Interaction between cigarette smoking and clinical benefit of clopidogrel.
OBJECTIVE
The aim of this study was to examine the interaction between cigarette smoking and the clinical efficacy of clopidogrel in ST-segment elevation myocardial infarction (STEMI).


BACKGROUND
Cigarette smoking induces cytochrome P450 (CYP)1A2, which converts clopidogrel into its active metabolite, and prior studies suggest greater inhibition of platelet aggregation by clopidogrel in smokers of > or =10 cigarettes/day.


METHODS
The effect of clopidogrel compared with placebo on angiographic and clinical outcomes was examined in 3,429 STEMI patients in the CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28) randomized trial stratified by smoking intensity as follows: not current smokers (n = 1,732), and smokers of 1 to 9 (n = 206), 10 to 19 (n = 354), 20 to 29 (n = 715), and > or =30 cigarettes/day (n = 422). Logistic regression was used to adjust for other baseline characteristics and interaction terms to test for effect modification.


RESULTS
Although clopidogrel reduced the rate of the primary end point of a closed infarct-related artery or death/myocardial infarction before angiography in the CLARITY-TIMI 28 trial, the benefit was especially marked among those who smoked > or =10 cigarettes/day (adjusted odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.37 to 0.66; p < 0.0001) compared with those who did not (adjusted OR: 0.72, 95% CI: 0.57 to 0.91; p = 0.006; p(interaction) = 0.04). Similarly, clopidogrel was significantly more effective at reducing the rate of cardiovascular death, myocardial infarction, or urgent revascularization through 30 days among those who smoked > or =10 cigarettes/day (adjusted OR: 0.54, 95% CI: 0.38 to 0.76; p = 0.0004) compared with those who did not (adjusted OR: 0.98; 95% CI: 0.75 to 1.28; p = 0.87; p(interaction) = 0.006).


CONCLUSIONS
Cigarette smoking seems to positively modify the beneficial effect of clopidogrel on angiographic and clinical outcomes. This study demonstrates that common clinical factors that influence the metabolism of clopidogrel might impact its clinical effectiveness.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Nihar R
NR
Desai
Jessica L
JL
Mega
Songtao
S
Jiang
Christopher P
CP
Cannon
Marc S
MS
Sabatine
D000368:Aged; D000077144:Clopidogrel; D004562:Electrocardiography; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012907:Smoking; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine