NEW YORK (Reuters Health) – Smoking does not affect platelet reactivity or clinical effectiveness in patients who have received clopidogrel, according to a report in the August 11th online American Heart Journal.
Smoking enhances the activity of CYP1A2, which is important for the metabolic activation of clopidogrel. Smoking might, therefore, increase the activity of clopidogrel.
“When we started with our analysis, we expected to see an interaction and planned to compare the effect of smoking with the effect of well known factors impacting of the antiplatelet response to clopidogrel,” Dr. Willibald Hochholzer from the TIMI Study Group, Boston, Massachusetts told Reuters Health by email. “However, we didn’t find any association of smoking with the effect of clopidogrel across all analyzed studies. Since we’ve analyzed almost all possible settings of clopidogrel treatment we conclude that the potential interaction of smoking with bioactivation of clopidogrel has no meaningful clinical effect.”
Dr. Hochholzer and colleagues investigated the impact of smoking on platelet function and on clinical outcome in 5 cohorts of patients undergoing percutaneous coronary intervention (PCI) while receiving aspirin and clopidogrel or prasugrel.
In the 4 studies examining platelet aggregation, there were no significant differences regarding on-clopidogrel platelet aggregation for active smokers versus nonsmokers after loading and on maintenance therapy. In none of the cohorts was smoking status associated with on-clopidogrel platelet reactivity.
In the study comparing clopidogrel with prasugrel (whose biotransformation does not appear to be influenced by CYP1A2), there was no significant difference in clinical efficacy (the combined primary end point of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) between the treatments for patients who smoked and those who did not.
“The central finding of our analysis is not only the negative result for smoking but the identification of three simple clinical factors interacting with the antiplatelet response to clopidogrel throughout all analyzed cohorts: age, diabetes, and body mass index,” Dr. Hochholzer explained. “This might help clinicians to identify patients at risk for a low response to clopidogrel.”
“Most of the coauthors of this manuscript and other research groups have identified and confirmed several clinical and genetic factors interacting with the effect of clopidogrel,” Dr. Hochholzer said. “The next step will be to investigate if similar factors also impact on the effect of newer antiplatelet agents such as ticagrelor and prasugrel in large clinical cohorts.”
“Regarding smoking subjects,” Dr. Hochholzer concluded, “I would not recommend any change in antiplatelet treatment.”
Reference:
Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy
Am Heart J 2011;0:1-9.e5
