Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.
BACKGROUND
Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events.


METHODS
We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes.


RESULTS
The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046).


CONCLUSIONS
In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.).
Cleveland Clinic, Cleveland, USA.
Deepak L
DL
Bhatt
Keith A A
KA
Fox
Werner
W
Hacke
Peter B
PB
Berger
Henry R
HR
Black
William E
WE
Boden
Patrice
P
Cacoub
Eric A
EA
Cohen
Mark A
MA
Creager
J Donald
JD
Easton
Marcus D
MD
Flather
Steven M
SM
Haffner
Christian W
CW
Hamm
Graeme J
GJ
Hankey
S Claiborne
SC
Johnston
Koon-Hou
KH
Mak
Jean-Louis
JL
Mas
Gilles
G
Montalescot
Thomas A
TA
Pearson
P Gabriel
PG
Steg
Steven R
SR
Steinhubl
Michael A
MA
Weber
Danielle M
DM
Brennan
Liz
L
Fabry-Ribaudo
Joan
J
Booth
Eric J
EJ
Topol
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D000077144:Clopidogrel; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D013927:Thrombosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin