How do smokers differ from nonsmokers in their response to thrombolysis? (the TIMI-4 trial)

Smokers with acute myocardial infarction appear to have a better outcome after thrombolysis than do nonsmokers. To identify factors that could contribute to this curious finding, we analyzed data from the Thrombolysis in Myocardial Infarction (TIMI-4) trial, in which 382 patients with acute myocardial infarction were randomized to tissue plasminogen activator, anistreplase, or both. Coronary angiography was performed 90 minutes and 18 to 36 hours after randomization, a myocardial perfusion scan was performed at 18 to 36 hours and before discharge, and a radionuclide ventriculogram was obtained before discharge. Angiographic and clinical outcome variables were determined in current smokers, ex-smokers, and nonsmokers, and regression analysis was used to correct for differences in baseline characteristics. The in-hospital mortality of current smokers was lower than that of ex-smokers and nonsmokers: 2.3% versus 5.2% versus 7.0%, respectively (p = 0.04 by paired comparison, current vs nonsmokers). Ninety minutes after randomization, the incidence of TIMI grade 3 flow was significantly higher in smokers than in ex-smokers and nonsmokers (55% vs 43% and 45%, p = 0.02); this difference was no longer observed at the second angiogram, nor did smokers differ from nonsmokers with respect to residual stenosis, thrombus grade, infarct size, ejection fraction, or recurrent ischemia. Because a strong inverse relation exists between TIMI grade 3 flow at 90 minutes and mortality, our findings suggest that the lower mortality of current smokers after thrombolytic therapy may be related to a higher incidence of early, complete reperfusion.