Is there a time when it would be more harmful to encourage a patient to quit smoking? I had a patient who was a 60-year-old man with an extensive cardiovascular disease history, which included four stents, who most recently presented with an S-T elevation myocardial infarction (STEMI) to the psychiatric emergency room complaining of a panic attack. The patient was taken for percutaneous intervention (PCI) and was discharged from coronary care unit (CCU) to the inpatient psychiatric unit on the usual post myocardial infarction (MI) regimen, which he had been taking prior to the new cardiac event, of a beta blocker, ACE-inhibitor, statin, aspirin, and clopidogrel (Plavix®). The patient happens to have a history of smoking 5–10 cigarettes per day for the last 20 years. Other comorbidities include major depressive disorder, cervical spine stenosis, and alcoholism.
During his psychiatric hospital stay he reported atypical chest pain. Cardiology was consulted. A Holter monitor was ordered as was a Plavix resistance assay (VerifyNow P2Y12). Patients who take clopidogrel tend to have a variable response to the antiplatelet effect; it has been estimated that approximately 5%–30% of patients do not have adequate platelet response (incomplete blockade of the platelet membrane P2Y12) to clopidogrel (Muller et al., 2003; Serebruany et al., 2005). As I was investigating the clinical utility of the Plavix resistance assay P2Y12, I discovered the “smokers paradox” through a brief literature review limited to full text articles available online; this concept was surprising to me and most of my colleagues with whom I shared my findings.
The “smokers paradox” is a phrase given to the research findings that patients who smoke have more favorable outcomes after an acute myocardial infarction (AMI) compared to nonsmokers. One such study is the OPTIMAL trial in which 5447 high-risk patients after AMI who were taking losartan were followed; findings revealed that smokers in the trial had a 17% smaller risk of death as compared to non-smokers after adjusting for patient age (Jaatun, Sutradhar, & Dickstein, 2004).
The position held and supported by many clinical studies from the medical community teaches the parade of “horribles” associated with cigarette smoking (higher overall mortality, endothelial dysfunction, dyslipidemia, platelet dysfunction, insulin resistance). Cigarette smoking is known to induce the CYP450 and CYP1A2 systems. The CYP1A2 is the isoenzyme that converts clopidogrel into the active metabolite. The stimulation of CYP1A2 that is associated with smoking has been shown to enhance platelet inhibition (Deasi, Mega, Jiang, Cannon, & Sabatine, 2009). The study by Deasi et al. (2009) investigated the interaction between cigarette smoking and the clinical benefit of clopidogrel in STEMI patients (n = 3429) and concluded “cigarette smoking seems to positively modify the beneficial effect of clopidogrel on angiographic clinical outcomes” (p. 1273).
In another study designed to explore the relationship between smoking, clopidogrel, and cardiovascular mortality in patients with established cardiovascular disease, clopidogrel therapy was found to be more effective in people who smoke (Berger et al., 2009). In a study by Bliden et al. (2008) of 259 consecutive patients undergoing elective insertion of coronary stents (n = 120 were taking chronic clopidogrel; n = 139 were clopidogrel-naïve and preoperatively loaded with 600 mg), current smokers concurrently taking clopidogrel had increased platelet inhibition and decreased platelet aggregation. Similarly, a study by Price et al. (2008) in patients (n = 377) with stable coronary artery disease on maintenance antiplatelet therapy with clopidogrel reported a higher residual platelet reactivity based on the VerifyNow P2Y12 assay stratification, which has been shown to be predictive of cardiovascular events. Patients who were active smokers had lower residual platelet reactivity. Women, non-Caucasians, patients with diabetes, nitrates users, and proton pump inhibitor users who were taking clopidogrel all had significantly higher residual platelet reactivity measures on theVerifyNow P2Y12 assay.
Given these findings, I pose the following question: How insistent should a clinician be with encouraging smoking cessation particularly in the post-MI patient? Considering that in the area of illicit drug abuse much of the current practice is now aimed at harm reduction instead of total abstinence, why is harm reduction not an option for smoking? It appears to be that in smoking, abstinence is the only acceptable standard of care. Therefore, I pose the question again: Is there a time when it would be more harmful to encourage a patient to quit smoking? Healthcare providers should consider the evidence that cigarette smoking can in some cases be beneficial, and it is up to healthcare providers to investigate the literature before we insist on and support health policies that all patients quit smoking. Further questions for researchers to consider include the mechanism by which cigarette smoking enhances antiplatelet activity, as currently it does not appear that nicotine alone is the helpful agent.