Smoking-Thrombolysis Paradox: Recanalization and Reperfusion Rates After Intravenous Tissue Plasminogen Activator in Smokers With Ischemic Stroke

A. Kufner, C. H. Nolte, I. Galinovic, P. Brunecker, G. M. Kufner, M. Endres, J. B. Fiebach, M. Ebinger
2013 Stroke  
S moking is a well-known risk factor for premature atherosclerosis, myocardial infarction and ischemic stroke. 1 However, some studies have shown that smokers with myocardial infarction have lower mortality rates after thrombolysis than nonsmokers. [2] [3] [4] [5] Some have questioned the accuracy of this so-called smoking-thrombolysis paradox and attributed the effect to the low clinical risk profiles of these patients. 6 Then again, imaging studies have shown improved myocardial perfusion
more » ... owing thrombolysis in smokers despite adjustment for age and other comorbidities, offering an alternative explanation for the smoking phenomenon. 3, 7 Improved tissue reperfusion in smokers may be explained by an enhanced causal mechanism. Tissue plasminogen activator (tPA) is a fibrinolytic factor released from the endothelium to prevent intravascular thrombus formation 8 ; smoking impairs endogenous tPA release and causes circulating fibrinogen levels to rise. 9,10 Studies have demonstrated that cigarette smoke exposure alters clot dynamics and thrombus composition, consequently causing blood to become hypercoagulable. 10,11 It has been suggested that the increased risk of ischemic heart disease associated with smoking is largely mediated by increased intra-arterial fibrin concentrations. 12 Although this may predispose smokers to early vessel occlusion, the fibrin-rich thrombus in smokers may be more susceptible to fibrinolytic treatment. 2 Thus, tPA may act more specifically in smokers, thereby counterbalancing the adverse effects of this pathophysiological risk factor. Background and Purpose-The so-called smoking-thrombolysis paradox of an improved outcome after thrombolysis was first described in smokers with myocardial infarction. We investigated whether reperfusion rates and clinical outcome differ between smokers and nonsmokers with ischemic stroke after intravenous tissue plasminogen activator. Methods-Consecutive acute ischemic stroke patients, who had magnetic resonance imaging before and 1 day after thrombolysis, were included for analysis. All of the patients received intravenous tissue plasminogen activator within 4.5 hours. Reperfusion was defined as a 75% reduction in perfusion deficit (mean transit time >6 s) after thrombolysis compared with baseline. Magnetic resonance angiography was used to evaluate arterial stenosis and occlusion. Functional outcome was assessed 3 months after stroke using the modified Rankin Score. Results -Of 148 patients, 21.6% were smokers (n=32). Smokers were younger (median, 61 years [SD, 9.4 years] versus 75 years [SD, 11.6 years]; P<0.001), less often women (28% versus 51%; P=0.03), had lower baseline glucose levels (median, 6.2 mmol/L [interquartile range, 5.7-6.8 mmol/L] versus 6.7 mmol/L [interquartile range, 6.1-8.2 mmol/L]; P<0.01) and higher baseline perfusion deficits (median, 53 mL [interquartile range, 13-141 mL] versus 17 mL [interquartile range, 2-66 mL]; P=0.04). In a backward stepwise regression analysis including age, sex, hypertension, glucose, perfusion deficit, and smoking, smoking had an odds ratio of 4 (95% confidence interval, 1-16; P=0.03) for reperfusion and 6 (95% confidence interval, 1-30; P=0.05) for recanalization (regression analysis for recanalization also included localization of arterial occlusion). Smokers had a better outcome (modified Rankin Score=0-2) than nonsmokers (77% versus 55%; P=0.05). Conclusions-Smoking is independently associated with recanalization and reperfusion, indicating that thrombolytic therapy acts more effectively in smokers; because of small numbers, these results should be considered preliminary. Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique Identifier: NCT00715533. (Stroke. 2013;44:407-413.)
doi:10.1161/strokeaha.112.662148 pmid:23287785 fatcat:a7tbz5frubfq7oca7vfd4xvenu