Smoker’s Paradox Still Seen in STEMI Patients in Primary PCI Era

Among patients undergoing primary PCI for STEMI, both current and former smokers are less likely to die in the hospital than their smoke-free counterparts, a new study shows.

The relationship was strongest in current smokers, but even those who had quit carried a lower risk of in-hospital mortality compared with those with no history of smoking, lead author Tanush Gupta, MD (New York Medical College, Valhalla, NY), and colleagues report online in the Journal of the American Heart Association.

“Our findings should not be interpreted as an endorsement of cigarette smoking,” Gupta told TCTMD in an email. “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.”

Thus, he said, “aggressive efforts to encourage smoking cessation to reduce the overall cardiovascular burden should remain the utmost priority.”

The smoker’s paradox has been observed in the STEMI population since before thrombolytic therapy was developed, but the few studies looking at the topic during the era of primary PCI have provided conflicting results, raising questions about whether the phenomenon still exists in a contemporary patient population.

To explore the issue, the investigators tapped the National Inpatient Sample database to examine results of 985,174 patients who underwent primary PCI but not thrombolysis between 2003 and 2012; among them, 44.6% were current or former smokers. Those with a reported history of smoking were about 8 years younger than other patients, on average.

In-hospital mortality was less frequent among smokers, and the difference remained after multivariate adjustment (2.0% vs 5.9%; adjusted OR 0.60; 95% CI 0.58-0.62). The relationship weakened in older age groups and became nonsignificant in patients 90 years and older.

Smoking also was associated with a shorter length of stay (mean 3.5 vs 4.5 days; P < 0.001) and lower rates of postprocedure hemorrhage (4.2% vs 6.1%; adjusted OR 0.81; 95% CI 0.80-0.83) and in-hospital cardiac arrest (1.3% vs 2.1%; adjusted OR 0.78; 95% CI 0.76-0.81).

To assess whether the paradoxical relationship between smoking and in-hospital mortality could be due to disparities between smokers and nonsmokers in general—and not specifically in patients with STEMI—the researchers looked at the relationship in conjunction with two noncardiovascular conditions: hip fractures and severe sepsis. Smokers in both populations had a lower risk of in-hospital mortality compared with those who had never smoked.

“Since there is no cogent biological hypothesis to explain the existence of the smoker's paradox either in patients with hip fractures or severe sepsis, confounding likely accounts at least partly for the smoker’s paradox,” Gupta said.

Of note, the link was stronger in patients with hip fractures, for whom the age difference between smokers (who were younger) and those who had quit was double that seen in the septic population (8 vs 4 years). “These findings,” the authors write, “suggest that the lower risk-adjusted in-hospital mortality in hospitalized smokers was driven in part by residual confounding due to inadequate adjustment for the biological effects of age.”

Nevertheless, the fact that the paradoxical relationship was stronger in patients with STEMI compared with either those with hip fracture or those with sepsis suggests that there are pathophysiological mechanisms, too, Gupta noted. Prior studies, he pointed out, have shown that the potency of antiplatelet and antithrombotic drugs is greater in smokers.

But, he and his colleagues conclude, “Whether a true biochemical basis exists for the smoker’s paradox remains inconclusive.”

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