Mad Honey Disease.

A 46-year-old woman presented to the emergency room with acute onset of nausea, vomiting and prostration. She appeared ill and was poorly responsive to verbal stimuli. Physical examination showed a systolic blood pressure of 60 mmHg and a pulse of 40 bpm. ECG was notable for slight ST-elevations in the inferior leads. Right ventricular myocardial infarction with cardiogenic shock and bradycardia was suspected. Supportive therapy with catecholamines was initiated and an emergency coronary angiography was arranged. However, laboratory results showed normal troponin levels and a subsequent echocardiogram showed the absence of abnormal wall motion. Thorough history taking with the spouse revealed that the patient had consumed Turkish honey approximately 1 h before the symptoms began. The patient made a full recovery within 24 h with only supportive therapy. In retrospect, the clinical presentation was highly indicative of poisoning with grayanotoxins from the rhododendron plant, which contaminate some types of honey in the Black Sea area. A pollen analysis confirmed the presence of rhododendron in a honey sample. Historically this poisoning is referred to as mad honey disease. The ST-elevations in the ECG were a sign of early repolarization, a non-pathological finding. LEARNING POINTS: ST-elevation in the inferior leads of an ECG in the context of hypotension and bradycardia does not always indicate right myocardial infarction.In the proper context, intoxication with grayanotoxins should be included in the differential diagnosis of hypotension and bradycardia.Study of diseases occurring in the past in a particular region offers the physician the chance to make a diagnosis otherwise missed.

[Treatment and Secondary Prevention of Venous Thromboembolism - Change in Oral Anticoagulation]. / Therapie und Sekundärprävention der venösen Thromboembolie ­ Orale Antikoagulation im Wandel.

With the recent approval of the fourth direct non vitamin K dependent oral anticoagulant (NOAC) edoxaban the range of available NOACs for the treatment of venous thromboembolism (VTE) has expanded. Shortly thereafter, two updated guidelines for the prevention and treatment of VTE have been published. In these NOACs are listed as equal anticoagulants to low-molecular weight heparin (LMWH), or fondaparinux (FDX), and VKA for the initial or maintenance treatment of VTE. All NOACs are approved for the maintenance therapy after VTE and two NOACs (rivaroxaban and apixaban) for the initial treatment in addition in an increased dose.NOACs differ in their pharmacodynamic and pharmacokinetic properties. In patients with renal insufficiency the dose of all NOACs should be reduced similarly to NMH/FDX. In contrast to VKAs, bridging with NOACs in case of surgical interventions is generally dispensable. Similar to NMHs or FPX renal function and individual bleeding risk dependent dose intermission is generally sufficient. Conventional coagulation parameters like aPTT and INR are not suitable for the monitoring of NOACs. Only in seldom cases, laboratory monitoring with use of adjusted anti-Xa testing or diluted thrombin time (dabigatran) may be helpful.

Late Consequences of Acute Coronary Syndromes: Global Registry of Acute Coronary Events (GRACE) Follow-up.

PURPOSE: Short-term outcomes have been well characterized in acute coronary syndromes; however, longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore, we describe the longer-term outcomes, procedures, and medication use in Global Registry of Acute Coronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performance of the discharge GRACE risk score in predicting 2-year mortality. METHODS: Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome were enrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronary syndrome diagnosis in 57 sites. RESULTS: From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge, 14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery, and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), beta-blocker (80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heart failure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE risk score was highly predictive of all-cause mortality at 2 years (c-statistic 0.80). CONCLUSION: In this large multinational cohort of acute coronary syndrome patients, there were important later adverse consequences, including frequent morbidity and mortality. These findings were seen in the context of additional coronary procedures and despite continued use of evidence-based therapies in a high proportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors for predicting longer-term mortality was maintained.

Late Consequences of Acute Coronary Syndromes: Global Registry of Acute Coronary Events (GRACE)Follow-up

PURPOSE: Short-term outcomes have been well characterized in acute coronary syndromes; however,longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation myocardialinfarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore,we describe the longer-term outcomes, procedures, and medication use in Global Registry of AcuteCoronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performanceof the discharge GRACE risk score in predicting 2-year mortality.METHODS: Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome wereenrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronarysyndrome diagnosis in 57 sites.RESULTS: From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge,14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery,and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), betablocker(80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heartfailure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE riskscore was highly predictive of all-cause mortality at 2 years (c-statistic 0.80).CONCLUSION: In this large multinational cohort of acute coronary syndrome patients, there were importantlater adverse consequences, including frequent morbidity and mortality. These findings were seen in thecontext of additional coronary procedures and despite continued use of evidence-based therapies in a highproportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors forpredicting longer-term mortality was maintained.

Management and outcomes of patients presenting with STEMI by use of chronic oral anticoagulation: results from the GRACE registry.

AIMS: To describe the characteristics, treatment, and mortality in patients with ST-elevation myocardial infarction (STEMI) by use of chronic oral anticoagulant (OAC) therapy. METHODS: Using data from the Global Registry of Acute Coronary Syndromes (GRACE), patient characteristics, treatment, and reperfusion strategies of STEMI patients on chronic OAC are described, and relevant variables compared with patients not on chronic OAC. Six-month post-discharge mortality rates were evaluated by Cox proportional hazard models. RESULTS: Of 19,094 patients with STEMI, 574 (3.0%) were on chronic OAC at admission. Compared with OAC non-users, OAC users were older (mean age 73 vs. 65 years), more likely to be female (37 vs. 29%), were more likely to have a history of atrial fibrillation, prosthetic heart valve, venous thromboembolism, or stroke/transient ischaemic attack, had a higher mean GRACE risk score (166 vs. 145), were less likely to be Killip class I (68 vs. 82%), and were less likely to undergo catheterization/percutaneous coronary intervention (52 vs. 66%, respectively). Of the patients who underwent catheterization, fewer OAC users had the procedure done within 24 h of admission (56.5 vs. 64.5% of OAC non-users). In propensity-matched analyses (n=606), rates of in-hospital major bleeding and in-hospital and 6-month post-discharge mortality were similar for OAC users and OAC non-users (2.7 and 3.7%, p=0.64; 15 and 13%, p=0.56; 15 and 12%, p=0.47, respectively), rates of in-hospital recurrent myocardial infarction (8.6 and 2.0%, p<0.001) and atrial fibrillation (32 and 22%, p=0.004) were higher in OAC patients, and rates of 6-month stroke were lower (0.6 and 4.3%, p=0.038). Patients in both groups who underwent catheterization had lower mortality than those who did not undergo catheterization. CONCLUSIONS: This is the largest study to describe the characteristics and treatment of STEMI patients on chronic OAC. The findings suggest that patients on chronic OAC are less likely to receive guideline-indicated management, but have similar adjusted rates of in-hospital and 6-month mortality.

Independent predictors of bleeding complications in patients undergoing PCI with concomitant treatment with bivalirudin in clinical practice results from the ImproveR registry.

BACKGROUND: Bleeding complications are associated with an adverse outcome after a percutaneous coronary intervention (PCI) is performed. Traditional risk factors for bleeding complications are age, gender, underweight, hypertension, and renal impairment. The aim of our study was to identify the independent predictors of bleeding complications in patients undergoing a PCI with concomitant treatment with bivalirudin. METHODS: Between January 2005 and June 2006, a total of 3799 patients, undergoing a planned or urgent PCI with concomitant bivalirudin treatment, were prospectively enrolled in the ImproveR registry. One hundred two centers out of 12 European countries participated in the ImproveR registry. In this analysis, we report the incidence of bleeding complications in subgroups to be at a high risk for developing bleeding complications. A multivariate logistic regression model was performed to identify the independent predictors of bleeding complications. RESULTS: Major bleeding complications occurred in 1.7% of the patients. The highest incidence of major bleeding complications was observed in the subgroup with a sheath size ≥7F (4.3%), heparin use after the PCI (3.5%), and additional use of GP IIb/IIIa inhibitors (3.3%). The multivariate regression analysis revealed female gender [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.4-3.8], heparin after the PCI (OR, 3.1; 95% CI, 1.9-5.1), and sheath size ≥7F (OR, 3.1; 95% CI, 1.8-5.4) as the independent predictors of bleeding. CONCLUSIONS: The rate of occurrence of bleeding complications in patients undergoing a PCI with concomitant use of bivalirudin is low in clinical practice. Female gender and procedural factors, such as sheath size and heparin after PCI, were associated with an increase in bleeding complications, whereas other traditional risk factors associated with bleeding, such as age, diabetes mellitus, and renal impairment, had no impact.

Antiplatelet agents for the treatment and prevention of atherothrombosis.

The clinical pharmacology of antiplatelet drugs has been reviewed previously by the European Society of Cardiology (ESC) Task force and by the 8th American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. Moreover, information on the efficacy and safety of antiplatelet drugs in the treatment and prevention of atherothrombosis is provided by collaborative meta-analyses of 287 secondary prevention trials and 6 primary prevention trials. The present document intends to provide practicing physicians with an updated instrument to guide their choice of the most suitable antiplatelet strategy for the individual patient at risk, or with different clinical manifestations, of atherothrombosis.

Bleeding in acute coronary syndromes and percutaneous coronary interventions: position paper by the Working Group on Thrombosis of the European Society of Cardiology.

Bleeding has recently emerged as an important outcome in the management of acute coronary syndromes (ACS), which is relatively frequent compared with ischaemic outcomes and has important implications in terms of prognosis, outcomes, and costs. In particular, there is evidence that patients experiencing major bleeding in the acute phase are at higher risk for death in the following months, although the causal nature of this relation is still debated. This position paper aims to summarize current knowledge regarding the epidemiology of bleeding in ACS and percutaneous coronary intervention, including measurement and definitions of bleeding, with emphasis on the recent consensus Bleeding Academic Research Consortium (BARC) definitions. It also provides an European perspective on management strategies to minimize the rate, extent, and consequences of bleeding. Finally, the research implications of bleeding (measuring and reporting bleeding in trials, the importance of bleeding as an outcome measure, and bleeding as a subject for future research) are also discussed.

Prognostic utility of quantifying evolutionary ST-segment depression on early follow-up electrocardiogram in patients with non-ST-segment elevation acute coronary syndromes.

AIMS: Although ST-segment depression (STD) on the admission electrocardiogram (ECG) confers adverse prognosis in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), the implications of STD on follow-up ECG remain uncertain. We determined the prognostic significance of STD on follow-up ECG performed within 12-24 h of admission and whether its quantitative evaluation can further refine risk stratification. METHODS AND RESULTS: The admission and follow-up ECGs of 3877 patients in the SYNERGY trial were analysed for the presence (>or=1 mm) and extent (maximum magnitude on any single lead) of STD. Of the 1110 patients presenting with STD on admission, 534 (48.1%) with persistent STD at follow-up had higher mortality at 30 days (7.1 vs. 3.6%, P = 0.01) and 6 months (10.7 vs. 5.2%, P = 0.001) than those with normalized STD. Among 2767 patients without STD on admission, 174 (6.3%) developed new STD on follow-up ECG and experienced increased mortality compared with those without such interval change (30 days: 4.0 vs. 1.7%, P = 0.035; 6 months: 8.0 vs. 3.3%, P = 0.001). After adjustment for established clinical prognosticators and the extent of STD on admission, every 1 mm increment of STD on the follow-up ECG independently predicted a graded increase in 30-day mortality [hazards ratio (HR) = 1.60, 95% confidence interval (CI) = 1.29-1.98, P < 0.0001], and death/myocardial infarction at 30 days (HR = 1.19, 95% CI = 1.03-1.36, P = 0.017) and 6 months (HR = 1.17, 95% CI = 1.03-1.32, P = 0.016). CONCLUSION: The magnitude of STD on a routine 12-24 h follow-up ECG provides incremental prognostic information beyond established clinical prognosticators and the extent of STD on admission. Incorporating a follow-up ECG and its quantitative evaluation for STD may further refine risk stratification of patients with NSTE-ACS.

Association of non-steroidal anti-inflammatory drugs with outcomes in patients with ST-segment elevation myocardial infarction treated with fibrinolytic therapy: an ExTRACT-TIMI 25 analysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) may be prothrombotic, may worsen hypertension or congestive heart failure and obstruct access to the binding site of aspirin to cyclooxygenase-1 and thereby interfere with aspirin's mechanism of action in reducing death and recurrent myocardial infarction (MI). We hypothesized that treatment with NSAIDs prior to an index MI would be associated with an increase in the risk of death, heart failure and recurrent MI among patients with ST-segment elevation MI (STEMI) treated with fibrinolytic therapy. METHODS: In ExTRACT-TIMI 25, patients with STEMI were treated with aspirin and fibrinolytic therapy and randomized to either enoxaparin or unfractionated heparin. We included patients who had received NSAIDs within 7 days of enrollment and evaluated the incidence of MI, the composite of death and MI and the composite of death, MI, severe heart failure and shock through 30 days. RESULTS: Of 20,479 patients enrolled, 572 (2.8%) received an NSAID within 7 days of enrollment. NSAID treatment prior to entry was associated with a higher incidence of 30-day death or nonfatal recurrent MI (15.9% vs. 10.8%, univariate P < 0.001). In multivariable models adjusting for randomization group and differences in baseline characteristics, NSAID use was associated with higher odds of MI (adjusted odds ratio [OR(adj)] 1.44, 95% confidence interval [CI] 1.01-2.07, P = 0.047), the composite of death and MI (OR(adj) 1.29, 95% CI 1.00-1.66, P = 0.051), and the composite of death, MI, severe heart failure and shock (OR(adj) 1.29, 95% CI 1.02-1.65, P = 0.037). CONCLUSIONS: Among STEMI patients treated with a fibrinolytic agent and aspirin, use of NSAIDs in the week preceding the incident event was associated with a higher incidence of MI, the composite of death and MI as well as the composite of death, MI, severe heart failure and shock at 30 days.

Time to coronary angiography and outcomes among patients with high-risk non ST-segment elevation acute coronary syndromes: results from the SYNERGY trial.

BACKGROUND: Optimal timing for an early invasive strategy in patients with non-ST-segment-elevation acute coronary syndrome remains unclear. We evaluated the relationship between time from hospital admission to coronary angiography and outcomes in high-risk patients with non-ST-segment-elevation acute coronary syndrome who underwent angiography within 48 hours of admission. METHODS AND RESULTS: Data from 10 027 patients enrolled in the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial were analyzed. Patients were grouped by 6-hour intervals of time from hospital admission to coronary angiography. Primary outcomes were 30-day death or myocardial infarction, in-hospital Thrombolysis In Myocardial Infarction (TIMI) and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) major bleeding, and blood transfusion. Adjusted estimates of event rates were obtained by use of a multivariable methodology that included possible confounders through baseline and accounted for propensity of time to angiography. The landmark method was used to calculate odds ratios and 95% confidence intervals of outcomes for each time period adjusted for baseline and postbaseline clinical events. Overall, 9216 patients (92%) underwent angiography, 6352 (63%) within 48 hours. Unadjusted and adjusted rates of death/myocardial infarction increased with increasing time to angiography. The adjusted odds ratio for death/myocardial infarction in patients receiving angiography in <6 hours was 0.56 (95% confidence interval 0.41 to 0.74), whereas after 30 hours, there was no significant benefit compared with further delayed angiography. Major bleeding and transfusion did not vary significantly across time-to-angiography intervals. CONCLUSIONS: A decrease in the time to coronary angiography was associated with fewer ischemic outcomes and no increase in bleeding. Randomized clinical trials are needed to provide definitive evidence on optimal timing of coronary angiography but are difficult to design and conduct. Ongoing trials should instead clarify whether delaying angiography to administer aggressive upstream antithrombotic therapies is effective in the current setting of non-ST-segment-elevation acute coronary syndrome management.

Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial.

OBJECTIVES: We sought to evaluate whether enoxaparin (ENOX) is superior to unfractionated heparin (UFH) as adjunctive therapy for patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy and subsequently undergo percutaneous coronary intervention (PCI) by analyzing data from the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial. BACKGROUND: Limited data are available on the use of ENOX compared with UFH as adjunctive therapy in STEMI patients treated with fibrinolytic therapy and subsequent PCI. METHODS: A total of 20,479 STEMI patients who received fibrinolytic therapy were randomized to a strategy of ENOX throughout index hospitalization or UFH for at least 48 h, with blinded study drug to continue if PCI was performed. The primary end point of death or recurrent MI through 30 days was compared for ENOX versus UFH among the patients who underwent subsequent PCI (n = 4,676). RESULTS: After initial fibrinolysis, fewer patients underwent PCI through 30 days in the ENOX versus the UFH group (22.8% vs. 24.2%; p = 0.027). Among patients who underwent PCI by 30 days, the primary end point occurred in 10.7% of ENOX and 13.8% of UFH patients (0.77 relative risk; p < 0.001). There were no differences in major bleeding for ENOX versus UFH (1.4% vs. 1.6%; p = NS). Results were similar when PCI was carried out in patients receiving blinded study drug during PCI (n = 2,178). CONCLUSION: Among patients treated with fibrinolytic therapy for STEMI who underwent subsequent PCI, ENOX administration was associated with a reduced risk of death or recurrent MI without difference in the risk of major bleeding. The strategy of ENOX support for fibrinolytic therapy followed by PCI is superior to UFH and provides a seamless transition from the medical management to the interventional management phase of STEMI without the need for introducing a second anticoagulant in the cardiac catheterization laboratory.

Combining warfarin and antiplatelet therapy after coronary stenting in the Global Registry of Acute Coronary Events: is it safe and effective to use just one antiplatelet agent?

AIMS: To identify factors associated with the use of single or dual antiplatelet therapy in patients prescribed warfarin following coronary stenting and to investigate whether single (aspirin or thienopyridine) vs. dual antiplatelet therapy plus warfarin leads to an excess of adverse outcomes. METHODS AND RESULTS: We analysed data from 800 patients with an acute coronary syndrome who underwent coronary stenting (130 patients received a drug-eluting stent) and were discharged on warfarin and either dual (n = 580) or single (n = 220) antiplatelet therapy. The use of single antiplatelet therapy was more common in Europe than in the USA (34 vs. 17%, P < 0.001). There was no difference in major bleeding in hospital or in 6-month mortality or myocardial infarction. In the single antiplatelet group, the use of either aspirin or thienopyridine (clopidogrel or ticlopidine) in combination with warfarin resulted in similar outcomes. CONCLUSION: Use of single vs. dual antiplatelet therapy and warfarin following stenting is common. In this observational study, there was no difference in mortality or myocardial infarction at 6 months; however, larger trials are needed to assert any firm recommendations.

[Clinical assessment of potential fields of application of recombinant factor VIIa in internal and pediatric diseases. Recommendations of an expert group]. / Klinische Bewertung potentieller Einsatzbereiche von rekombinantem Faktor VIIa bei internistischen und pädiatrischen Erkrankungen: Empfehlungen einer Expertengruppe.

Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for treatment of life-threatening bleeding episodes after failure of the respective standard therapy. An interdisciplinary group of experts summarizes the state of knowledge of the use of rFVIIa in gastroenterology and hepatology, thrombocytopenia and -pathia, coagulation factor deficiencies, von Willebrand's disease, periinterventional bleeding without specific bleeding diathesis, drug-induced bleeding, disseminated intravascular coagulation, and neonatology. The most commonly used dose is 90 microg/kg body weight rFVIIa as bolus, if necessary followed by additional injections at intervals of 2-3 h. In factor VII deficiency lower dosages of 15-30 microg/kg body weight of rFVIIa are given every 4-6 h, whereas higher doses of 150-200 microg/kg body weight are used in neonates.

Bleeding complications in patients with acute coronary syndrome undergoing early invasive management can be reduced with radial access, smaller sheath sizes, and timely sheath removal.

OBJECTIVES: Our objective was to analyze the impact of arterial access site, sheath size, timing of sheath removal, and use of access site closure devices on high-risk patients with acute coronary syndromes (ACS). BACKGROUND: In the SYNERGY trial, 9,978 patients with ACS were randomly assigned to receive enoxaparin or unfractionated heparin. METHODS: This analysis includes 9,404 patients for whom sheath access information was obtained for the first PCI procedure or diagnostic catheterization. Comparisons of baseline, angiographic, and procedural characteristics were carried out according to access site and sheath size. RESULTS: Overall, 9,404 (94%) patients underwent angiography at a median of 21 hr (25th and 75th percentiles: 5, 42) and 4,687 (50%) underwent PCI at a median of 23 hr (6,49) of enrollment. The access site was femoral for 94.9% of cases, radial for 4.4%, and brachial for 0.7%. Radial access was associated with fewer transfusions than femoral access (0.9% vs. 4.8%, P=0.007). For femoral access, the rates of noncoronary artery bypass grafting (CABG)-related TIMI major bleeding by sheath size was 1.5% for 4 or 5 French (Fr), 1.6% for 6 Fr, 3.3% for 7 Fr, and 3.8% for >or=8 Fr (P<0.0001). After adjustment for baseline characteristics, femoral access site, larger sheath size, and delayed sheath removal were independent predictors of need for transfusion. CONCLUSIONS: Smaller sheaths, radial access, and timely sheath removal may mitigate the bleeding risk associated with potent antithrombotic/platelet therapy and early catheterization.

Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events.

AIMS: To determine whether low-molecular-weight heparin (LMWH)+glycoprotein (GP) IIb/IIIa inhibitors provide greater benefit than unfractionated heparin (UFH)+GP IIb/IIIa inhibitors, irrespective of renal status. METHODS AND RESULTS: Patients in the Global Registry of Acute Coronary Events (GRACE) were divided into three groups according to creatinine clearance (CrCl): normal renal function (CrCl >60 mL/min), moderate renal dysfunction (30

Cigarette smoking and acute coronary syndromes: a multinational observational study.

PURPOSE: To determine the impact of cigarette smoking on the presentation, treatment, and in-hospital outcomes of patients admitted with the full spectrum of acute coronary syndromes. METHODS: GRACE is a multinational observational registry involving 94 hospitals in 14 countries. This analysis is based on 19,325 patients aged at least 18 years admitted for acute coronary syndromes as a presumptive diagnosis with at least one of the following: electrocardiographic changes consistent with acute coronary syndromes, serial increases in serum biochemical markers of cardiac necrosis, and/or documentation of coronary artery disease. The main outcomes measured were mode of presentation, treatment and in-hospital death in the ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina groups to assess the impact of smoking status. RESULTS: Smokers were more frequently diagnosed with ST-segment elevation myocardial infarction (46.0%) than former smokers (27.4%) and non-smokers (30.2%) (P<0.001). Smokers were mostly men, were younger and more aggressively treated than former smokers and non-smokers across the three acute coronary syndrome groups. Unadjusted in-hospital mortality rates were lower in smokers compared with former smokers and non-smokers in the study population (3.3%, 4.5%, and 6.9%, respectively, P<0.001), and in the ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction groups. However, by multivariate logistic analysis, the adjusted in-hospital mortality rate was similar regardless of smoking status. CONCLUSIONS: There is no survival advantage related to current or prior cigarette smoking in patients admitted with acute coronary syndromes, regardless of presentation. In this large multinational registry, the smokers' paradox does not exist.