Worse prognosis for smokers after primary PCI in STEMI, pooled data shows

The “smoker’s paradox” of better outcomes for smokers after acute myocardial infarction (AMI) may be illusory, or even reversed, pooled trial data suggested.

Data from 2,564 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) showed that although smokers and nonsmokers had similar infarct size, microvascular obstruction (MVO), and left ventricular ejection fraction (LVEF), smokers had higher 1-year rates of reinfarction and composite death or heart failure (HF) hospitalization.

Crude 1-year rates of all-cause death were 1.0% for smokers versus 2.9% in non-smokers (P<0.001) and rates of death or HF hospitalization were 3.3% versus 5.1% (P=0.009), with similar rates of reinfarction, reported Gregg Stone, MD, of Icahn School of Medicine at Mount Sinai in New York City, and coauthors.

But after adjusting for age and other risk factors, smokers had a similar 1-year risk of death (adjusted HR 0.92, 95% CI 0.46-1.84) as non-smokers, and higher risks of death or HF hospitalization (adjusted HR 1.49, 95% CI 1.09-2.02) as well as reinfarction (adjusted HR1.97, 95% CI 1.17-3.33), they wrote in the Journal of the American College of Cardiology.

On average, smokers were 10 years younger than non-smokers and more likely to be men (80% versus 76%).

“Recent smoking was unrelated to infarct size or MVO but was associated with a worse prognosis after primary PCI in STEMI,” Stone and colleagues noted. “The smoker’s paradox may be explained by the younger age and fewer cardiovascular risk factors in smokers compared with nonsmokers.”

“Smoking is bad, and smokers have MIs 10 years earlier,” wrote Harvey White, DSC, of the University of Auckland in New Zealand, in an accompanying editorial. “The HR for the composite of death and heart failure was lower in smokers prior to adjustment but higher after adjustment. It is unusual for HRs to move in opposite directions with adjustment. As with all-cause mortality, age was the greatest factor explaining this flip-flop in HR.”

Although smoking is a clear risk factor for cardiovascular disease, including STEMI, some prior work has shown that recent smokers have a better prognosis after STEMI than nonsmokers. The concept has been challenged and modified: a recent study that included 5-year outcomes in a 24,354 patient sample with 6,722 current smokers found that smokers were younger and less likely to have vascular risk factors. Smokers also had longer, more complex lesions and more occlusions, but less calcification and tortuosity. Smokers had increased 5-year rates of MI and definite/probable stent thrombosis than non-smokers, and adjusted analysis showed smoking to be an independent predictor of death, cardiac death, AMI, stent thrombosis, and target lesion failure.

Other predictive measures in this setting include infarct size measured within a month of primary PCI, which independently predicts all-cause mortality and HF hospitalization within 1 year, and microvascular obstruction, which is associated with 1 year mortality and HF hospitalization.

Stone and colleagues explored the relationship between recent smoking, infarct size, and prognosis in STEMI with PCI through analysis of data from 10 randomized trials. All trials included STEMI patients treated with primary PCI and had infarct size measured with MRI or SPECT within a month of PCI.

The definition of recent smoking ranged from current smoking to smoking within 3 months prior to symptom onset. All included studies had 6 months or more of follow-up (median 349 days; interquartile range 185-370 days) and adjudication of new events. The primary clinical endpoints were all-cause death, hospitalization for HF, and the composite of all cause death or HF hospitalization.

Among 2,564 patients with STEMI, 1,093 (42.6%) were recent smokers. Smokers were 10 years younger on average than non-smokers (55 versus 65 years) and had fewer comorbidities, including hypertension (43% versus 57% for smokers and nonsmokers, respectively), hyperlipidemia (20% versus 26%), and diabetes (13% versus 20%). Infarct size was similar in smokers and nonsmokers.

Though baseline thrombolysis in myocardial infarction (TIMI) flow grades were similar for smokers and non-smokers, final TIMI flow grade 3 (better flow) was higher among smokers than nonsmokers (92% versus 89%, respectively).

“The improvement in epicardial TIMI flow grade 3 in smokers compared with nonsmokers surprisingly did not translate into improved microcirculatory perfusion, reduced infarct size, reduced MVO, or improved prognosis; this remains a paradox opposite to the previous smoker’s paradox,” the editorialist wrote.

Limitations include varying definitions of recent smoking in the included trials. Also, intramyocardial hemorrhage was not assessed, there was no information on smoking rates after MI, and mortality after reinfarction was not reported.

“The observed lower 1-year crude rates of adverse events among smokers compared with nonsmokers were explained predominantly by their younger age,” Stone and co-authors wrote. “After accounting for this factor and other baseline differences, smokers were at substantially higher risk for reinfarction and the composite of death or HF hospitalization.”

“This fact, compounded by the occurrence of STEMI 10 years earlier in smokers compared with nonsmokers, should lay to rest any residual belief that smoking is beneficial to atherosclerosis development, progression, or treatment,” they added.

  1. The “smoker’s paradox” of better outcomes for smokers after acute myocardial infarction may be explained by younger age and fewer cardiovascular risk factors in smokers compared with non-smokers, pooled trial data suggested.

  2. After adjusting for age and other factors, smokers had higher risk of death or heart failure hospitalization and a higher rate of reinfarction than non-smokers 1 year after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI).

Paul Smyth, MD, Contributing Writer, BreakingMED™

Stone has served as a consultant to Miracor, TherOx, and Abiomed.

White reported relationships with Sanofi, Regeneron Pharmaceuticals, Omthera Pharmaceuticals, Pfizer, American Regent, Eisai, DalCor Pharma UK, CSL Behring, Esperion Therapeutics, Genentech, and AstraZeneca.

Cat ID: 358

Topic ID: 74,358,254,791,730,358,143,192,489,925


Bjorn Redfors B, et al “Effect of smoking on outcomes of primary PCI in patients with STEMI” Amer Coll Cardiol 2020; 75(15): 1743-1754.

White H “Deconstructing the paradox of smoking and improved short-term cardiovascular outcomes after myocardial infarction” J Amer Coll Cardiol 2020; 75(15): 1755-1757.