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Objectives: This study was designed to determine the impact of bivalirudin on 1-year outcomes in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Background: The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial demonstrated that in moderate- and high-risk ACS patients undergoing PCI, bivalirudin alone compared to unfractionated heparin (UFH) or enoxaparin plus a glycoprotein (GP) IIb/IIIa inhibitor resulted in less major bleeding and similar ischemic outcomes at 30 days. The impact of bivalirudin on 1-year outcomes in ACS patients undergoing PCI is unknown. Methods: In the ACUITY trial, 13,819 patients were enrolled, and 7,789 (56.4%) patients had PCI. Composite ischemia (death, myocardial infarction, or unplanned revascularization) and mortality at 1 year were assessed. Results: Among patients undergoing PCI, 2,561, 2,609, and 2,619 were randomized to UFH or enoxaparin plus a GP IIb/IIIa inhibitor, bivalirudin plus a GP IIb/IIIa inhibitor, and bivalirudin monotherapy, respectively. At 1 year, there were no differences in composite ischemia (17.8% vs. 19.4% vs. 19.2%, p = NS) or mortality (3.2% vs. 3.3% vs. 3.1%, p = NS) among the 3 groups, respectively. Conclusions: Bivalirudin compared with UFH or enoxaparin plus a GP IIb/IIIa inhibitor results in similar rates of composite ischemia and mortality at 1 year in moderate- and high-risk ACS patients undergoing PCI. [Copyright &y& Elsevier]

: ObjectivesWe sought to examine contemporary utilization patterns and clinical outcomes in patients with acute myocardial infarction (AMI) requiring intra-aortic balloon pump (IABP) counterpulsation.: BackgroundDespite increasing experience with and broadened indications for intra-aortic counterpulsation, the current indications, associated complications, and clinical outcomes of IABP use in AMI are unknown.: MethodsBetween June 1996 and August 2001, data were prospectively collected from 22,663 consecutive patients treated with aortic counterpulsation at 250 medical centers worldwide; 5,495 of these patients had AMI.: ResultsPlacement of an IABP in AMI patients was most frequently indicated for cardiogenic shock (27.3%), hemodynamic support during catheterization and/or angioplasty (27.2%) or prior to high-risk surgery (11.2%), mechanical complications of AMI (11.7%), and refractory post-myocardial infarction unstable angina (10.0%). Balloon insertions were successful in 97.7% of patients. Diagnostic catheterization was performed in 96% of patients, and 83% underwent coronary revascularization before hospital discharge. The in-hospital mortality rate was 20.0% (38.7% in patients with shock) and varied markedly by indication and use of revascularization procedures. Major IABP complications occurred in only 2.7% of patients, despite median use for three days, and early IABP discontinuation was required in only 2.1% of patients.: ConclusionsWith contemporary advances in device technology, insertion technique, and operator experience, IABP counterpulsation may be successfully employed for a wide variety of conditions in the AMI setting, providing significant hemodynamic support with rare major complications in a high-risk patient population. [Copyright &y& Elsevier]

Patients undergoing early surgery after coronary stent implantation are at increased risk for mortality from ischemic and hemorrhagic complications. The optimal antiplatelet strategy in patients who cannot discontinue dual antiplatelet therapy (DAPT) before surgery is unclear. Current guidelines, based on surgical and clinical characteristics, provide risk stratification for bridging therapy with intravenous antiplatelet agents, but management is guided primarily by expert opinion. This review summarizes perioperative risk factors to consider before discontinuing DAPT and reviews the data for intravenous bridging therapies. Published reports have included bridging options such as small molecule glycoprotein IIb/IIIa inhibitors (eptifibatide or tirofiban) and cangrelor, an intravenous P2Y12 inhibitor. However, optimal management of these complex patients remains unclear in the absence of randomized controlled data, without which an argument can be made both for and against the use of perioperative intravenous bridging therapy after discontinuing oral P2Y12 inhibitors. Multidisciplinary risk assessment remains a critical component of perioperative care. [ABSTRACT FROM AUTHOR]

Background: The long-term prognostic impact of post-discharge bleeding in the unique population of patients with acute coronary syndrome (ACS) treated without percutaneous coronary intervention (PCI) remains unexplored.Objectives: The aim of this study was to assess the association between post-discharge bleeding and subsequent mortality after ACS according to index strategy (PCI or no PCI) and to contrast with the association between post-discharge myocardial infarction (MI) and subsequent mortality.Methods: In a harmonized dataset of 4 multicenter randomized trials (APPRAISE-2 [Apixaban for Prevention of Acute Ischemic Events-2], PLATO [Study of Platelet Inhibition and Patient Outcomes], TRACER [Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome], and TRILOGY ACS [Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes]), the association between post-discharge noncoronary artery bypass graft-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate, severe, or life-threatening bleeding (landmark 7 days post-ACS) and subsequent all-cause mortality was evaluated in a time-updated Cox proportional hazards analysis. Interaction with index treatment strategy was assessed. Results were contrasted with risk for mortality following post-discharge MI.Results: Among 45,011 participants, 1,133 experienced post-discharge bleeding events (2.6 per 100 patient-years), and 2,149 died during follow-up. The risk for mortality was significantly higher <30 days (adjusted hazard ratio: 15.7; 95% confidence interval: 12.3 to 20.0) and 30 days to 12 months (adjusted hazard ratio: 2.7; 95% confidence interval: 2.1 to 3.4) after bleeding, and this association was consistent in participants treated with or without PCI for their index ACS (p for interaction = 0.240). The time-related association between post-discharge bleeding and mortality was similar to the association between MI and subsequent mortality in participants treated with and without PCI (p for interaction = 0.696).Conclusions: Post-discharge bleeding after ACS is associated with a similar increase in subsequent all-cause mortality in participants treated with or without PCI and has an equivalent prognostic impact as post-discharge MI. [ABSTRACT FROM AUTHOR]

Background: Smoking is a well-established risk factor for ST-segment elevation myocardial infarction (STEMI); however, once STEMI occurs, smoking has been associated with favorable short-term outcomes, an observation termed the "smoker's paradox." It has been postulated that smoking might exert protective effects that could reduce infarct size, a strong independent predictor of worse outcomes after STEMI.Objectives: The purpose of this study was to determine the relationship among smoking, infarct size, microvascular obstruction (MVO), and adverse outcomes after STEMI.Methods: Individual patient-data were pooled from 10 randomized trials of patients with STEMI undergoing primary percutaneous coronary intervention. Infarct size was assessed at median 4 days by either cardiac magnetic resonance imaging or technetium-99m sestamibi single-photon emission computed tomography. Multivariable analysis was used to assess the relationship between smoking, infarct size, and the 1-year rates of death or heart failure (HF) hospitalization and reinfarction.Results: Among 2,564 patients with STEMI, 1,093 (42.6%) were recent smokers. Smokers were 10 years younger and had fewer comorbidities. Infarct size was similar in smokers and nonsmokers (adjusted difference: 0.0%; 95% confidence interval [CI]: -3.3% to 3.3%; p = 0.99). Nor was the extent of MVO different between smokers and nonsmokers. Smokers had lower crude 1-year rates of all-cause death (1.0% vs. 2.9%; p < 0.001) and death or HF hospitalization (3.3% vs. 5.1%; p = 0.009) with similar rates of reinfarction. After adjustment for age and other risk factors, smokers had a similar 1-year risk of death (adjusted hazard ratio [adjHR]: 0.92; 95% CI: 0.46 to 1.84) and higher risks of death or HF hospitalization (adjHR: 1.49; 95% CI: 1.09 to 2.02) as well as reinfarction (adjHR: 1.97; 95% CI: 1.17 to 3.33).Conclusions: In the present large-scale individual patient-data pooled analysis, recent smoking was unrelated to infarct size or MVO, but was associated with a worse prognosis after primary PCI in STEMI. The smoker's paradox may be explained by the younger age and fewer cardiovascular risk factors in smokers compared with nonsmokers. [ABSTRACT FROM AUTHOR]

Background: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial found clinical benefit of low-dose rivaroxaban plus aspirin, but at the expense of increased bleeding risk in patients with stable vascular disease.Objectives: This study evaluated the balance of ischemic and bleeding risks according to the presence of ≥1 enrichment criteria in "COMPASS-eligible" patients.Methods: Key COMPASS selection criteria were applied to identify a COMPASS-eligible population (n = 16,875) from the REACH (REduction of Atherothrombosis for Continued Health) Registry of stable atherothrombotic patients. Ischemic outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Bleeding outcome was serious bleeding (hemorrhagic stroke, hospitalization for bleeding, transfusion).Results: Patients were categorized according to the enrichment criteria: age >65 years (81.5%), diabetes (41.0%), moderate renal failure (40.2%), peripheral artery disease (33.7%), current smoker (13.8%), heart failure (13.3%), ischemic stroke (11.1%), and asymptomatic carotid stenosis (8.7%). Each criterion was associated with a consistent increase in ischemic and bleeding events, but no individual subgroup derived a more favorable trade-off. Patients with multiple criteria had a dramatic increase in ischemic risk (7.0% [95% confidence interval (CI): 5.6% to 8.7%], 12.5% [95% CI: 11.1% to 14.1%], 16.6% [95% CI: 14.7% to 18.6%], and 21.8% [95% CI: 19.9% to 23.9%] with 1, 2, 3, and ≥4 enrichment criteria, respectively), but a more modest absolute increase in bleeding risk (1.5% [95% CI: 0.9% to 2.1%], 1.8% [95% CI: 1.3% to 2.2%], 2.0% [95% CI: 1.5% to 2.6%], 3.2% [95% CI: 2.6% to 3.9%]).Conclusions: In a population of stable vascular patients at high risk of atherothrombotic events, the subset with multiple enrichment criteria had a greater absolute increase in ischemic than in bleeding risk and may be good candidates for low-dose rivaroxaban in addition to aspirin. [ABSTRACT FROM AUTHOR]

Background: Chronic angina is more common in patients with diabetes mellitus (DM) with poor glucose control. Ranolazine both treats chronic angina and improves glucose control.Objectives: This study sought to examine ranolazine's antianginal effect in relation to glucose control.Methods: The authors performed a secondary analysis of the RIVER-PCI (Ranolazine in Patients with Incomplete Revascularization after Percutaneous Coronary Intervention) trial, a clinical trial in which 2,604 patients with chronic angina and incomplete revascularization following percutaneous coronary intervention were randomized to ranolazine versus placebo. Mixed-effects models were used to compare the effects of ranolazine versus placebo on glycosylated hemoglobin (HbA1c) at 6- and 12-month follow-up. Interaction between baseline HbA1c and ranolazine's effect on Seattle Angina Questionnaire angina frequency at 6 and 12 months was tested.Results: Overall, 961 patients (36.9%) had DM at baseline. Compared with placebo, ranolazine significantly decreased HbA1c by 0.42 ± 0.08% (adjusted mean difference ± SE) and 0.44 ± 0.08% from baseline to 6 and 12 months, respectively, in DM patients, and by 0.19 ± 0.02% and 0.20 ± 0.02% at 6 and 12 months, respectively, in non-DM patients. Compared with placebo, ranolazine significantly reduced Seattle Angina Questionnaire angina frequency at 6 months among DM patients but not at 12 months. The reductions in angina frequency were numerically greater among patients with baseline HbA1c ≥7.5% than those with HbA1c <7.5% (interaction p = 0.07).Conclusions: In patients with DM and chronic angina with incomplete revascularization after percutaneous coronary intervention, ranolazine's effect on glucose control and angina at 6 months was proportionate to baseline HbA1c, but the effect on angina dissipated by 12 months. [ABSTRACT FROM AUTHOR]

Background: Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain.Objectives: The study investigated the efficacy and safety of the potent P2Y12 inhibitors in patients with coronary artery disease.Methods: A collaborative sex-specific meta-analysis was conducted of phase III or IV randomized trials of potent P2Y12 inhibitors, including prasugrel, ticagrelor, and intravenous cangrelor. Seven trials were included that enrolled a total of 24,494 women and 63,346 men. Major adverse cardiovascular events (MACE) were defined as the primary endpoint for each trial.Results: Potent P2Y12 inhibitors significantly reduced the risk of MACE by 14% in women (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.78 to 0.94) and by 15% in men (HR: 0.85; 95% CI: 0.80 to 0.90; p interaction = 0.93). Treatment reduced the risk of myocardial infarction by 13% in women (HR: 0.87; 95% CI: 0.78 to 0.96) and 16% in men (HR: 0.84; 95% CI: 0.77 to 0.91; p interaction = 0.65), and the risk of stent thrombosis by 51% in women (HR: 0.49; 95% CI: 0.37 to 0.65) and 41% in men (HR: 0.59; 95% CI: 0.42 to 0.84; p interaction = 0.85). Directional consistency was seen for cardiovascular death in women (HR: 0.87; 95% CI: 0.76 to 1.01) and men (HR: 0.85; 95% CI: 0.77 to 0.95; p interaction = 0.86). The potent P2Y12 inhibitors increased major bleeding in women (HR: 1.28; 95% CI: 0.87 to 1.88) and men (HR: 1.52; 95% CI: 1.12 to 2.07; p interaction = 0.62).Conclusions: In randomized trials, the efficacy and safety of the potent P2Y12 inhibitors were comparable between men and women. Given these data, sex should not influence patient selection for the administration of potent P2Y12 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Prompt reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) reduces infarct size and improves survival. However, the intuitive link between infarct size and prognosis has not been convincingly demonstrated in the contemporary era.Objectives: This study sought to determine the strength of the relationship between infarct size assessed early after primary percutaneous coronary intervention (PCI) in STEMI and subsequent all-cause mortality, reinfarction, and hospitalization for heart failure.Methods: We performed a pooled patient-level analysis from 10 randomized primary PCI trials (total 2,632 patients) in which infarct size was assessed within 1 month after randomization by either cardiac magnetic resonance (CMR) imaging or technetium-99m sestamibi single-photon emission computed tomography (SPECT), with clinical follow-up for ≥ 6 months.Results: Infarct size was assessed by CMR in 1,889 patients (71.8%) and by SPECT in 743 patients (28.2%). Median (25th, 75th percentile) time to infarct size measurement was 4 days (3, 10 days) after STEMI. Median infarct size (% left ventricular myocardial mass) was 17.9% (8.0%, 29.8%), and median duration of clinical follow-up was 352 days (185, 371 days). The Kaplan-Meier estimated 1-year rates of all-cause mortality, reinfarction, and HF hospitalization were 2.2%, 2.5%, and 2.6%, respectively. A strong graded response was present between infarct size (per 5% increase) and subsequent mortality (Cox-adjusted hazard ratio: 1.19 [95% confidence interval: 1.18 to 1.20]; p < 0.0001) and hospitalization for heart failure (adjusted hazard ratio: 1.20 [95% confidence interval: 1.19 to 1.21]; p < 0.0001), independent of age, sex, diabetes, hypertension, hyperlipidemia, current smoking, left anterior descending versus non-left anterior descending infarct vessel, symptom-to-first device time, and baseline TIMI (Thrombolysis In Myocardial Infarction) flow 0/1 versus 2/3. Infarct size was not significantly related to subsequent reinfarction.Conclusions: Infarct size, measured by CMR or technetium-99m sestamibi SPECT within 1 month after primary PCI, is strongly associated with all-cause mortality and hospitalization for HF within 1 year. Infarct size may, therefore, be useful as an endpoint in clinical trials and as an important prognostic measure when caring for patients with STEMI. [ABSTRACT FROM AUTHOR]

Background: Patients with acute coronary syndrome (ACS), especially those receiving medical management without revascularization, are at high risk for spontaneous myocardial infarction (MI), but its frequency and predictors are unknown.Objectives: This study sought to characterize spontaneous MI events in a randomized population during 30 months of follow-up and develop a prediction model for spontaneous MI to assign risk of spontaneous MI events in ACS populations.Methods: We analyzed data from the randomized TRILOGY ACS (TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medically manage Acute Coronary Syndromes) trial of aspirin plus prasugrel or clopidogrel following ACS. The trial included 9,326 patients with non-ST-segment elevation myocardial infarction (NSTEMI)/unstable angina (UA) who were managed medically without planned revascularization. Our study population included 9,294 patients. A multivariable Cox proportional hazards model was developed to determine predictors of time to first spontaneous MI event through 30 months. After model validation, we developed a calculator for model implementation.Results: Among 9,294 patients, 695 spontaneous MI events occurred over a median of 17 months, representing 94% of adjudicated MI events (n = 737). The Kaplan-Meier event rate of spontaneous MI through 30 months was 10.7%. The strongest predictors of spontaneous MI were older age, NSTEMI versus UA as index event, diabetes mellitus, no pre-randomization angiography, and higher baseline creatinine values. The model exhibited good predictive capabilities (c-index = 0.732) and had good calibration, especially for patients with low-to-moderate risk of spontaneous MI.Conclusions: Spontaneous MI following a medically managed UA/NSTEMI event is common. Baseline characteristics can be used to predict subsequent risk of spontaneous MI in this population. These findings provide insight into the long-term natural history of medically managed UA/NSTEMI patients and could be used to optimize risk stratification and treatment of these patients. (A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects [TRILOGY ACS]; NCT00699998). [ABSTRACT FROM AUTHOR]

Background: Certain alleles of the CYP2C19 gene are associated with higher platelet reactivity and increased ischemic events among patients treated with clopidogrel. However, the relationship of CYP2C19 genotype and outcomes in medically managed patients with acute coronary syndromes (ACS) is not known.Objectives: This study sought to assess the effect of CYP2C19 genotype on ischemic outcomes in patients with ACS initially managed medically without revascularization who were randomized to either clopidogrel or prasugrel.Methods: We classified patients as extensive metabolizers (EM) or reduced metabolizers (RM) based on CYP2C19 genotype and evaluated ischemic outcomes and platelet reactivity. Among 9,326 patients enrolled from 2008 to 2011, 5,736 participated in the genetics cohort; of these, 2,236 had platelet function testing data.Results: There was no association between CYP2C19 metabolizer status (EM vs. RM) and the primary composite endpoint of cardiovascular death, myocardial infarction (MI), or stroke (hazard ratio [HR]: 0.86). EM and RM patients had similar rates of the primary endpoint whether treated with prasugrel (HR: 0.82) or clopidogrel (HR: 0.91; p for interaction = 0.495). After adjusting for clinical and treatment variables, EM patients had a lower risk of MI versus RM patients (HR: 0.80), but risks of other outcomes were similar. RM patients had significantly higher mean P2Y12 reaction units versus EM patients when treated with clopidogrel (39.93), but not with prasugrel (3.87).Conclusions: CYP2C19 metabolizer status is not associated with the composite outcome of cardiovascular death, MI, or stroke in medically managed ACS patients treated with clopidogrel or prasugrel. Our findings do not support routine CYP2C19 genetic testing in this population. (A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects [TRILOGY ACS]; NCT00699998). [ABSTRACT FROM AUTHOR]

Background: Pulse pressure (PP) provides valuable prognostic information in specific populations, but few studies have assessed its value on cardiovascular outcomes in a broad, worldwide population.Objectives: The aim of this study was to determine whether PP is associated with major adverse cardiovascular outcomes, independently of mean arterial pressure.Methods: Participants from the international REACH (Reduction of Atherothrombosis for Continued Health) registry, which evaluates subjects with clinical atherothrombotic disease or risk factors for its development, were examined. Those with incomplete 4-year follow-up or PP data (final n = 45,087) were excluded. Univariate and multivariate regression analyses were performed to determine the association between PP and cardiovascular outcomes, including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, all myocardial infarction, all stroke, cardiovascular hospitalization, and a combined outcome. PP was analyzed as a continuous and categorical (i.e., by quartile) variable.Results: The mean age of the cohort was 68 ± 10 years, 35% were women, and 81% were treated for hypertension. The mean blood pressure was 138 ± 19/79 ± 11 mm Hg, rendering a mean PP of 49 ± 16 mm Hg. On univariate analysis, increasing PP quartile was associated with worse outcomes (p < 0.05 for all comparisons). After adjusting for sex, age, current smoking status, history of hypercholesterolemia, history of diabetes, aspirin use, statin use, blood pressure medication use, and mean arterial pressure, PP quartile was still associated with all outcomes except all stroke and cardiovascular death (p < 0.05 for all comparisons). Analysis of PP as a continuous variable yielded similar results.Conclusions: In an international cohort of high-risk subjects, PP, a readily available hemodynamic parameter, is associated with multiple adverse cardiovascular outcomes and provides prognostic utility beyond that of mean arterial pressure. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) has emerged as a therapeutic alternative for patients with symptomatic aortic stenosis at high or prohibitive surgical risk. However, patients undergoing TAVI are also at high risk for both bleeding and stroke complications, and specific mechanical aspects of the procedure itself can increase the risk of these complications. The mechanisms of periprocedural bleeding complications seem to relate mainly to vascular/access site complications (related to the use of large catheters in a very old and frail elderly population), whereas the pathophysiology of cerebrovascular events remains largely unknown. Further, although mechanical complications, especially the interaction between the valve prosthesis and the native aortic valve, may play a major role in events that occur during TAVI, post-procedural events might also be related to a prothrombotic environment or state generated by the implanted valve, the occurrence of atrial arrhythmias, and associated comorbidities. Antithrombotic therapy in the setting of TAVI has been empirically determined, and unfractionated heparin during the procedure followed by dual antiplatelet therapy with aspirin (indefinitely) and clopidogrel (1 to 6 months) is the most commonly recommended treatment. However, bleeding and cerebrovascular events are common; these may be modifiable with optimization of periprocedural and post-procedural pharmacology. Further, as the field of antiplatelet and anticoagulant therapy evolves, potential drug combinations will multiply, introducing variability in treatment. Randomized trials are the best path forward to determine the balance between the efficacy and risks of antithrombotic treatment in this high risk-population. [ABSTRACT FROM AUTHOR]

Early observations of cardiogenic shock as a systemic clinical syndrome were first described in 1942. Today, cardiogenic shock remains the leading cause of death among patients hospitalized for myocardial infarction (MI). Mortality rates in post-MI cardiogenic shock approach 50% despite rapid revascularization, optimal medical care, and use of mechanical support. New therapeutic strategies with global systemic effects may offer advances in treatment and outcome in post-MI cardiogenic shock. Therapeutic hypothermia for post-MI cardiogenic shock has multiple potentially beneficial physiologic effects, including the potential to improve post-ischemic cardiac function and hemodynamics, decrease myocardial damage, and reduce end-organ injury from prolonged hypoperfusion. Available data in animal models of post-MI cardiogenic shock and ischemia/reperfusion injury and small case series of human patients with cardiogenic shock suggest its promise as a potential therapeutic strategy for cardiogenic shock in the post-MI setting. We hypothesize that systemic therapeutic hypothermia could decrease morbidity and mortality in post-MI patients with cardiogenic shock and warrants study a new treatment that could be widely available at hospitals worldwide. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to examine the association between lower socioeconomic status (SES), as ascertained by years of education, and outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI). Background: Previous studies have shown an inverse relationship between SES and coronary heart disease and mortality. Whether a similar association between SES and mortality exists in STEMI patients is unknown. Methods: We evaluated 11,326 patients with STEMI in the GUSTO-III (Global Use of Strategies to Open Occluded Coronary Arteries) trial study from countries that enrolled >500 patients. We evaluated clinical outcomes (adjusted using multivariate regression analysis) according to the number of years of education completed. Results: One-year mortality was inversely related to years of education and was 5-fold higher in patients with <8 years compared with those with >16 years of education (17.5% vs. 3.5%, p < 0.0001). The strength of the relationship between education and mortality varied among different countries. Nonetheless, years of education remained an independent correlate of mortality at day 7 (hazard ratio per year of increase in education: 0.86; 95% confidence interval: 0.83 to 0.88) and also between day 8 and 1 year (hazard ratio per year of increase in education: 0.96; 95% confidence interval: 0.94 to 0.98), even after adjustment for baseline characteristics and country of enrollment. Conclusions: When the number of years of education was used as a measure of SES, there was an inverse relationship such that significantly higher short-term and 1-year mortality existed beyond that accounted for by baseline clinical variables and country of enrollment. Future studies should account for and investigate the mechanisms underlying this link between SES and cardiovascular disease outcomes. [ABSTRACT FROM AUTHOR]

Objectives: We assessed the incidence, predictors, and outcomes of gastrointestinal bleeding (GIB) in patients with acute coronary syndromes (ACS). Background: GIB is a potential hemorrhagic complication in patients with ACS treated with antithrombotic and/or antiplatelet medications. The clinical outcomes associated with GIB in this setting have not been systematically studied. Methods: In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 13,819 patients with moderate- and high-risk ACS, enrolled at 450 centers in 17 countries between August 2003 and December 2005, were randomized to the open-label use of 1 of 3 antithrombin regimens (heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin monotherapy). Results: GIB within 30 days occurred in 178 patients (1.3%). Older age, baseline anemia, longer duration of study drug administration before angiogram, smoking, ST-segment deviation ≥1 mm, and diabetes were identified as independent predictors of GIB. On multivariable analysis, GIB was strongly associated with 30-day all-cause mortality (hazard ratio [HR]: 4.87 [interquartile range (IQR) 2.61 to 9.08], p < 0.0001), cardiac mortality (HR: 5.35 [IQR 2.71 to 10.59], p < 0.0001), and composite ischemia (HR: 1.94 [IQR 1.14 to 3.30], p = 0.014), as well as with 1-year all-cause mortality (HR: 3.97 [IQR 2.64 to 5.99], p < 0.0001), cardiac mortality (HR: 3.77 [IQR 2.14 to 6.63], p < 0.0001), myocardial infarction (HR: 1.74 [IQR 1.01 to 3.02], p = 0.047), and composite ischemia (HR: 1.90 [IQR 1.37 to 2.64], p = 0.0001). Patients who experienced GIB had significantly higher rates of stent thrombosis compared with patients without GIB (5.8% vs. 2.4%, p = 0.009). Conclusions: GIB is a serious condition in the scenario of ACS and is independently associated with mortality and ischemic complications. [Copyright &y& Elsevier]

Objectives: The aim of this study was to evaluate the relative impact of spontaneously occurring and periprocedural myocardial infarction (MI) on survival after percutaneous coronary intervention (PCI). Background: The clinical significance of periprocedural MI after PCI remains uncertain. Methods: Outcomes during a 1-year follow-up were evaluated among 7,773 patients enrolled in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial with a non–ST-segment elevation acute coronary syndrome in whom PCI was performed. Results: Periprocedural MI developed in 466 patients (6.0%), and spontaneous MI unrelated to PCI subsequently developed in 200 patients (2.6%). Patients developing spontaneous and periprocedural MI compared with those patients without MI had significantly greater unadjusted rates of mortality at 30 days (5.0% vs. 3.2% vs. 0.8%, respectively, p < 0.0001) and at 1 year (16.0% vs. 6.0% vs. 2.6%, respectively, p < 0.0001). In a time-updated multivariable analysis, after adjusting for differences in baseline and procedural characteristics between the groups, we found that spontaneous MI was a powerful independent predictor of subsequent mortality (hazard ratio: 7.49, 95% confidence interval: 4.95 to 11.33, p < 0.0001), whereas periprocedural MI was not a significant predictor of mortality (hazard ratio: 1.30, 95% confidence interval: 0.85 to 1.98, p = 0.22). Conclusions: Among patients with acute coronary syndrome undergoing PCI, the spontaneous development of an MI unrelated to PCI is a powerful predictor of subsequent mortality. In contrast, periprocedural MI is a marker of baseline risk, atherosclerosis burden, and procedural complexity but in most cases does not have independent prognostic significance. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158) [Copyright &y& Elsevier]

Objectives: This study sought to evaluate the impact of upstream clopidogrel in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) requiring coronary artery bypass grafting (CABG) from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. Background: Despite benefits of clopidogrel in patients with NSTE-ACS undergoing percutaneous coronary intervention, this agent is often not administered upstream (before angiography) as recommended by the American College of Cardiology/American Heart Association guidelines because of potential bleeding in the minority of patients who require CABG. Methods: The ACUITY trial enrolled 13,819 patients with NSTE-ACS undergoing early invasive management. The timing of clopidogrel initiation was per investigator discretion. A 5-day washout period before CABG was recommended for patients having received clopidogrel. Results: Of 13,819 patients enrolled, 1,539 (11.1%) underwent CABG before discharge. Clopidogrel-exposed patients had a longer median duration of hospitalization (12.0 days vs. 8.9 days, p < 0.0001), but fewer adverse composite ischemic events (death, myocardial infarction, or unplanned revascularization) at 30 days; 12.7% vs. 17.3%, p = 0.01), with nonsignificantly different rates of non–CABG-related major bleeding (3.4% vs. 3.2%, p = 0.87) and post-CABG major bleeding (50.3% vs. 50.9%, p = 0.83) compared with those patients not administered clopidogrel. By multivariable analysis, clopidogrel use before CABG was an independent predictor of reduced 30-day composite ischemia (odds ratio: 0.67, 95% confidence interval: 0.48 to 0.92, p = 0.001) but not of increased post-CABG major bleeding (odds ratio: 0.98, 95% confidence interval: 0.80 to 1.19, p = 0.80). Conclusions: Clopidogrel administration before catheterization in patients with NSTE-ACS requiring CABG is associated with significantly fewer 30-day adverse ischemic events without significantly increasing major bleeding, compared to withholding clopidogrel until after angiography. These findings support the American College of Cardiology/American Heart Association guidelines for upstream clopidogrel administration in all NSTE-ACS patients, including those who subsequently undergo CABG. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158). [Copyright &y& Elsevier]

Objectives: This study sought to evaluate the impact of age on outcomes in patients with moderate- and high-risk non–ST-segment elevation acute coronary syndrome (NSTE-ACS) enrolled in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. Background: Aging-associated changes in physiology and metabolism may alter the risk and benefit of therapeutic strategies from that observed in younger people. Methods: We performed a pre-specified analysis of 30-day and 1-year outcomes in 4 age groups, overall and among those undergoing percutaneous coronary intervention (PCI). Results: Of 13,819 patients in the ACUITY trial, 3,655 (26.4%) were <55 years of age, 3,940 (28.5%) were 55 to 64 years of age, 3,783 (27.4%) were 65 to 74 years of age, and 2,441 (17.7%) were ≥75 years of age. Older patients had more cardiovascular risk factors and had a higher acuity at presentation. Patients age ≥75 years treated with bivalirudin alone had similar ischemic outcomes, but significantly lower rates of bleeding compared with those treated with heparin and glycoprotein IIb/IIIa inhibitors overall and in the PCI subset. The number needed to treat with bivalirudin alone to avoid 1 major bleeding event was lower in this age group (23 overall and 16 for PCI-treated patients) than in any other. Conclusions: Ischemic and bleeding complications after NSTE-ACS increase with age. Although ischemic event rates are not statistically different with either bivalirudin alone or a heparin plus glycoprotein IIb/IIIa inhibitor, bleeding complications are significantly less frequent with bivalirudin alone. Because of the substantial risk of bleeding in patients age ≥75 years, the number needed to treat to avoid 1 major bleeding event using bivalirudin alone was the lowest in the elderly group, especially among those undergoing PCI. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158) [Copyright &y& Elsevier]

Objectives: The aim of this study was to determine the economic impact of several anticoagulation strategies for moderate- and high-risk non–ST-segment elevation acute coronary syndrome (NSTE-ACS) patients managed invasively. Background: The ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial demonstrated that bivalirudin monotherapy yields similar rates of ischemic complications and less bleeding than regimens incorporating glycoprotein IIb/IIIa receptor inhibitors (GPI) for moderate- and high-risk NSTE-ACS. Methods: In ACUITY, 7,851 U.S. patients were randomized to: 1) heparin (unfractionated or enoxaparin) + GPI; 2) bivalirudin + GPI; or 3) bivalirudin monotherapy. Patients assigned to GPI were also randomized to upstream GPI before catheterization or selective GPI only with percutaneous coronary intervention. Resource use data were collected prospectively through 30-day follow-up. Costs were estimated with standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Results: At 30 days, ischemic events were similar for all groups. Major bleeding was reduced with bivalirudin monotherapy compared with heparin + GPI or bivalirudin + GPI (p < 0.001). Length of stay was lowest with bivalirudin monotherapy or bivalirudin + catheterization laboratory GPI (p = 0.02). Despite higher drug costs, aggregate hospital stay costs were lowest with bivalirudin monotherapy (mean difference range: $184 to $1,081, p < 0.001 for overall comparison) and at 30 days (mean difference range: $123 to $938, p = 0.005). Regression modeling demonstrated that hospital savings were primarily due to less major and minor bleeding with bivalirudin ($8,658/event and $2,282/event, respectively). Conclusions: Among U.S. patients in the ACUITY trial, bivalirudin monotherapy compared with heparin + GPI resulted in similar protection from ischemic events, reduced bleeding, and shorter length of stay. Despite higher drug costs, aggregate hospital and 30-day costs were lowest with bivalirudin monotherapy. Thus bivalirudin monotherapy seems to be an economically attractive alternative to heparin + GPI for patients with moderate- and high-risk NSTE-ACS. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158) [Copyright &y& Elsevier]

Objectives: Because excess adiposity is one of the most important determinants of adipokines and inflammatory factors associated with coronary plaque rupture, we hypothesized that obesity was associated with myocardial infarction at earlier ages. Background: The developing obesity pandemic of the past 50 years has gained considerable attention as a major public health threat. Methods: The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) registry was a voluntary observational data collection and quality improvement initiative that began in November 2001, with retrospective data collection from January 2001 to January 2007. The CRUSADE initiative included high-risk patients with unstable angina and non–ST-segment elevation myocardial infarction (NSTEMI). We retrospectively examined, among 189,065 patients with acute coronary syndrome (between January 2001 and September 2006) in the CRUSADE initiative, the relationship of body mass index (BMI) with patient age of first NSTEMI. Results: A total of 111,847 patients with NSTEMI were included in the final analysis. There was a strong, inverse linear relationship between BMI and earlier age of first NSTEMI. The mean patient ages (± SD) of first NSTEMI were 74.6 ± 14.3 years and 58.7 ± 12.5 years for the leanest (BMI ≤18.5 kg/m2) and most obese (BMI >40.0 kg/m2) cohorts, respectively (p < 0.0001). After adjustment for baseline demographic data, cardiac risk factors, and medications, the age of first NSTEMI occurred 3.5, 6.8, 9.4, and 12.0 years earlier with ascending levels of adiposity (BMI 25.1 to 30.0, 30.1 to 35.0, 35.1 to 40.0, and >40.0 kg/m2, respectively; referent 18.6 to 25.0 kg/m2) (p < 0.0001 for each estimate). Conclusions: Excess adiposity is strongly related to first NSTEMI occurring prematurely. [Copyright &y& Elsevier]

Objectives: This study was designed to determine the impact of bivalirudin on 1-year outcomes in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).Background: The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial demonstrated that in moderate- and high-risk ACS patients undergoing PCI, bivalirudin alone compared to unfractionated heparin (UFH) or enoxaparin plus a glycoprotein (GP) IIb/IIIa inhibitor resulted in less major bleeding and similar ischemic outcomes at 30 days. The impact of bivalirudin on 1-year outcomes in ACS patients undergoing PCI is unknown.Methods: In the ACUITY trial, 13,819 patients were enrolled, and 7,789 (56.4%) patients had PCI. Composite ischemia (death, myocardial infarction, or unplanned revascularization) and mortality at 1 year were assessed.Results: Among patients undergoing PCI, 2,561, 2,609, and 2,619 were randomized to UFH or enoxaparin plus a GP IIb/IIIa inhibitor, bivalirudin plus a GP IIb/IIIa inhibitor, and bivalirudin monotherapy, respectively. At 1 year, there were no differences in composite ischemia (17.8% vs. 19.4% vs. 19.2%, p = NS) or mortality (3.2% vs. 3.3% vs. 3.1%, p = NS) among the 3 groups, respectively.Conclusions: Bivalirudin compared with UFH or enoxaparin plus a GP IIb/IIIa inhibitor results in similar rates of composite ischemia and mortality at 1 year in moderate- and high-risk ACS patients undergoing PCI. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to compare outcomes in patients receiving consistent unfractionated heparin (UFH)/enoxaparin (ENOX) therapy and in those switched at randomization to bivalirudin monotherapy. Background: Crossover between UFH and ENOX has been associated with increased adverse outcomes in patients with acute coronary syndromes. The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial demonstrated superior net clinical outcomes with similar rates of ischemia and significantly less major bleeding with bivalirudin monotherapy compared with UFH/ENOX plus a glycoprotein (GP) IIb/IIIa inhibitor. It is unknown if these results would be preserved in patients switched from UFH/ENOX to bivalirudin monotherapy. Methods: We compared composite ischemia, major bleeding, and net clinical outcomes at 30 days in patients receiving consistent UFH/ENOX therapy and in those switched at randomization from pre-treatment with UFH/ENOX to bivalirudin monotherapy. We also compared outcomes in patients naive to antithrombin therapy who were randomized to UFH/ENOX or bivalirudin monotherapy. Results: Two thousand one hundred thirty-seven patients received consistent UFH/ENOX (UFH n = 1,294, ENOX n = 843), and 2,078 patients pre-treated with UFH/ENOX were switched to bivalirudin. Patients switching to bivalirudin had similar rates of ischemia (6.9% vs. 7.4%, p = 0.52), less major bleeding (2.8% vs. 5.8%, p < 0.01), and improved net clinical outcomes (9.2% vs. 11.9%, p < 0.01) than those on consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy who were administered bivalirudin (n = 1,427) had similar rates of ischemia (6.2% vs. 5.5%, p = 0.47), less major bleeding (2.5% vs. 4.9%, p < 0.001), and similar net clinical outcomes (8.0% vs. 9.4%, p = 0.17) compared with naive patients administered UFH/ENOX plus a GP IIb/IIIa inhibitor (n = 1,462). Conclusions: Switching from UFH/ENOX to bivalirudin monotherapy results in comparable ischemic outcomes and an approximately 50% reduction in major bleeding compared with consistent UFH/ENOX plus a GP IIb/IIIa inhibitor. Patients naive to antithrombin therapy administered bivalirudin monotherapy had a significant reduction in bleeding and similar rates of ischemia compared with naive patients initiated with UFH or ENOX plus a GP IIb/IIIa inhibitor. [Copyright &y& Elsevier]

Objectives: We sought to evaluate clinical outcomes of patients with diabetes mellitus in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, overall and by treatment arm. Background: In the ACUITY trial, 13,819 patients with moderate- or high-risk acute coronary syndromes (ACS) were randomized to heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy. Compared with heparin plus GPI, bivalirudin monotherapy resulted in similar protection from ischemic events with less major bleeding. Whether these results apply to patients with diabetes is unknown. Methods: We evaluated the impact of diabetes on 30-day net adverse clinical outcomes (composite ischemia [death, myocardial infarction, or unplanned ischemic revascularization] or major bleeding), overall and by antithrombotic strategy. Results: Diabetes was present in 3,852 randomized patients (27.9%). Compared with nondiabetic patients, diabetic patients had higher 30-day rates of net adverse clinical outcomes (12.9% vs. 10.6%; p < 0.001), composite ischemia (8.7% vs. 7.2%; p = 0.003), and major bleeding (5.7% vs. 4.2%; p < 0.001). Among diabetic patients, compared with heparin plus GPI, bivalirudin plus GPI resulted in similar rates of net adverse clinical outcomes (14.0% vs. 13.8%; p = 0.89), while bivalirudin monotherapy resulted in a similar rate of composite ischemia (7.9% vs. 8.9%; p = 0.39) and less major bleeding (3.7% vs. 7.1%; p < 0.001), yielding fewer net adverse clinical outcomes (10.9% vs. 13.8%; p = 0.02). Conclusions: Diabetic patients with ACS managed invasively have higher rates of composite ischemia and major bleeding. Compared with treatment with heparin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding, resulting in a significant reduction in net adverse clinical outcomes. [Copyright &y& Elsevier]

Objectives: Our purpose was to compare formulae for estimating glomerular filtration rate (GFR) in non–ST-segment elevation acute coronary syndromes (NSTE ACS) patients. Background: Assessment of GFR is important for antithrombotic dose adjustment in NSTE ACS patients. Methods: We assessed estimated glomerular filtration rate (eGFR) with Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD) formulae in 46,942 NSTE ACS patients from 408 CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines) hospitals. Formula agreement was shown continuously and by chronic kidney disease (CKD) stages. We determined in-hospital outcomes and the association between antithrombotic dose adjustment and bleeding for moderate CKD as determined by each formula. Results: The median (interquartile range [IQR]) eGFR was 53.2 ml/min (34.7, 75.1 ml/min) by C-G and 65.8 ml/min (47.6, 83.5 ml/min) by MDRD. The mean eGFR was higher with MDRD (∼9.1 ml/min), but this difference was greater in age, weight, and gender subgroups. Chronic kidney disease classification differed in 20% of the population and altered when antithrombotic dose adjustment was required by C-G versus MDRD (eptifibatide: 45.7% vs. 27.3%; enoxaparin: 19.0% vs. 9.6%). Conclusions: Important CKD disagreements occur in ∼20% of acute coronary syndrome patients, affecting dosing adjustments in those already susceptible to bleeding. Dosing based on C-G formula is preferable, particularly in the small, female, or elderly patient. [Copyright &y& Elsevier]

Over the past decade, there has been a progressive evolution of cardiac marker testing in patients with acute coronary syndromes (ACS). This has not only resulted in a dramatic shift in how we view the diagnosis of myocardial infarction (MI), but it has also extended the role of cardiac marker testing into risk stratification and guidance of treatment decisions. By the year 2000, the development of highly sensitive and cardiac-specific troponin assays had resulted in a consensus change in the definition of MI, placing increased emphasis on cardiac-marker testing with troponins as the new gold standard. Furthermore, and perhaps more importantly, the role of the troponins as superior markers of subsequent cardiac risk in ACS patients became firmly established. Most recently, the supportive role of these markers in identifying patients with ACS who may derive particular benefit from potent anti-thrombotic and anti-platelet therapy or early invasive treatment strategies has been demonstrated. This paper will review the evolution of these important roles of troponin testing for risk stratification in ACS. [Copyright &y& Elsevier]

Objectives: We sought to determine whether for-profit status influenced hospitals’ care or outcomes among non–ST-segment elevation myocardial infarction (NSTEMI) patients. Background: While for-profit hospitals potentially have financial incentives to selectively care for younger, healthier patients, perform highly reimbursed procedures, reduce costs by limiting access to expensive medications, and encourage shorter in-patient length of stay, there are limited data available to investigate these issues objectively. Methods: Using data from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines) Initiative, we investigated whether for-profit status influenced hospitals’ patient case mix, care, or outcomes among 145,357 patients with NSTEMI treated between January 1, 2001, and December 31, 2005, at 532 U.S. hospitals. Impact of for-profit status on care and outcomes was analyzed overall and after adjustment for clinical and facility factors using regression modeling. Results: Patients (n = 11,658) treated at 58 for-profit hospitals were of similar age and gender, but were more likely to be nonwhite (black, Asian, Hispanic, and other) and have health maintenance organization/private insurance, diabetes mellitus, congestive heart failure, hypertension, and renal insufficiency compared with 133,699 patients treated at 474 nonprofit hospitals. For-profit hospitals were less likely to use discharge beta-blockers, but all other treatments were similar including the use of interventional procedures (cardiac catheterization and revascularization procedures) compared with nonprofit centers. In-hospital length of stay and mortality were also similar by hospital type. Conclusions: We found no evidence that for-profit hospitals selectively treat less sick patients, provide less evidence-based care, limit in-hospital stays, or have patients with worse acute outcomes than nonprofit centers. [Copyright &y& Elsevier]

Objectives: The goal of this work was to explore the treatment and outcomes of patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) age ≥90 years. Background: The elderly are often excluded from clinical trials of NSTE-ACS and are underrepresented in clinical registries. Methods: We used data from the CRUSADE registry to study 5,557 patients with NSTE-ACS age ≥90 years and compared their baseline characteristics, treatment patterns, and in-hospital outcomes with a cohort age 75 to 89 years (n = 46,270). Results: Although both groups had much in common, compared with the younger elderly, the older elderly were less likely to be diabetic, smokers, or obese. Among patients without contraindications, the older elderly were less likely to receive glycoprotein IIb/IIIa inhibitors and statins during the first 24 h and were less likely to undergo cardiac catheterization within 48 h. The older elderly were more likely to die (12.0% vs. 7.8%) and experienced more frequent adverse events (26.8% vs. 21.3%) during the hospitalization—differences that persisted after adjustment for baseline patient and hospital characteristics. Increasing adherence to guideline-recommended therapies was associated with both increased bleeding and a graded reduction in risk-adjusted in-hospital mortality across both age groups. Conclusions: In this large population of nonagenarians and centenarians with NSTE-ACS, increasing adherence to guideline-recommended therapies was associated with decreased mortality. These findings reinforce the importance of optimizing care patterns for even the oldest patients with NSTE-ACS, while examining novel approaches to reduce the risk of bleeding in this rapidly expanding patient population. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to determine the predictors of major bleeding and the impact of major bleeding on outcomes, including mortality, in acute coronary syndromes (ACS). Background: Whether major bleeding independently predicts mortality in patients with ACS undergoing an early invasive strategy is undefined. Methods: Patients (n = 13,819) with moderate- and high-risk ACS were randomized to heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy (plus provisional GPI). Logistic regression was used to determine predictors of 30-day major bleeding and mortality. Results: Major bleeding rates in patients treated with heparin plus GPI were higher versus bivalirudin monotherapy (5.7% vs. 3.0%, p < 0.001) and similar versus bivalirudin plus GPI (5.7% vs. 5.3%, p = 0.38). Independent predictors of major bleeding were advanced age, female gender, diabetes, hypertension, renal insufficiency, anemia, no prior percutaneous coronary intervention, cardiac biomarker elevation, ST-segment deviation ≥1 mm, and treatment with heparin plus GPI versus bivalirudin monotherapy. Patients with major bleeding had higher 30-day rates of mortality (7.3% vs. 1.2%, p < 0.0001), composite ischemia (23.1% vs. 6.8%, p < 0.0001), and stent thrombosis (3.4% vs. 0.6%, p < 0.0001) versus those without major bleeding. Major bleeding was an independent predictor of 30-day mortality (odds ratio 7.55, 95% confidence interval 4.68 to 12.18, p < 0.0001). Conclusions: Major bleeding is a powerful independent predictor of 30-day mortality in patients with ACS managed invasively. Several factors independently predict major bleeding, including treatment with heparin plus GPI compared with bivalirudin monotherapy. Knowledge of these findings might be useful to reduce bleeding risk and improve outcomes in ACS. [Copyright &y& Elsevier]

Objectives: We sought to characterize patterns of clopidogrel use before coronary artery bypass grafting (CABG) and examine the drug’s impact on risks for postoperative transfusions among patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS). Background: Adherence in community practice to American College of Cardiology/American Heart Association guidelines for clopidogrel use among NSTE ACS patients has not been previously characterized. Methods: We evaluated 2,858 NSTE ACS patients undergoing CABG at 264 hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Initiative. We examined the patterns of acute clopidogrel therapy and its association with bleeding risks among those having “early” CABG ≤5 days and again among those having “late” surgery >5 days after catheterization. Results: Within 24 h of admission, 852 patients (30%) received clopidogrel. In contrast to national guidelines, 87% of clopidogrel-treated patients underwent CABG ≤5 days after treatment. Among those receiving CABG within ≤5 days of last treatment, the use of clopidogrel was associated with a significant increase in blood transfusions (65.0% vs. 56.9%, adjusted odds ratio [OR] 1.36, 95% confidence interval [CI] 1.10 to 1.68) as well as the need for transfusion of ≥4 U of blood (27.7% vs. 18.4%, OR 1.70, 95% CI 1.32 to 2.19). In contrast, acute clopidogrel therapy was not associated with higher bleeding risks if CABG was delayed >5 days (adjusted OR 1.18, 95% CI 0.54 to 2.58). Conclusions: Despite guideline recommendations, the overwhelming majority of NSTE ACS patients treated with acute clopidogrel needing CABG have their surgery within ≤5 days of treatment. A failure to delay surgery is associated with increased blood transfusion requirements that must be weighed against the potential clinical and economic impacts of such delays. [Copyright &y& Elsevier]

Objectives: We sought to evaluate the association between discordant cardiac marker results and in-hospital mortality and treatment patterns in patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS). Background: Creatine kinase-MB (CK-MB) and cardiac troponins (cTn) are often measured concurrently in patients with NSTE ACS. The significance of discordant CK-MB and cTn results is unknown. Methods: Among 29,357 ACS patients in the CRUSADE initiative who had both CK-MB and cTn measured during the first 36 hours, we examined relationships of four marker combinations (CK-MB−/cTn−, CK-MB+/cTn−, CK-MB−/cTn+, and CK-MB+/cTn+) with mortality and American College of Cardiology/American Heart Association guidelines-recommended acute care. Results: The CK-MB and cTn results were discordant in 28% of patients (CK-MB+/cTn−, 10%; CK-MB−/cTn+, 18%). In-hospital mortality was 2.7% among CK-MB−/cTn− patients; 3.0%, CK-MB+/cTn−; 4.5%, CK-MB−/cTn+; and 5.9%, CK-MB+/cTn+. After adjustment for other presenting risk factors, patients with CK-MB+/cTn− had a mortality odds ratio (OR) of 1.02 (95% confidence interval [CI] 0.75 to 1.38), those with CK-MB−/cTn+ had an OR of 1.15 (95% CI 0.86 to 1.54), and those with CK-MB+/cTn+ had an OR of 1.53 (95% CI 1.18 to 1.98). Despite variable risk, patients with CK-MB+/cTn− and CK-MB−/cTn+ were treated similarly with early antithrombotic agents and catheter-based interventions. Conclusions: Among patients with NSTE ACS, an elevated troponin level identifies patients at increased acute risk regardless of CK-MB status, but an isolated CK-MB+ status has limited prognostic value. Recognition of these risk differences may contribute to more appropriate early use of antithrombotic therapy and invasive management for all cTn+ patients. [Copyright &y& Elsevier]

Objectives: In a large contemporary population of patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS), we sought to describe blood transfusion rates (overall and in patients who did not undergo coronary artery bypass grafting [CABG]), patient characteristics and practices associated with transfusion, variation among hospitals, and in-hospital outcomes in patients receiving transfusions. Background: The use of antithrombotic agents and invasive procedures reduces ischemic complications but increases risks for bleeding and need for blood transfusion in patients with NSTE ACS. Methods: We evaluated patient characteristics and transfusion rates in the overall population (n = 85,111) and determined outcomes and factors associated with need for transfusion in a subpopulation of patients who did not undergo CABG (n = 74,271) from 478 U.S. hospitals between January 1, 2001, and March 31, 2004. Results: A total of 14.9% of the overall and 10.3% of the non-CABG population underwent transfusion during their hospitalization. Renal insufficiency and advanced age were strongly associated with the likelihood of transfusion. Interhospital transfusion rates varied significantly. Non-CABG patients who received transfusions had a greater risk of death (11.5% vs. 3.8%) and death or reinfarction (13.4% vs. 5.8%) than patients who did not undergo transfusion. Conclusions: Transfusion is common in the setting of NSTE ACS, and patients who undergo transfusion are sicker at baseline and experience a higher risk of adverse outcomes than their nontransfused counterparts. Given the wide variation in transfusion practice, further efforts to understand patient and process factors that result in bleeding and need for transfusion in NSTE ACS are needed. [Copyright &y& Elsevier]