The Smoker's Paradox Revisited: A Patient-Level Pooled Analysis of 18 Randomized Controlled Trials

JACC Cardiovasc Interv. 2019 Oct 14;12(19):1941-1950. doi: 10.1016/j.jcin.2019.06.034. Epub 2019 Sep 11.

Abstract

Objectives: This study examined the smoker's paradox using patient-level data from 18 prospective, randomized trials of patients undergoing percutaneous coronary intervention (PCI) with stent implantation.

Background: Studies on the effects of smoking and outcomes among patients undergoing PCI have reported conflicting results.

Methods: Data from the RAVEL, E-SIRIUS, SIRIUS, C-SIRIUS, TAXUS IV and V, ENDEAVOR II to IV, SPIRIT II to IV, HORIZONS-AMI, COMPARE I and II, PLATINUM, and TWENTE I and II randomized trials were pooled. Patients were stratified by smoking status at time of enrollment. The 1- and 5-year ischemic outcomes were compared.

Results: Among 24,354 patients with available data on smoking status, 6,722 (27.6%) were current smokers. Smokers were younger and less likely to have diabetes mellitus; hypertension; hyperlipidemia; or prior myocardial infarction (MI), PCI, or coronary artery bypass grafting. Angiographically, smokers had longer lesions, more complex lesions, and more occlusions, but were less likely to have moderate or severe calcification or tortuosity. At 5 years, smokers had significantly higher rates of MI (7.8% vs. 5.6%; p < 0.0001) and definite or probable stent thrombosis (3.5% vs. 1.8%; p < 0.0001); however, there were no differences in the rates of death, cardiac death, target lesion revascularization, or composite endpoints (cardiac death, target vessel MI, or ischemic target lesion revascularization). After multivariable adjustment for potential confounders, smoking was a strong independent predictor of death (hazard ratio [HR]: 1.86; 95% confidence interval [CI]: 1.63 to 2.12; p < 0.0001), cardiac death (HR: 1.68; 95% CI: 1.38 to 2.05; p < 0.0001), MI (HR: 1.38; 95% CI: 1.20 to 1.58; p < 0.0001), stent thrombosis (HR: 1.60; 95% CI: 1.28 to 1.99; p < 0.0001), and target lesion failure (HR: 1.17; 95% CI: 1.05 to 1.30; p = 0.005).

Conclusions: The present large, patient-level, pooled analysis with 5-year follow-up clearly demonstrates smoking to be an important predictor of adverse outcomes after PCI.

Keywords: coronary artery disease; coronary artery disease outcomes; smokers; smoker’s paradox.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Coronary Artery Bypass* / adverse effects
  • Coronary Artery Bypass* / mortality
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy*
  • Coronary Thrombosis / mortality
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / mortality
  • Myocardial Infarction / therapy*
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / instrumentation
  • Percutaneous Coronary Intervention* / mortality
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Smokers*
  • Smoking / adverse effects*
  • Smoking / mortality
  • Stents
  • Time Factors
  • Treatment Outcome