Is Smokers’ Paradox in STEMI Patients Treated With PCI Real?

MedicalResearch.com Interview with:

Tanush Gupta, MD Chief Resident & Instructor of Medicine Department of Medicine New York Medical College & Westchester Medical Center Valhalla, NY

Dr. Tanush Gupta

Tanush Gupta, MD
Chief Resident & Instructor of Medicine
Department of Medicine
New York Medical College & Westchester Medical Center
Valhalla, NY 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Gupta: Cigarette smoking is the leading preventable cause of premature death in the United States (U.S.). Approximately one-third of all coronary artery disease related deaths in the U.S. annually can be attributed to cigarette smoking. However, studies from the pre-thrombolytic and thrombolytic eras have shown that mortality in smokers with ST-segment elevation myocardial infarction (STEMI) may be lower than in nonsmokers, a phenomenon called the “smoker’s paradox.”

The majority of STEMI patients in contemporary practice are treated with primary percutaneous coronary intervention (pPCI). Data on the association of smoking with outcomes in STEMI patients undergoing pPCI are limited and also conflicting as to whether the smoker’s paradox exists in this population. Hence, the purpose of our study was to examine the association of smoking status with in-hospital outcomes in a nationwide cohort of STEMI patients undergoing pPCI, included in the U.S. National Inpatient Sample, over a 10-year time period from 2003 to 2012. Our primary outcome of interest was in-hospital mortality and secondary outcomes were post-procedure hemorrhage, in-hospital cardiac arrest, and average length of stay.

Of 985,174 STEMI patients who underwent pPCI in the U.S. over this time period, 438,954 (44.6%) were smokers. Smokers were on an average 8 years younger than nonsmokers and had lower prevalence of most cardiovascular comorbidities. Smoking status was associated with lower risk-adjusted in-hospital mortality (2.0% vs. 5.9%, adjusted OR 0.60, p<0.001), lower incidence of post-procedure hemorrhage (4.2% vs. 6.1%, adjusted OR 0.81, p<0.001) and in-hospital cardiac arrest (1.3% vs. 2.1%, adjusted OR 0.78, p<0.001), and shorter average length of stay (3.5 days vs. 4.5 days, p<0.001). To assess whether younger age of smokers was influencing the association with in-hospital mortality, we also performed an age-stratified analyses in different age groups. The smoker’s paradox largely persisted in age-stratified analyses suggesting that younger age of smokers was not the sole explanation for this paradox.

We performed additional assessment for confounding to explore whether the paradoxically lower risk-adjusted in-hospital mortality in smokers with STEMI was driven by differences in baseline demographics and comorbidities between hospitalized smokers and nonsmokers in general. To test for such confounding, we examined the association of smoking with in-hospital mortality in 2 conditions in which this association has not been previously studied – hip fractures and severe sepsis – using similar statistical regression models. In both these study populations, smokers were on average younger than nonsmokers and had lower risk-adjusted in-hospital mortality, but, the paradoxical association in both these conditions was weaker in magnitude than in STEMI patients. Since there is no cogent biological hypothesis to explain the lower mortality in smokers with sepsis or hip fractures, it is likely that the smoker’s paradox in STEMI is also at least partly driven by residual confounding due to inadequate adjustment for the biological effects of age. However, as this paradox was stronger in STEMI patients than in patients with hip fractures or severe sepsis, we believe that additional true biological differences between smokers and nonsmokers with STEMI also contribute to the paradoxically lower in-hospital mortality.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Gupta: The phenomenon of “smoker’s paradox” in STEMI has been described for over 25 years. Most of the supporting data come from the time period before the widespread use of pPCI for STEMI. The data on the validity of this paradox among STEMI patients treated with pPCI are very limited. Our study assesses the association of smoking status with in-hospital outcomes in a large and nationally representative cohort of STEMI patients admitted over a 10-year period to U.S. hospitals. Our findings support the existence of the smoker’s paradox in STEMI patients treated with pPCI.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Gupta: Our study findings show that the smoker’s paradox in STEMI patients undergoing pPCI is at least partly driven by continued unmeasured confounding. However, additional pathophysiological differences, such as greater responsiveness to antiplatelet therapies such as clopidogrel and prasugrel in smokers than in nonsmokers, also possibly contribute to this paradox. Future studies are needed to conclusively demonstrate whether such biological differences between smokers versus nonsmokers also contribute to the smoker’s paradox in STEMI.

MedicalResearch.com: Is there anything else you would like to add?

Dr. Gupta: This apparent “smoker’s paradox” should not be viewed as an endorsement of cigarette smoking. There is substantial evidence for the harmful nature of smoking and these modest differences in in-hospital outcomes noted in our study would likely be offset by the long-term mortality attributable to cigarette smoking. Hence, aggressive efforts to encourage smoking cessation to reduce the overall cardiovascular burden should remain the utmost priority.

Citation: Gupta T, Kolte D, Khera S, Harikrishnan P, Mujib M, Aronow WS, Jain D, Ahmed A, Cooper HA, Frishman WH, Bhatt DL, Fonarow GC, Panza JA. Smoker’s Paradox in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. J Am Heart Association 2016;5:e003370.

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