Letters Section Editor: Jody W. Zylke, MD, Senior Editor.
Author Affiliations: Sinai Center for Thrombosis Research, Baltimore, Maryland (Dr Gurbel; firstname.lastname@example.org); University of Pittsburgh, School of Pharmacy, Pittsburgh, Pennsylvania (Dr Nolin); and Sinai Center for Thrombosis Research, Baltimore, Maryland (Dr Tantry).
In Reply: In our Viewpoint, we highlighted a potential limitation of clopidogrel therapy: an absence of documented clinical efficacy in nonsmokers rather than a benefit in smokers. We would like to further clarify the 2 issues regarding our Viewpoint that were raised.
First, Dr Sibbing and colleagues assert that smokers “are more prone to develop thrombotic events compared with nonsmokers.” The available data do not validate this assertion. Although a higher event rate in smokers treated with aspirin therapy alone was observed in the Clopidogrel for the Reduction of Events During Observation (CREDO) and Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trials, the same was not observed in the Clopidogrel versus Aspirin In Patients at Risk of Ischaemic Events (CAPRIE), Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE), and Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) trials. This inconsistent outcome argues against an intrinsic prothrombotic state in smokers to explain the smokers' paradox. These 5 trials demonstrated that clopidogrel efficacy was negligible or absent among nonsmokers and smokers did not consistently experience greater thrombotic event occurrence.
Gurbel PA, Nolin TD, Tantry US. Influence of Smoking on Treatment With Clopidogrel—Reply. JAMA. 2012;308(13):1322-1324. doi:10.1001/2012.jama.11193