NEW YORK (Reuters Health) – Smoking does not affect outcomes after early clopidogrel use in patients with acute coronary syndrome (ACS), according to findings published in the November American Heart Journal.

“We could not find a significant interaction with smoking status,” Dr. Shaun G. Goodman and Dr. Matthew Sibbald from University of Toronto told Reuters Health in an email. “Even if one does exist (based on previous work), we believe clinicians should prescribe clopidogrel regardless of smoking status. In other words, this is an area that requires further study, but the data thus far should not result in a change in routine clinical practice.”

Dr. Goodman, Dr. Sibbald, and colleagues in the Global Registry of Acute Coronary Events (GRACE) study examined the association between clopidogrel use and in-hospital outcomes among 44,426 patients with ACS in relation to smoking status before hospitalization. Just over a quarter of the patients (12,149, 27%) were current smokers.

Based on findings in earlier studies (including CLARITY-TIMI 28 and CHARISMA), the investigators expected smokers treated with early clopidogrel to have a greater reduction in adverse cardiovascular events and a higher risk of bleeding compared to nonsmokers.

Overall, clopidogrel use was associated with a lower risk of in-hospital death or reinfarction adjusted for risk score and smoking status. Individually, there was a lower adjusted risk of in-hospital death but not reinfarction after clopidogrel treatment.

However, when patients were stratified by smoking status, that factor had no effect on in-hospital death or myocardial infarction, or 6-month death or myocardial infarction, among those treated with clopidogrel.

Clopidogrel use was independently associated with an increased risk of major bleeding among non-smokers but not among smokers, but after correcting for quintiles of propensity score, major bleeding was increased among all early clopidogrel users.

“The patients used in our analysis are quite different from those in previous papers,” Dr. Goodman and Dr. Sibbald said. “Our data comes from unselected patients in a large registry, in contrast to prior data from randomized trials. In our broader group of patients, we did not find a significant association.”

They added, “This suggests that clopidogrel efficacy is likely similar among smokers and non-smokers in a broad population of ACS patients; however, we also recognize the limitations of our approach since it is difficult to control for all variables that can impact ACS outcomes. Thus our work doesn’t mean the previous work is no longer relevant, but offers another perspective in a non-clinical trial population.”

The two researchers concluded, “We believe there are other databases that can explore this question, including post hoc analyses from clinical trial populations of newer antiplatelet agents vs. clopidogrel. As more antiplatelet agents become available, the question of whether the antiplatelet agent should be tailored to the patient is going to be increasingly important, and theoretically, this could apply to smoking status. However, we’ve learned from on treatment platelet reactivity and genetic studies that it isn’t always easy to pick out which patients will or will not ‘respond’ to clopidogrel.”

Reference:

Association between smoking, outcomes, and early clopidogrel use in patients with acute coronary syndrome: Insights from the Global Registry of Acute Coronary Events

Am Heart J 2010;160:855-861.