Smoking, clopidogrel, and mortality in patients with established cardiovascular disease

Berger, Jeffrey S., Bhatt, Deepak L., Steinhubl, Steven R., Shao, Mingyuan, Steg, P. Gabriel, Montalescot, Gilles, Hacke, Werner, Fox, Keith A., Lincoff, A. Michael, Topol, Eric J., Berger, Peter B., CHARISMA Investigators and Walker, Philip J. (2009) Smoking, clopidogrel, and mortality in patients with established cardiovascular disease. Circulation, 120 23: 2337-2344. doi:10.1161/CIRCULATIONAHA.109.866533

Author Berger, Jeffrey S.
Bhatt, Deepak L.
Steinhubl, Steven R.
Shao, Mingyuan
Steg, P. Gabriel
Montalescot, Gilles
Hacke, Werner
Fox, Keith A.
Lincoff, A. Michael
Topol, Eric J.
Berger, Peter B.
CHARISMA Investigators
Walker, Philip J.
Title Smoking, clopidogrel, and mortality in patients with established cardiovascular disease
Journal name Circulation   Check publisher's open access policy
ISSN 0009-7322
Publication date 2009-12-08
Sub-type Article (original research)
DOI 10.1161/CIRCULATIONAHA.109.866533
Volume 120
Issue 23
Start page 2337
End page 2344
Total pages 8
Place of publication Baltimore, MD, U.S.A.
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Background— Smoking increases platelet aggregability and the degree of platelet inhibition by clopidogrel on ex vivo platelet function tests. Whether smoking status affects the relationship between clopidogrel and clinical outcomes is unknown.

Methods and Results— We evaluated the relationship between smoking status (current smoker, former smoker, or never-smoker) and treatment with clopidogrel on the risk of all-cause, cardiovascular, and cancer mortality among the 12 152 participants from the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial who had established cardiovascular disease. Current smoking was associated with an increase in all-cause (adjusted hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.85 to 3.60), cardiovascular (HR 2.26, 95% CI 1.48 to 3.45), and cancer (HR 3.56, 95% CI 1.96 to 6.46) mortality compared with never smoking. The impact of clopidogrel on mortality differed by smoking status (P for interaction=0.018 for current smokers). Among current smokers, clopidogrel was associated with a reduction in all-cause mortality (HR 0.68, 95% CI 0.49 to 0.94); clopidogrel did not reduce all-cause mortality among former smokers (HR 0.95, 95% CI 0.75 to 1.19) or never-smokers (HR 1.14, 95% CI 0.83 to 1.58). A similar pattern was noted for cardiovascular mortality. As expected, no relationship was observed between clopidogrel and cancer mortality by smoking status. The risk of bleeding appeared to differ according to smoking status; randomized clopidogrel was associated with a significantly increased risk of severe or moderate bleeding (HR 1.62, P=0.04) among current smokers but a smaller and nonsignificant increase among never-smokers (HR 1.31, P=0.15).

Conclusions— Clopidogrel therapy may be more effective in current smokers, but it may also confer a greater bleeding risk than in nonsmokers. Further studies are needed to investigate this possibility.
Keyword Smoking
Cardiovascular disease
Acute Myocardial-Infarction
Atherothrombotic events
Thrombolytic therapy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Philip J. Walker is a member of the CHARISMA Investigators

Document type: Journal Article
Sub-type: Article (original research)
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