The smoker’s paradox after successful fibrinolysis: reduced risk of reocclusion but no improved long-term cardiac outcome

Abstract

Background In smokers treated with fibrinolysis for ST-elevation myocardial infarction (STEMI) a paradoxical beneficial short-term outcome has been reported. This was attributed to favorable clinical and angiographic baseline variables and a better response to fibrinolysis. During follow-up infarct artery reocclusion is an important prognosticator. We studied the effects of smoking on reocclusion and long-term cardiac outcome after successful fibrinolysis. Methods In the Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis trials (APRICOT-1 and -2) 499 STEMI patients with an open infarct artery \48 h after fibrinolysis received randomized antithrombotic treatment until 3-month follow-up angiography. Five-year clinical follow-up was complete. Results Current smokers (317 patients, 64%) had favorable clinical (age 54 vs. 60 years, P \ 0.01) and angiographic (single vessel disease 61% vs. 49%, P = 0.02) baseline characteristics. Reocclusion rates were 21% (67/317) in smokers versus 32% (59/182) in nonsmokers (P \ 0.01). Five-year infarct-free cardiac survival did not differ: 82% vs. 85%. Reocclusion (HR 2.41, 95%CI 1.05-5.56, P = 0.04) independently predicted cardiac mortality. Smoking was independently associated with a reduced risk of reocclusion (OR 0.58, 95%CI 0.37-0.91, P = 0.02), but not with improved 5-year cardiac outcome (HR 1.34, 95%CI 0.79-2.25, P = ns). Conclusions After successful fibrinolysis, smoking is independently associated with a more than 40% reduced risk of reocclusion, which is an independent predictor of adverse outcome. However, even with more favorable baseline characteristics smokers did not have improved 5-year cardiac outcome in this low-risk population.

“Smoker’s Paradox” in Patients Treated for Severe Injuries: Lower Risk of Mortality After Trauma Observed in Current Smokers

“…Our study demonstrates that trauma patients experience a "smoker's paradox" similar to that of cardiovascular patients. 1,2,5,6,23,44 We found that there was an independent association between smoking status and mortality and complication outcomes in severely injured patients, with smoking greatly reducing the risk of death even after adjusting for potential confounders such as age. Several potential mechanisms may explain the protective effect of smoking following trauma and future studies investigating therapeutic applications of these findings should be conducted.…”

Absence of Smoker’s Paradox in Middle Eastern Patients with Acute Coronary Syndrome

“…The term "smoker's paradox" was coined in the thrombolysis era when the use of fibrinolytic agents was the main strategy for STEMI reperfusion, and the high thrombogenicity state in smokers might have predicted a more favorable response to fibrinolysis [28]. However, this response was not confirmed by all thrombolysis trials, such as the GUSTO-1 trial which did not find any difference in the prevalence of thrombi or residual stenosis between smokers and non-smoker receiving thrombolysis [29]. In the contemporary era of primary PCI the studies are less supportive of the presence of this paradox when correction for differences in baseline variables was considered [30,31].…”

Can divergent plasmin–antiplasmin–carbon monoxide interactions in young, healthy tobacco smokers explain the ‘smokerʼs paradox’?

“…myocardial infarction, stroke, peripheral vascular disease) has had smoking identified as a risk factor [1][2][3][4] for the acute ischemic event, there are a number of investigations that demonstrate a protective effect of smoking. Specifically in the setting of acute myocardial infarction (AMI), decreases in early/late mortality, reocclusion after thrombolysis, and restenosis rate after percutaneous intervention are lower in patients that smoke and continue to smoke [5][6][7][8][9][10]. This counterintuitive phenomenon is commonly referred to as the 'smoker's paradox', with smoking patients in general presenting 10 years earlier and with more severe infarction than their nonsmoking counterparts [5][6][7][8][9].…”

“…Specifically in the setting of acute myocardial infarction (AMI), decreases in early/late mortality, reocclusion after thrombolysis, and restenosis rate after percutaneous intervention are lower in patients that smoke and continue to smoke [5][6][7][8][9][10]. This counterintuitive phenomenon is commonly referred to as the 'smoker's paradox', with smoking patients in general presenting 10 years earlier and with more severe infarction than their nonsmoking counterparts [5][6][7][8][9]. However, in an investigation involving young (approximately 40 years old), age-matched cohorts of smokers and nonsmokers, the paradox was still present [10].…”

“…Further, 45% of these smokers had kinetically detectable carboxyhemefibrinogen (COHF), and 20% had COHF with hypercoagulability defined as clot strength greater than the 95% confidence interval (CI) value of nonsmokers [29]. This robust, carbon monoxidemediated augmentation of coagulation may be why initial infarction in smokers is earlier in onset [5][6][7][8][9] and can be more extensive [9,10] than nonsmokers [9]. However, both acute smoking and carbon monoxide exposure via carbon monoxide-releasing molecules (CORMs) result in a thinner fibrin polymer matrix [17,30] and a resistance to either thrombolysis [16] or simultaneous fibrinolysis [27,28] mediated by tPA.…”