R
SR
Weber
Michael A
MA
Fabry-Ribaudo
Liz
L
Hu
Tingfei
T
Topol
Eric J
EJ
Fox
Keith A A
KA
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D020521:Stroke / Q000188:drug therapy*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin