March 20, 2006|
Bedrood and Asher Kimchi M.D.
Cleveland, Ohio -
Platelets have been
shown to play a central role in atherothrombosis.
Low dose aspirin can reduce ischemic outcomes by
inhibiting the cyclooxygenase pathway. Clopidogrel
inhibits platelet aggregation by inhibiting the
binding of ADP to the platelet receptor and thereby
inhibiting the consequent activation of the
glycoprotein GPIIb/IIIa complex. A study by Dr.
Deepak Bhatt et al from the Cleveland Clinic in Ohio
was published in the March 14, 2006 issue of The New
England Journal of Medicine indicating clopidogrel
plus aspirin was not significantly more effective
than aspirin alone in reducing the rate of
myocardial infarction, stroke or death from
The study 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.
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).
Overall, the study concluded that dual therapy with
clopidogrel and aspirin does not significantly reduce the rate
of myocardial infarction, stroke and cardiovascular death and
thus should not be recommended as a preventative therapy for
such disease processes.
The study was presented at an American College of Cardiology
meeting in Atlanta.
Co-authors: Deepak L. Bhatt, M.D., Keith A.A. Fox, M.B., Ch.B.,
Werner Hacke, M.D., Peter B. Berger, M.D., Henry R. Black, M.D.,
William E. Boden, M.D., Patrice Cacoub, M.D., Eric A. Cohen,
M.D., Mark A. Creager, M.D., J. Donald Easton, M.D., Marcus D.
Flather, M.D., Steven M. Haffner, M.D., Christian W. Hamm, M.D.,
Graeme J. Hankey, M.D., S. Claiborne Johnston, M.D., Koon-Hou
Mak, M.D., Jean-Louis Mas, M.D., Gilles Montalescot, M.D.,
Ph.D., Thomas A. Pearson, M.D., P. Gabriel Steg, M.D., Steven R.
Steinhubl, M.D., Michael A. Weber, M.D., Danielle M. Brennan,
M.S., Liz Fabry-Ribaudo, M.S.N., R.N., Joan Booth, R.N., Eric J.
Topol, M.D., for the CHARISMA Investigators