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The natural history of patients hospitalized for acute coronary syndrome (ACS) with pre-existing versus (vs) de novo heart failure (HF) has not been previously reported over an extended duration of follow-up. The IMPROVE-IT trial enrolled 18,144 patients hospitalized for ACS and randomized them to combination simvastatin (40 mg)/ezetimibe (10 mg) vs simvastatin (40 mg). Subjects were divided into 3 groups: pre-existing HF (i.e., defined by past medical history), de novo HF (i.e., defined by Killip class II or greater during index admission), and no HF. The final analytical cohort included 14,792 patients (82%) with HF status recorded at baseline. In total, 790 patients (5.3%) reported a pre-existing diagnosis of HF and 1374 patients (9.3%) experienced de novo HF. Patients with pre-existing or de novo HF were older, more likely to be woman, and had a greater prevalence of atrial fibrillation and diabetes mellitus. The incidences of death/HF-hospitalizations at 5 years were 32%/20% for pre-existing HF, 18%/7% for de novo HF, and 8%/3% for no HF. After adjusting for potential confounders, a history of pre-existing or de novo HF was independently associated with increased risk of death (pre-existing HF: hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.68 to 2.22, p < 0.001; de novo HF: HR 1.51, 95% CI 1.33 to 1.72, p < 0.001) and hospitalizations for HF (pre-existing HF: HR 2.96, 95% CI 2.36 to 3.71, p < 0.001; de novo HF: HR 1.88, 95% CI 1.49 to 2.38, p < 0.001). There was no interaction among baseline HF status (i.e., pre-existing or de novo), lipid lowering therapy (i.e., simvastatin/ezetimibe vs simvastatin alone), and clinical outcomes. In conclusion, patients hospitalized for ACS with pre-existing or de novo HF were older and had a greater burden of medical co-morbidities. In conclusion, HF was independently associated with increased risk of long-term morbidity and mortality with the pre-existing HF cohort demonstrating the highest overall risk., (Copyright © 2018. Published by Elsevier Inc.)

Background: Contemporary studies suggest an association between venous thromboembolism and a higher incidence of major cardiovascular events, mostly attributed to arterial atherothrombosis. Using data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, we assessed the association of venous thromboembolism with major cardiovascular events., Methods: In NAVIGATOR, patients with impaired glucose tolerance were randomly allocated to receive valsartan or placebo and nateglinide or placebo in addition to lifestyle modification. Baseline characteristics and prior history of venous thromboembolism were assessed. After adjusting for important baseline covariates, Cox proportional hazards regression models were used to assess the association between venous thromboembolism and major cardiovascular outcomes., Results: Of the 9306 patients enrolled, 129 (1.4%) had a history of venous thromboembolism. Patients with venous thromboembolism were older, more frequently white and female, and had a higher body mass index. Patients with venous thromboembolism had higher 5-year event rates for the composite of death, myocardial infarction, and stroke, as compared with patients without venous thromboembolism (10.7% vs 5.9%; P < .001; adjusted hazard ratio 2.12; 95% confidence interval, 1.36-3.31; P = .001)., Conclusion: In patients with impaired glucose tolerance at high risk for cardiovascular events, the prevalence of venous thromboembolism was rare but associated with worse long-term cardiovascular outcomes, including arterial events. Venous thromboembolism is a marker of risk, and attention should be paid to this high-risk group of patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Early administration of glycoprotein IIbIIIa inhibitors results in improved angiographic parameters, including thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count, and TIMI myocardial perfusion grade (TMPG) among patients with ST-segment elevation myocardial infarction. Whether the same is true in the setting of non-ST-segment elevation acute coronary syndrome is unknown. The goal of the early glycoprotein IIbIIIa inhibition in non-ST-segment elevation acute coronary syndrome (EARLY ACS) angiographic substudy was to compare angiographic outcomes among patients with non-ST-segment elevation acute coronary syndrome who were administered early routine versus delayed provisional eptifibatide. Of 9,406 patients in the EARLY ACS trial, 2,066 patients were included in the angiographic substudy (early routine eptifibatide [n=1,042] or early placebo [n=1,024] with delayed provisional eptifibatide after angiography and before percutaneous coronary intervention [PCI]). The angiographic substudy primary end point was the incidence of TMPG 3 before and after PCI. TMPG 3 before (43.7% vs 44.9%, p=0.58) and after PCI (52.4% vs 50.1%, p=0.73) was similar for early routine versus delayed provisional eptifibatide, respectively. Angiographic procedural complications consisting of a composite of loss of side branch, abrupt vessel closure, distal embolization, and no reflow occurred less frequently in early routine group versus delayed provisional group (9.3% vs 13.6%, respectively, p=0.01). In the EARLY ACS angiographic substudy, the use of early routine eptifibatide resulted in fewer angiographic procedural complications. These data provide support for the use of eptifibatide in the catheterization laboratory during high-risk cases merely to prevent angiographic procedural complications., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We used baseline data from the NAVIGATOR trial to (1) identify risk factors for diabetes progression in those with impaired glucose tolerance and high cardiovascular risk, (2) create models predicting 5-year incident diabetes, and (3) provide risk classification tools to guide clinical interventions. Multivariate Cox proportional hazards models estimated 5-year incident diabetes risk and simplified models examined the relative importance of measures of glycemia in assessing diabetes risk. The C-statistic was used to compare models; reclassification analyses compare the models' ability to identify risk groups defined by potential therapies (routine or intensive lifestyle advice or pharmacologic therapy). Diabetes developed in 3,254 (35%) participants over 5 years median follow-up. The full prediction model included fasting and 2-hour glucose and hemoglobin A1c (HbA1c) values but demonstrated only moderate discrimination for diabetes (C = 0.70). Simplified models with only fasting glucose (C = 0.67) or oral glucose tolerance test values (C = 0.68) had higher C statistics than models with HbA1c alone (C = 0.63). The models were unlikely to inappropriately reclassify participants to risk groups that might receive pharmacologic therapy. Our results confirm that in a population with dysglycemia and high cardiovascular risk, traditional risk factors are appropriate predictors and glucose values are better predictors than HbA1c, but discrimination is moderate at best, illustrating the challenges of predicting diabetes in a high-risk population. In conclusion, our novel risk classification paradigm based on potential treatment could be used to guide clinical practice based on cost and availability of screening tests., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Gender-related differences in the incidence of bleeding and its relation to subsequent mortality in patients with ST-segment elevation myocardial infarction (STEMI) treated with fibrinolysis are not well understood. We studied patients with STEMI receiving fibrinolysis enrolled in 6 clinical trials. Outcomes included moderate or severe bleeding defined using Global Utilization of Strategies to Open Occluded Arteries (GUSTO) criteria and adjusted 1-year mortality (excluding deaths in first 24 hours). Moderate or severe bleeding was 1.9-fold higher in women compared to men (13.3% vs 7.1%, p <0.0001). Bleeding remained higher in women even after adjustment for baseline differences (odd ratios 1.52, 95% confidence interval [CI] 1.42 to 1.62). In fact, female gender was second most important prognostic factor (Wald chi-square 153.6) after older age (Wald chi-square 241.2) in the multivariable bleeding model. Overall 1-year mortality was similar in women and men after adjusting for prognostically important baseline differences (hazard ratio [HR] 1.06, 95% CI 0.97 to 1.17). However, after adjustment for baseline confounders and bleeding, female gender was associated with a lower risk of 1-year death. Thus, adjusted 1-year mortality was similar in women compared to men without bleeding (HR 1.08, 95% CI 0.97 to 1.19) but lower in women compared to men with bleeding (HR 0.85, 95% CI 0.73 to 0.98, p for interaction of gender by bleeding = 0.0016). The highest adjusted 1-year mortality was observed in men with bleeding (HR 2.42, 95% CI 2.20 to 2.66) followed by women with bleeding (HR 2.05, 95% CI 1.80 to 2.33) and women without bleeding (HR 1.08, 95% CI 0.97 to 1.19, referent men without bleeding). In conclusion, in patients with fibrinolytic-treated STEMI, women had a higher incidence but lower mortality with bleeding than men. These data highlight the importance of understanding factors associated with gender-related differences in bleeding and represent an opportunity for improving outcomes of women and men with fibrinolytic-treated STEMI., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: studies have shown higher bleeding and mortality rates among African Americans who receive fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI) compared with whites; however, the relationship of bleeding risk to mortality has not been evaluated., Methods: we studied data from 32,260 STEMI patients receiving fibrinolysis enrolled in the US in 5 clinical trials. Bleeding was defined according to criteria from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries study. Main outcome measure was adjusted 1-year mortality., Results: despite younger age (median: 57 years vs 61 years) and fewer comorbidities, moderate or severe bleeding occurred more frequently among African-Americans than whites (16.3% vs 14.1%; P=.0147, adjusted OR 1.36; 95% confidence interval [CI], 1.14-1.62; P=.0006) as did 1-year mortality (11.5% vs 9.4%). African-American race and moderate or severe bleeding were independently related to 1-year mortality (χ(2) 9.02, P=.0003 and 148.58, P<.0001, respectively). Mortality was highest among African Americans with bleeding (hazard ratio [HR] 2.83; 95% CI, 2.08-3.86) followed by whites with bleeding (HR 1.99; 95% CI, 1.78-2.22) and African Americans without bleeding (HR 1.33; 95% CI, 1.02-1.73) (referent whites without bleeding)., Conclusions: in STEMI patients receiving fibrinolysis, moderate or severe bleeding and mortality were significantly higher in African Americans compared with whites. Bleeding was associated with similarly increased mortality risk in both groups., (2011 Elsevier Inc. All rights reserved.)

Whether prognosis differs in acute renal failure (ARF) after coronary artery bypass grafting (CABG) in patients with and without recovery of renal function is not known. We studied patients who had CABG at Duke University Medical Center (1995 to 2008). ARF was defined as an increase in peak creatinine ≥50% after CABG or ≥0.7 mg/dl above baseline or need for new dialysis. Patients were categorized into 3 groups: (1) no ARF after CABG, (2) ARF after CABG and completely recovered renal function at day 7 (return of creatinine to no higher than baseline and no dialysis), or (3) ARF after CABG with no recovery of renal function at day 7 (creatinine no higher than baseline or new dialysis). Main outcome measurement was risk-adjusted long-term mortality (excluding death ≤7 days). ARF after CABG occurred in 2,083 of 10,415 patients (20%) and completely recovered in 703 (33.7%). Risk-adjusted mortality was highest in patients with ARF without recovery of renal function (hazard ratios 1.47, 95% confidence interval 1.34 to 1.62) and intermediate in those with ARF but completely recovered renal function (hazard ratios 1.21, 95% confidence interval 1.07 to 1.37, referent no-ARF group). Mortality was lower in patients with ARF compared to those without complete recovery of renal function (p = 0.0083). In conclusion, in patients with ARF after CABG, complete recovery of renal function was associated with significantly lower long-term mortality compared to those without such recovery, although this was significantly higher than in those without ARF. Thus, major emphasis should be on prevention of ARF in patients undergoing CABG., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Despite its proven efficacy, low cost, and wide availability, aspirin remains underused. We examined current aspirin use and determined factors that influence its use among outpatients in the United States (US). The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective, longitudinal study of >68,000 outpatients with established atherothrombosis or >or=3 atherothrombotic risk factors. The rates of aspirin use were compared in various patient subgroups. Multivariate logistic regression models were constructed to determine the factors influencing the baseline use of aspirin and other antithrombotic agents in the US population. Approximately 70% of 25,686 US outpatients were treated with aspirin, with greater use in the Midwest and among men, whites, and those aged <65 years. Among aspirin users, 18% took other antiplatelet agents and 6% took oral anticoagulants. Low-dose aspirin (

The currently available sudden cardiac death (SCD) risk prediction tools fail to identify most at-risk patients and cannot delineate a specific patient's SCD risk. We sought to develop a tool to improve the risk stratification of patients with coronary artery disease. Clinical, demographic, and angiographic characteristics were evaluated among 37,258 patients who had undergone coronary angiography from January 1, 1985 to May 31, 2005, and who were found to have at least one native coronary artery stenosis of > or =75%. After a median follow-up of 6.2 years, SCD had occurred in 1,568 patients, 14,078 patients had died from other causes, and 21,612 patients remained alive. A Cox proportional hazards model identified 10 independent patient characteristic variables significantly associated with SCD. A simplified model accounting for 97% of the predictive capacity of the full model included the following 7 variables: depressed left ventricular ejection fraction, number of diseased coronary arteries, diabetes mellitus, hypertension, heart failure, cerebrovascular disease, and tobacco use. The Duke SCD risk score was created from the simplified model to predict the likelihood of SCD among patients with coronary artery disease. It was internally validated with bootstrapping (c-index = 0.75, chi-square = 1,220.8) and externally validated in patients with ischemic cardiomyopathy from the Sudden Cardiac Death Heart Failure Trial (SCD-HeFT) database (c-index = 0.64, chi-square = 14.1). In conclusion, the Duke SCD risk score represents a simple, validated method for predicting the risk of SCD among patients with coronary artery disease and might be useful for directing treatment strategies designed to mitigate the risk of SCD.

The effect of nonstandardized creatine kinase (CK)-MB assays on the assessment of myocardial infarction (MI) end points in multicenter international trials has not been evaluated. We compared the site-reported and corresponding core laboratory CK-MB measures from 5 countries participating in the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial. Samples for CK-MB were collected locally, with corresponding samples sent to a core laboratory at enrollment and after recurrent ischemic events, percutaneous coronary intervention, or coronary artery bypass grafting. The measured values were compared to the reported assay upper limits of normal (ULN) used at the site (or core laboratory for the core laboratory samples). The CK-MB results were available locally and from the core laboratory for 913 patients, constituting 4,693 time-matched laboratory values. The agreement between the core and site laboratory CK-MB/ULN ratio was moderate (concordance correlation coefficient 0.45) and varied considerably by geographic location and site. The CK-MB values were elevated (>or=2 times the ULN) by the core laboratory but normal (<2 times the ULN) by local standards in 708 instances (15%). There were 162 MI end points according to the core laboratory values versus 91 MI end points using the site-reported CK-MB data (kappa statistic 0.48). Compared with patients with no MI by the core or site laboratory values, patients with MI, as determined by both the core and the site laboratories, had significantly lower unadjusted 1-year survival rates (80.6% vs 93.5%, p <0.0001). Patients with MI, as determined by the core laboratory but not by the site laboratory, showed a trend toward a lower 1-year survival rate (89.8% vs 93.5%, p = 0.20). In conclusion, a substantial variation in CK-MB ratios and MI outcomes between the site and core laboratory data was observed in the SYNERGY trial. More MI outcomes were identified by the core laboratory, and patients with MI as defined by core laboratory data had lower 1-year survival, making these events potentially clinically important.

Concern has been raised about combining beta blockers with angiotensin-receptor blockers in patients with heart failure. The VALsartan In Acute myocardial infarction (VALIANT) trial enrolled 14,703 patients with myocardial infarction complicated by heart failure or documented left ventricular systolic dysfunction. These patients were randomly allocated to treatment with valsartan, captopril, or both. Physicians were also encouraged to prescribe beta blockers because of previous evidence of benefit. The baseline characteristics, treatments, and outcomes were compared among 4 groups: patients taking beta blockers at admission only, at discharge only, at both admission and discharge, and neither. Patients treated with beta blockers were at lower risk than those not treated at any period. Those treated with beta blockers at both intervals had a lower 3-year mortality rate (17.7%) than those treated only at randomization (30.7%) or only at discharge (25.9%). The greatest mortality (35.1%) occurred in patients not treated at either point. No statistically significant interaction with prognosis was observed between beta-blocker use and treatment with valsartan or valsartan plus captopril. Patients discharged with a beta blocker had a significant survival advantage after adjustment for differences in baseline characteristics and intervening complications (hazard ratio 0.89, 95% confidence interval 0.81 to 0.98, p = 0.02). This association was most pronounced in patients prescribed consistent beta blockers at randomization and discharge and was present in both patients with impaired and those with preserved systolic left ventricular function. These results have further confirmed that beta blockers reduce the risk of death and nonfatal cardiovascular events in patients with heart failure or systolic left ventricular dysfunction after myocardial infarction. In conclusion, no evidence was found of adverse interactions between the angiotensin-receptor blocker valsartan and beta blockers or of a negative effect of the combination of valsartan, captopril, and beta blockers.

The association of weight loss achieved through various decongestive strategies with clinical outcomes in patients with acute decompensated heart failure (HF) is not well described. The aim of this study was to determine the relation between weight change during hospitalization and subsequent clinical events in patients with decompensated HF. Data from 433 patients hospitalized with advanced HF enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial were evaluated. The influence of change in weight during hospitalization to clinical outcomes (days alive out of the hospital in the first 6 months; death; death or rehospitalization; and death, rehospitalization, or cardiac transplantation) was evaluated. On average, patients lost approximately 3.6 kg during hospitalization. When categorized into 3 weight loss tertiles, those in the highest tertile were more likely to be older, women, and smokers, with higher body weights, previous percutaneous coronary interventions, baseline heart rates, and brain natriuretic peptide and blood urea nitrogen values but lower ejection fractions and peak oxygen consumption. No significant differences were observed between weight change and any in-hospital or follow-up events (days well: hazard ratio 0.995, 95% confidence interval 0.975 to 1.016; 180-day death: hazard ratio 1.012, 95% confidence interval 0.969 to 1.057; death or rehospitalization at 180 days: hazard ratio 1.014, 95% confidence interval 0.990 to 1.038). In conclusion, weight loss in patients with acute decompensated HF during hospitalization was not related to clinical end points. These data challenge the merit of using weight as a surrogate end point for more important clinical events (i.e., death and/or rehospitalization) in patients with HF in the design of treatment strategies for novel therapeutic agents in randomized controlled clinical trials.

Sustained ventricular arrhythmias and heart failure are well-recognized complications after acute myocardial infarction (AMI) and have been associated with worse outcomes and increased mortality. The use of and outcomes associated with acute beta-blocker therapy in patients with AMI complicated by sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and heart failure were investigated. Of 5,391 patients in the VALIANT Registry, sustained VT/VF occurred in 306 (5.7%), with an in-hospital mortality rate of 20.3%. Multivariable logistic regression identified sustained VT/VF as a major predictor of in-hospital death (relative risk 4.18, 95% confidence interval 2.91 to 5.93). Of those with sustained VT/VF, 55.2% were treated with intravenous or oral beta blockade in the first 24 hours. After adjusting for baseline characteristics, propensity for acute beta-blocker use, and the interaction between Killip classification and beta-blocker therapy, beta-blocker therapy within 24 hours was associated with decreased in-hospital mortality in patients with sustained VT/VF (relative risk 0.28, 95% confidence interval 0.10 to 0.75, p = 0.013) without evidence of worsening heart failure. Patients with sustained VT/VF were less likely to receive beta blockers within 24 hours (p = 0.001). In conclusion, sustained VT/VF was common after AMI. In patients with sustained VT/VF, beta-blocker therapy in the first 24 hours after AMI was associated with decreased early mortality without worsening heart failure. Unfortunately, beta blockers were underused acutely in patients with sustained VT/VF.

Despite aspirin's established role in the treatment of atherosclerotic vascular disease, considerable controversy exists regarding its most effective dosing strategy. In a retrospective observational study, we examined the relation between prescribed aspirin dose (<162 mg vs > or =162 mg/day aspirin) and clinical outcome in 4,589 placebo-treated patients enrolled in the Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial over a median follow-up of 366 days. Standard Cox regression analysis was employed because propensity analysis was not feasible. Compared with lower aspirin doses, higher doses were associated with lower unadjusted all-cause mortality (2.9 vs 1.6%, respectively; log rank chi-square 8.6, p = 0.0034). Higher aspirin dose remained independently predictive of lower all-cause mortality in a multivariable Cox proportional hazards model (hazard ratio 0.64, 95% confidence interval 0.42 to 0.97, p = 0.037). However, there was no significant difference in the incidence of the composite endpoint death, nonfatal myocardial infarction, or nonfatal stroke (6.1% vs 6.2%, p = 0.74). Higher aspirin dose was a significant independent predictor of any (hazard ratio 1.32, 95% confidence interval 1.12 to 1.55, p = 0.001) but not serious bleeding. In conclusion, our findings suggest that aspirin doses of > or =162 mg/day may be more beneficial than those <162 mg/day at preventing death.

Myocardial infarction (MI) after coronary artery bypass grafting (CABG) is associated with significant morbidity and mortality. Frequency, management, mechanisms, and angiographic and clinical outcomes associated with perioperative MI remain poorly understood. PREVENT IV was a multicenter, randomized, placebo-controlled trial of edifoligide in 3,014 patients undergoing CABG. Angiographic and 2-year clinical follow-up were complete for 1,920 and 2,956 patients, respectively. Perioperative MI was defined as creatinine kinase-MB increase >or=10 times the upper limit of normal or >or=5 times the upper limit of normal with new 30-ms Q waves within 24 hours of surgery. Baseline characteristics, in-hospital management, and angiographic and clinical outcomes of patients with and without perioperative MI were compared. Perioperative MI occurred in 294 patients (9.8%). Patients with perioperative MI had longer surgery (250 vs 230 minutes; p <0.001), more on-pump surgery (83% vs 78%; p = 0.048), and worse target-artery quality (p <0.001). Patients with perioperative MI more frequently underwent angiography within 30 days of enrollment (1.7% vs 0.6%; p = 0.021). One-year angiographic vein graft failure occurred in 62.4% of patients with and 43.8% of patients without perioperative MI (p <0.001). Two-year composite clinical outcome (death, MI, or revascularization) was worse in patients with perioperative MI before (19.4% vs 15.2%; p = 0.039) and after (hazard ratio 1.33, 95% confidence interval 1.00 to 1.76, p = 0.046) adjusting for differences in significant predictors. In conclusion, perioperative MI was relatively common, was associated with worse outcomes, and mechanisms other than vein graft failure accounted for a substantial proportion of these MIs. Further research is needed into the prevention and treatment of perioperative MI in patients undergoing CABG.

We examined the effects of intensive statin therapy in patients with acute coronary syndromes (ACSs) and previous coronary artery bypass graft surgery (CABG) participating in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22) and the Aggrastat to Zocor (A to Z) trials. Of the 8,655 patients enrolled in PROVE IT-TIMI 22 or A to Z, 640 (7.4%) had undergone CABG before enrollment. After a median follow-up of 2 years, compared with patients without previous CABG, those with previous CABG had a higher risk of cardiovascular death (6.2% vs 2.8%), myocardial infarction (14.2% vs 6.6%), and readmission for ACS (7.9% vs 4.4%, p <0.001 for all comparisons) but a lower rate of repeat coronary revascularization (22.7% vs 26.9%, p = 0.01). Compared with moderate statin therapy, intensive statin therapy appeared to decrease the composite of cardiovascular death, myocardial infarction, stoke, and readmission for an ACS (A to Z primary end point) to a similar extent in patients with (26.1% vs 21.6%, hazard ratio 0.84, p = 0.27) and without (13.9% vs 12.0%, hazard ratio 0.86, p = 0.016) previous CABG, although the decrease was not statistically significant in the previous CABG group, likely due to the small number of patients with previous CABG. In conclusion, compared with patients with ACS without previous CABG, those with previous CABG have a higher risk for adverse cardiac events and may derive similar benefit from intensive statin therapy.

The purpose of this study was to determine international patterns of blood transfusion in patients with acute coronary syndrome (ACS). Previous studies showed geographic heterogeneity in some aspects of ACS care. Data for variability in the use of blood transfusion in ACS management are limited. Pooled data from 3 international randomized trials of patients with non-ST-segment elevation ACS (n = 23,906) were analyzed to determine the association between non-United States (US) location and blood transfusion after stratifying by the use of invasive procedures. The analysis adjusted for differences in patient characteristics and was repeated using a 2-stage mixed-model approach and in patients who underwent in-hospital coronary artery bypass grafting. Compared with US patients, both unadjusted and adjusted hazards for blood transfusion were significantly lower in non-US patients who did not undergo invasive procedures (unadjusted hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.17 to 0.33; adjusted HR 0.20, 95% CI 0.14 to 0.28). This was also true in non-US patients who underwent invasive procedures (unadjusted HR 0.34, 95% CI 0.27 to 0.44; adjusted HR 0.31, 95% CI 0.23 to 0.42). Results were similar in both validation analyses. In conclusion, there was substantial international variation in blood transfusion use in patients with ACS. These results, along with the controversy regarding the appropriate use of transfusion in patients with coronary heart disease, emphasize the need for understanding the role of blood transfusion in the management of patients with ACS and factors that influence transfusion decisions.

Rapid-assay biomarkers may predict outcomes in patients with decompensated heart failure (HF). This study assessed whether rapid-assay B-type natriuretic peptide (BNP) and troponin I predicts length of stay and mortality and correlates with pulmonary artery catheter (PAC)-derived hemodynamics in patients hospitalized with acute HF. There were 141 nonconsecutive patients in this prospective cohort study of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), a randomized trial testing PACs in 433 patients with severe decompensated HF. Biomarkers were drawn at baseline and discharge and when the first, second, and final hemodynamics were obtained in 69 patients randomly assigned to PACs. Cox analysis was used to model mortality, length of stay, and rehospitalization, and Pearson's correlations were used to describe the relation among BNP, troponin I, and PAC-derived hemodynamics. The median (25th percentile, 75th percentile) BNP levels were 783 pg/ml (329, 1,565) at baseline and 468 pg/ml (240, 946) at discharge. After treatment for HF, the median BNP level decreased by 144 pg/ml (-653, 55; p = 0.004). Patients with baseline BNP levels >1,500 pg/ml had greater mortality at 6 months and almost twice the length of stay as patients with BNP levels <500 pg/ml (10.1 vs 5.7 days, p = 0.002). Troponin I did not predict these outcomes. First BNP correlated modestly with first right atrial pressure (r = 0.47, p = 0.005) and first pulmonary capillary wedge pressure (r = 0.54, p = 0.001). Final BNP correlated modestly with final right atrial pressure (r = 0.63, p = 0.001). In conclusion, patients with BNP >1,500 pg/ml had greater mortality and longer length of stay than patients with BNP <500 pg/ml. BNP decreased after hospitalization, but correlated modestly with PAC-derived hemodynamics. Rapid-assay BNP may provide information that helps physicians decide when to pursue more aggressive and invasive therapies.

We have entered a new era of medicine in which both the interest of scientific rigor and pressure from health care purchasers demand increased adoption of empirically based standards of care. Certain therapeutic areas have seen rapid transformation from a model in which care is based on a clinician's intuition to one based on therapies and standards backed by substantial clinical evidence. The condition of non-ST-elevation acute coronary syndromes, a leading cause of death in industrialized nations, provides an excellent example of this transformation and a potential model for other areas of disease treatment. This article discusses the cycle of quality (the conceptual basis for quality improvement in non-ST-elevation acute coronary syndromes), the approach taken by the American College of Cardiology and the American Heart Association in developing their clinical practice guidelines, the use of performance indicators in clinical practice, and the ever-increasing evidence that adherence to practice guidelines and attention to performance measures result in improved patient outcomes.

Compared with moderate lipid lowering with standard-dose statin therapy, intensive lipid lowering with high-dose statin therapy after acute coronary syndromes (ACS) significantly reduces cardiovascular events. However, the 2 trials of high-dose versus standard-dose statin therapy in patients with ACS, Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE-IT-TIMI 22), were not individually powered to evaluate the impact on mortality alone. In this study, a pooled, patient-level analysis of these trials of 8,658 post-ACS patients was performed to provide a more robust estimate of the impact of intensive statin therapy on mortality. By 8 months, achieved low-density lipoprotein levels were lower in the group with intensive statin therapy (median 64 mg/dl, interquartile range 51 to 81) than in the group with moderate statin therapy (median 87 mg/dl, interquartile range 71 to 107) (p <0.001). All-cause mortality was significantly reduced in the group with intensive statin therapy compared with the group with moderate statin therapy (3.6% vs 4.9%, hazard ratio 0.77, 95% confidence interval 0.63 to 0.95, p = 0.015), without significant interaction by trial (interaction p = 0.63). The reduction in all-cause mortality with intensive statin therapy was consistent across key subgroups. In conclusion, in this analysis of >8,600 patients, intensive lipid lowering with high-dose statin therapy after ACS was associated with reduced mortality compared with moderate lipid lowering with standard-dose statin therapy. On the basis of these findings, 1 death was prevented for every 95 patients treated with high-dose statin therapy for 2 years. The results of this pooled analysis provide further evidence for early intensive statin therapy after ACS.

Improved application of existing therapies, directed by evidence-based guidelines, may offer immediate savings of life and function to patients with cardiovascular disease. We sought to evaluate the evidence that use of performance measures derived from clinical practice guidelines is associated with better clinical outcomes in this context. We conducted a search of the MEDLINE database for published studies evaluating the relationship of evidence-based therapies and outcomes in patients with coronary artery disease or heart failure. Studies examined included single-center, regional, national, and international experiences, and varied considerably in design. Most studies linking guidelines-based care to outcomes focused on patients with coronary artery disease; relatively few addressed patients with heart failure. Few studies, all nonrandomized, examined the use of specific interventions to improve quality of care in the context of standardized care tools. Almost all studies showed a strong and "dose-response" association between adherence to guidelines and performance measures and outcomes. Higher quality of care, as documented by better performance based on measures derived from practice guidelines, is associated with improved outcomes in patients with cardiovascular disease.

Older age is associated with worse outcomes in patients with cardiogenic shock complicating ST-elevation myocardial infarction (STEMI). However, significant heterogeneity exists in different age groups with respect to outcomes. Identification of factors that modulate age-related risk of death in patients with cardiogenic shock may help clinical decision making and facilitate patient counseling. Accordingly, we evaluated 761 patients with STEMI who presented with cardiogenic shock and received fibrinolysis. We categorized patients into 3 age groups (<60 years, n = 224; 60 to 75 years, n = 360; and > or = 75 years, n = 177). Death at 30 days occurred in 118 patients <60 years of age (53%), 214 patients 60 to 75 years of age (59%), and 127 patients > or = 75 years of age (72%) with cardiogenic shock. Factors associated with death (per 10-U change) on multivariable analysis were older age (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.23 to 1.66), higher heart rate (OR 1.27, 95% CI 1.19 to 1.35), and lower systolic blood pressure (OR 1.32, 95% CI 1.23 to 1.41, c index 0.79). Important interactions were found with age, heart rate, and systolic blood pressure, suggesting that, although age was a strong independent predictor of death in patients with a heart rate < or = 100 beats/min, it was less strongly related to death in patients with a heart rate >100 beats/min in whom prognosis was uniformly poor. Further, elderly patients with a systolic blood pressure >80 mm Hg had substantial chance of recovery. In contrast, those with a systolic blood pressure < or = 80 mm Hg and heart rate >100 beats/min had 30-day death rates >90% even if they were young. In conclusion, our data suggest that, although elderly patients with cardiogenic shock have poor prognosis, presenting heart rate and systolic blood pressure provide important information to differentiate who may have greater chance of recovery. This information may help physicians in deciding treatment options for patients with cardiogenic shock and counseling them about their risks.

Patients with type 2 diabetes mellitus (DM) and those with impaired glucose tolerance are at increased risk for the development of cardiovascular disease. With an increasing global incidence and prevalence of type 2 DM, and with the 2003 lowering of the glucose threshold required for the diagnosis of impaired glucose tolerance to 100 mg/dl (5.6 mmol/L), the concept of DM prevention, and presumed reduction of cardiovascular risk, is attractive. However, there is little evidence to guide the choice of DM prevention strategy and no certainty that DM prevention will result in reduced cardiovascular events or an overall favorable balance of benefit to risk. In conclusion, this review examines previous reports on DM prevention, with special attention to evidence for cardiovascular event reduction in association with specific interventions to prevent DM.

Management and outcomes of patients with acute coronary syndromes (ACSs) may vary according to patient race and ethnicity. To assess racial differences in presentation and outcome in high-risk North American patients with non-ST-segment elevation (NSTE) ACS, we analyzed baseline racial/ethnic differences and all-cause death or nonfatal myocardial infarction (MI) in 6,077 white, 586 African-American, and 344 Hispanic patients through 30-day, 6-month, and 1-year follow-up. Frequencies of hypertension were 66% for whites, 83% for African-Americans, and 78% for Hispanics (overall p <0.001). Use of angiography was similar across groups. Use of percutaneous coronary intervention (46% for whites, 41% for African-Americans, and 45% for Hispanics, overall p = 0.046) and coronary artery bypass grafting (20% for whites, 16% for African-Americans, and 22% for Hispanics, overall p = 0.044) differed. African-American patients had significantly fewer diseased vessels compared with white patients (p = 0.0001). Thirty-day death or MI was 14% for whites, 10% for African-Americans, and 14% for Hispanics (overall p = 0.034). After adjustment for baseline variables, African-American patients had lower 30-day death or MI compared with white patients (odds ratio 0.73, 95% confidence interval 0.55 to 0.98). There were no differences in 6-month death or MI across racial/ethnic groups. In conclusion, baseline clinical characteristics differed across North American racial/ethnic groups in the SYNERGY trial. African-American patients had significantly better adjusted 30-day outcomes but similar 6-month outcomes compared with white patients.

The National Cholesterol Education Program Adult Treatment Panel III recommends an algorithm to integrate iterative risk-stratification information with low-density lipoprotein (LDL) cholesterol levels to identify candidates for statin therapy. We used the Aggrastat to Zocor (A to Z) trial, in which all patients presented with an acute coronary syndrome (ACS) event in the absence of previous statin therapy, to evaluate the performance of this algorithm. Of 1,750 patients with ACS included in this analysis, 1,126 (64%) had an indication for statin therapy before enrollment and 624 (36%) did not have a statin indication before enrollment. We estimate that initiating statin therapy at moderate dosages (decreasing LDL by 1 mmol/L) according to the National Cholesterol Education Program Adult Treatment Panel III guidelines would have prevented approximately 15% of the ACS events leading to enrollment in the A to Z trial, whereas more intensive statin therapy (decreasing LDL by 1.5 mmol/L) would have prevented >21% of events. Aspirin use before enrollment was reported in only 38% of subjects with a statin indication. In conclusion, these observations represent missed opportunities for primary and secondary prevention and highlight the need for assessment of patient risk and better adherence to existing prevention guidelines.

Purpose: Less is known about the differences in clinical and angiographic features and the outcomes of African Americans with ST-elevation myocardial infarction compared with whites with ST-elevation myocardial infarction. Accordingly, the current study examines the relationship of African American race to patient-related clinical factors, angiographic findings, and clinical events., Methods: We evaluated data from 32419 patients with ST-elevation myocardial infarction who received fibrinolysis. The primary outcomes of interest were 30-day and 5-year mortality., Results: African Americans comprised 5.1% of the study population (1664/32419). Compared with white patients, black patients were younger, were more likely female, had a higher prevalence of coronary risk factors, and were more likely to have higher presenting heart rate, blood pressure, and Killip Class. Coronary angiography rates were similar in the two groups, but blacks were less likely to undergo coronary revascularization. The patency of the infarct-related artery after thrombolysis or mechanical reperfusion was higher in blacks, who were more likely to have no significant coronary artery disease and less likely to have disease in two or more vessels. In-hospital stroke (adjusted odds ratio 1.75, 95% confidence interval [CI] 1.19-2.59) and major bleeding (adjusted odds ratio 1.32, 95% CI 1.13-1.55) were higher among African Americans. Although no differences were observed in the 30-day mortality between the two groups, African Americans who survived to 30 days had higher 5-year mortality than whites (17% vs 12.5%, adjusted hazard ratio 1.63, 95% CI 1.41-1.90)., Conclusions: Although 30-day survival was similar between African Americans and whites with ST-elevation myocardial infarction, in-hospital stroke and bleeding and 5-year mortality among 30-day survivors were significantly higher among blacks despite their younger age.

Bleeding is a complication of current therapies for acute coronary syndrome (ACS). No studies have examined the effect of bleeding events on clinical outcomes. We analyzed pooled data from 4 multicenter, randomized clinical trials of patients who had ACS (n = 26,452) to determine an association between bleeding severity as measured by the GUSTO scale and 30-day and 6-month mortality rates using Cox proportional hazards modeling that incorporated bleeding as a time-dependent covariate. The analysis was repeated to examine procedure- and non-procedure-related bleeding and after censoring at the time of coronary artery bypass grafting. Of all the patients included, 27.6% had > or =1 bleeding episode. Patients who bled were older and sicker at presentation than were those who did not bleed. Unadjusted rates of 30-day and 6-month mortality increased as bleeding severity increased. There were stepwise increases in the adjusted hazards of 30-day mortality (mild bleeding, hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3 to 1.9; moderate bleeding, HR 2.7, 95% CI l 2.3 to 3.4; severe bleeding, HR 10.6, 95% CI 8.3 to 13.6) and 6-month mortality (mild bleeding, HR 1.4, 95% CI 1.2 to 1.6; moderate bleeding, HR 2.1, 95% CI 1.8 to 2.4; severe bleeding, HR 7.5, 95% CI 6.1 to 9.3) as bleeding severity increased. Results were consistent after censoring for coronary artery bypass grafting and for procedure- and non-procedure-related bleeds. In conclusion, the GUSTO bleeding classification identifies patients who are at risk for short- and long-term adverse events. Therapies that minimize bleeding risk and maintain an anticoagulant effect may improve outcomes among patients who have ACS.

Purpose: Obesity is a coronary disease risk factor, but its independent effect on clinical outcomes following acute coronary syndromes has not been quantified. We evaluated the relationship between elevated body mass index (BMI) and 30-day, 90-day, and 1-year clinical outcomes postacute coronary syndromes., Subjects and Methods: Using 15 071 patients (normal weight [BMI = 18.5-24.9 kg/m(2)], overweight [BMI = 25-29.9 kg/m(2)], obese [BMI = 30-34.9 kg/m(2)] or very obese [BMI > or =35 kg/m(2)]) randomized from 1997-1999 in the SYMPHONY (Sibrafiban vs aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes) and 2nd SYMPHONY trials, we evaluated the relationships between BMI and 30-day, 90-day, and 1-year mortality and 30-day and 90-day death or myocardial infarction., Results: Increasing BMI was associated with younger age, multiple comorbidities, and greater cardiac medication and procedure use; however, systolic function and coronary disease extent were similar for all BMI categories. Unadjusted Kaplan-Meier mortality estimates were higher for normal-weight patients than for all other BMI groups. After multivariable adjustment, the 30-day mortality hazard ratios (95% confidence interval [CI]) were: overweight, 0.66 (95% CI: 0.47 to 0.94); obese, 0.61 (95% CI: 0.39 to 0.97); very obese, 0.89 (95% CI: 0.48 to 1.64). Adjusted hazard ratios were similar for 90-day and 1-year mortality. There were no statistically significant differences among BMI groups in 30-day and 90-day death or myocardial infarction (unadjusted or adjusted)., Conclusion: Overweight and obese BMI classifications were associated with better intermediate-term survival after acute coronary syndromes than normal weight and very obese, but death or myocardial infarction rates were similar. Further study is required to understand the apparent association of overweight and moderate obesity with better intermediate-term outcomes.

Data were evaluated for patients with acute ST-elevation myocardial infarction (n = 94,182) enrolled in 6 large clinical trials evaluating the efficacy of various reperfusion strategies. It was found that compared with the tallest quartile, incidences of in-hospital reinfarction, stroke, major bleeding, cardiogenic shock, heart failure, and death in the shortest group were 1.4, 1.7, 1.7, 1.8, 1.9, and 2.4 times greater, respectively. Although a strong inverse association of height was observed with unadjusted 30-day mortality (p <0.001), it was attenuated after adjustment for confounders, including weight, and appeared to be nonlinear, such that for height 165 cm, the OR for a 10-cm increase in height was 0.962 (95% CI 0.896 to 1.033). These data indicate that height-related differences in 30-day mortality are explained in large part by height-related differences in patients' clinical characteristics.

Purpose: To correlate pulmonary artery catheterization (PAC) use and 30-day outcomes and to characterize the use of pulmonary artery catheters among patients with acute coronary syndromes (ACS)., Subjects and Methods: We retrospectively studied 26437 ACS patients from two large multicenter, international randomized clinical trials. Multivariable and causal inference analyses were applied to adjust for differences in baseline risk., Results: PAC was performed in 735 patients (2.8%), with a median time to insertion of 24 hours. Patients undergoing PAC were older (median, 67 vs. 64 years), more often diabetic (25.7% vs.16.2%), and more likely to present with ST-segment elevation (81.6% vs. 70.2%) or Killip class III or IV (7.9% vs. 1.4%). US patients were 3.8 times more likely than non-US patients to undergo PAC. Patients managed with PAC also underwent more procedures, including percutaneous intervention (40.7% vs. 18.1%), coronary artery bypass grafting (12.5% vs. 7.7%), and endotracheal intubation (29.3% vs. 2.2%). Mortality at 30 days was substantially higher among patients with PAC for both unadjusted (odds ratio [OR] 8.7; 95% confidence interval [CI] 7.3-10.2) and adjusted analyses (OR 6.4; 95% CI 5.4-7.6) in all groups except in patients with cardiogenic shock (OR 0.99; 95% CI 0.80-1.23)., Conclusions: PAC was associated with increased mortality, both before and after adjustment for baseline patient differences and subsequent events that may have led to PAC use, except in patients with cardiogenic shock. The definitive role of PAC in managing patients with ACS is still to be determined.

We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.

Noninvasive stress testing provides prognostic information in patients who have suspected coronary artery disease, but limited data are available on the incremental value of myocardial perfusion testing in high-risk patients. We studied 3,275 patients who underwent cardiac catheterization and single-photon emission computed tomographic (SPECT) perfusion imaging. Median follow-up was 3.1 years for death, cardiovascular death, and a composite of cardiovascular death or nonfatal myocardial infarction. Using Cox's proportional hazards regression models, we examined the relation of SPECT summed stress score (SSS) to each outcome. A 1-unit change in SSS was associated with increased risks of 4%, 7%, and 5% for death, cardiovascular death, and death or nonfatal myocardial infarction, respectively (all p <0.0001). To examine the prognostic utility of SPECT, after baseline adjustments, SSS and angiographic results provided incremental prognostic information for each outcome. Thus, SPECT SSS provides information beyond clinical and angiographic data in patients who have known or suspected coronary artery disease. This information may be useful for stratifying patients into multiple risk categories for future cardiovascular events and potentially guiding therapy.

In 1,009 patients with atrial fibrillation and congestive heart failure, the 2-year mortality rate was 31% in patients treated with rate control (n = 505) versus 29% in patients treated with rhythm control (n = 504). After adjusting for differences in baseline characteristics and medications, no significant difference in mortality was found between the 2 groups.

In a nonrandomized feasibility study of therapeutic hypothermia in acute myocardial infarction, 18 patients were treated with endovascular cooling (Alsius, Irvine, California) as adjunctive therapy to primary percutaneous coronary intervention to assess measures of infarct size (area under the curve creatinine kinase-MB and technetium-99m single-photon emission computed tomography sestamibi) and the quality of myocardial perfusion (continuous ST-segment monitoring). Periprocedural endovascular cooling successfully decreased core body temperature (median 33.5 degrees C) and was well tolerated, which supports the evaluation of adjunctive hypothermia in pivotal trials to limit infarct size and decrease reperfusion injury.

Of 592 patients in the Global Utilization of Streptokinase and tPA for Occluded Arteries-I trial who had a stroke during initial hospitalization, the risk for intracranial hemorrhage was significantly greater in those with recent facial or head trauma (odds ratio 13.0, 95% confidence interval 3.4 to 85.5); dementia was additionally associated with an increased risk for intracranial hemorrhage (odds ratio 3.4, 95% confidence interval 1.2 to 10.2). Because facial or head trauma may greatly influence treatment decisions, this risk factor should be incorporated into models designed to estimate the risks and benefits of fibrinolytic therapy.

Purpose: Studies suggest that beta-blockers improve outcomes in heart failure patients and may be cost saving to society. However, many heart failure patients are not treated with beta-blockers. Economic incentives facing hospitals, physicians, payers, and patients may not encourage treatment adoption. We assessed the economic effects of beta-blocker therapy from various perspectives: societal, Medicare, hospital, physician, and patient., Methods: A Markov model of heart failure progression over 5 years was developed. Transition probabilities and the effect of beta-blockers on mortality and hospitalization were based on clinical trial data. Estimates of hospital costs and reimbursement were obtained from the Duke University Medical Center. Physician fees were based on the Medicare fee schedule., Results: Beta-blocker therapy increased survival by 0.3 years per patient and reduced societal costs by US dollars 3959 per patient over 5 years. Medicare costs declined by US dollars 6064 per patient, due primarily to lower hospitalization rates. Unless heart failure admissions could be replaced with other hospitalizations that generated an equal or greater revenue above variable cost, hospital revenue would be negatively affected. Physician revenue from treating heart failure patients would also decline. Patient costs increased with beta-blocker use (US dollars 2113 over 5 years)., Conclusion: Beta-blocker therapy improves the clinical outcomes of heart failure patients and is cost saving to society and Medicare. However, hospitals and physicians have no clear financial incentives to support increased beta-blocker use. Changes in practice patterns could be encouraged by linking reimbursement with evidence-based care and covering patients' medication costs.

Non-ST-segment elevation acute coronary syndromes are a dramatic manifestation of coronary artery disease. Multiple clinical trials have shown that early cardiac catheterization improves clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes. Many antithrombotic agents effectively manage unstable coronary syndromes and serve as adjuncts to percutaneous coronary intervention. Yet, the growing number of pharmacologic agents makes early management of non-ST-segment elevation acute coronary syndromes increasingly complex. We review the current evidence regarding the optimal integration of early antithrombotic and antiplatelet therapies with early coronary angiography and subsequent revascularization.

Purpose: To investigate the prognostic importance of new small Q waves following an acute coronary syndrome., Methods: We assessed 6-month mortality in 10501 patients with non-ST-elevation acute coronary syndromes who had survived 30 days and had both admission and 30-day electrocardiograms. Patients were stratified by whether they had no new Q waves (n = 9447), new 30- to 40-ms Q waves (n = 733), or new > or =40-ms Q waves (n = 321)., Results: Mortality was higher in patients with 30- to 40-ms Q waves than in those with no new Q waves (3.4% [25/733] vs. 2.4% [227/9447], P = 0.005), and even higher in those with > or =40-ms Q waves (5.3% [17/321], P = 0.002). After adjustment for baseline risk predictors, mortality remained higher in patients with new 30- to 40-ms Q waves (odds ratio [OR] = 1.30; 95% confidence interval [CI]: 0.85 to 1.98; P = 0.23) and those with new > or =40-ms Q waves (OR = 1.87; 95% CI: 1.13 to 3.09; P = 0.01)., Conclusion: Patients with new small Q waves following a non-ST-elevation acute coronary syndrome are at increased risk of adverse outcomes. These small Q waves should be considered diagnostic of myocardial infarction. Further research should investigate whether even smaller QRS changes are prognostically important.

We performed a cumulative meta-analysis of available studies to evaluate the effect of intravenous platelet glycoprotein (GP) IIb/IIIa antagonists on survival at 30 days and 6 months after percutaneous coronary intervention (PCI). Compounds that block the GP IIb/IIIa receptor substantially reduce myocardial infarctions (MIs) and repeat revascularization. We included 12 trials, which enrolled 20,186 patients in all, in the analysis. Overall, 30-day mortality was significantly reduced with GP IIb/IIIa inhibition (odds ratio 0.73, 95% confidence interval 0.55 to 0.96, p = 0.024). Although 10 of the 12 trials showed a beneficial effect of GP IIb/IIIa inhibitor treatment on mortality, no individual trial detected a statistically significant mortality benefit. The 30-day mortality benefit became significant at the p <0.05 level with addition of the ADMIRAL trial and was further enhanced by the CADILLAC trial. No significant heterogeneity was detected in the collection of trials. At 6 months, the odds ratio was 0.84 (95% confidence interval 0.69 to 1.03, p = 0.087). This survival benefit amounts to preventing approximately 1 of every 3 deaths that occur within 30 days after PCI, saving 2.8 lives/1,000 patients treated (number needed to treat, 357). Thus, patients who undergo PCI can expect significantly lower 30-day mortality, in addition to known reductions in nonfatal MI and repeat procedures, with GP IIb/IIa inhibition. There also is increasing evidence that mortality reductions are preserved at 6 months.

We studied stent thrombosis in 4,607 patients with acute coronary syndromes who received a coronary stent as part of routine care during 2 trials of aspirin versus sibrafiban for secondary prevention. In these patients, stent thrombosis occurred more often than in previous patients who underwent elective percutaneous coronary intervention. These patients and their outcomes may be more representative of patients with typical acute coronary syndromes undergoing stenting in clinical practice.

To understand predictors of cardiac arrest early in acute myocardial infarction (AMI), for the Thrombolytic Predictive Instrument, we developed a multivariable regression model predicting primary cardiac arrest using time-dependent variables based on a case-control study of emergency department (ED) patients with AMI: 65 cases with sudden cardiac arrest and 258 without cardiac arrest. Within the first hour of AMI symptom onset, adjusting for age, systolic blood pressure, serum potassium, and infarct size, increased risk of cardiac arrest was associated with electrocardiographic prolonged QTc interval and a greater sum of ST-segment elevation. After 1 hour, the effect of ST-segment elevation was much reduced and the effect of the QTc interval was reversed, so prolonged QTc appeared protective. Accordingly, for patients presenting 30 minutes after chest pain onset, compared with a QTc of 0.44, the risk for cardiac arrest for patients with QTc of 0.50 was more than doubled (odds ratio [OR] 2.20, 95% confidence intervals [CI] 1.17 to 4.13), whereas for those presenting after an hour, it was much lower (e.g., at 1.5 hours, OR 0.21, 95% CI 0.06 to 0.73). Patients presenting 30 minutes after chest pain onset with a sum of ST elevation of 20 mm had a threefold higher risk than patients with a sum of ST elevation of 5 mm (OR 3.37, 95% CI 1.83 to 6.20). However, if presenting 1.5 hours after chest pain onset, the risk was barely elevated (OR 1.18; 95% CI 1.09 to 1.29). Thrombolytic therapy was protective, halving the odds of cardiac arrest (OR 0.51, 95% CI 0.27 to 0.93). Thus, the relation of prolonged QTc interval and substantial ST segment elevation to cardiac arrest in AMI may be obscured because patients with these risks are more likely to die soon after AMI onset, before ED presentation, and are thereby unavailable for study. Those with prolonged QTc or substantial ST elevation who survive the initial 1.5-hour period are those less susceptible to these risks.

There has been much debate concerning an invasive versus a conservative strategy for patients with acute coronary syndromes. The purpose of this study was to determine whether early in-hospital catheterization reduced mortality in patients with unstable angina and non-ST-elevation myocardial infarction. We performed a retrospective analysis of data collected in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb trial, which compared hirudin and heparin in patients with acute coronary syndromes. We identified 8011 patients with non-ST-segment elevation myocardial infarction and unstable angina who were enrolled in the trial. The primary endpoints were all-cause mortality at 30 days and 1 year. Data were analyzed with multivariate hazards models and propensity scores.After accounting for inception time bias, there were 7897 patients identified, of whom 4536 patients (57%) underwent invasive therapy and 3361 (43%) underwent conservative therapy. Adjusting for propensity scores, the adjusted 30-day mortality for the invasive group was 2.5% compared with 2.7% in the conservative group (P = 0.92); at 1 year, the invasive group had a 6.2% mortality, versus 8.6% in the conservative group (P = 0.005). In a multivariate analysis that adjusted for other clinical factors, an invasive strategy was associated with lower 1-year mortality (hazard ratio = 0.46; 95% confidence interval: 0.10 to 0.84). In patients presenting with acute coronary syndromes, an invasive strategy is associated with improved survival at 1 year even after adjusting for baseline differences.

Many drugs prolong the QT interval and increase the risk of torsade de pointes. Concurrent use of two or more of these drugs can further increase the risk, but the prevalence of concurrent prescription of QT-prolonging drugs is not known. Using the administrative claims database of a national pharmaceutical benefit manager, we conducted a retrospective cohort study in 4,825,345 subjects aged 18 years or older. After identifying 50 drugs with QT-prolonging potential, and an additional 26 drugs that inhibit the metabolic clearance of QT-prolonging drugs, we measured the frequency of overlapping prescriptions for two or more of these drugs in the outpatient setting in 1999. Nearly 1.1 million subjects (22.8%) filled 4.4 million prescriptions for QT-prolonging drugs. Of these, 103,119 subjects (9.4%) filled overlapping prescriptions for two or more of the drugs or for a QT-prolonging drug and another drug that inhibits its clearance; 7249 subjects (0.7%) filled overlapping prescriptions for three or more of these drugs. Twenty-two percent of subjects who filled overlapping prescriptions were aged 65 or older; 74% were women. Antidepressants were involved in nearly 50% of the cases. Concurrent prescription of QT-prolonging drugs is common in the outpatient setting, and antidepressants are involved in half of these cases. Large pharmaceutical claims databases are useful for detecting potentially harmful prescribing behaviors, but better clinical evidence on medication safety is needed before such a system can be implemented fully.

In the Evaluation of Platelet IIb/IIIa Inhibition in Stenting Trial (EPISTENT), abciximab reduced ischemic complications of stent implantation at 30 days and 6 months. The responsible mechanisms remain unclear. We sought to determine if abciximab decreases ischemic complications by decreasing the incidence of angiographic complications during coronary stenting. In EPISTENT, patients were randomized to stenting with abciximab (abciximab group), stenting with placebo (placebo group), or balloon angioplasty with abciximab. Angiographic complications (including major or minor dissection, distal embolization, thrombus postprocedure, side branch or other vessel occlusion, residual stenosis >50%, transient coronary occlusion, and Thrombolysis In Myocardial Infarction final flow <3) were recorded prospectively. Creatine kinase (CK)-MB enzyme levels after intervention were measured at 6-hour intervals. We analyzed angiographic complications and CK-MB elevations in the abciximab group (n = 784) and the placebo group (n = 803). Angiographic complications were 29% less frequent in the abciximab group compared with the placebo group (17.0% vs 23.8%; p = 0.001). In patients with angiographic complications, there was a nonsignificant reduction in the incidence of CK-MB elevation >3 times normal with abciximab therapy (19.7% vs 24.5% in placebo group; p = 0.314). Abciximab (compared with placebo) significantly reduced the incidence of CK-MB elevation >3 times normal in those without any angiographic complications (6.5% vs 10.7%; p = 0.007). In summary, abciximab (compared with placebo) significantly reduced angiographic complications during coronary stenting. Abciximab also prevented CK-MB elevations in patients without angiographic complications.

For patients undergoing nonurgent coronary stent implantation, blockade of the glycoprotein IIb/IIIa receptor with eptifibatide reduces the incidence of ischemic complications. We evaluated the interaction of eptifibatide with diabetes in patients who underwent this procedure by analyzing the 1-year outcomes of those enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial (466 diabetic and 1,595 nondiabetic patients). At 1 year, the composite end point of death, myocardial infarction (MI), or target vessel revascuarlization (TVR) was higher in diabetic patients (24.5% vs 18.4%; p = 0.008). At 1 year, eptifibatide had a similar effect on the composite end point of death, MI, or TVR in diabetic (hazards ratio [HR] 0.71, 95% confidence interval [CI] 0.49 to 1.04) and nondiabetic patients (HR 0.80, 95% CI 0.63 to 0.99). A similar treatment effect was also seen on death or MI in both groups. The 1-year mortality rate for diabetic patients assigned to placebo was 3.5% versus 1.3% for patients receiving eptifibatide (HR 0.37, 95% CI 0.10 to 1.41); the latter rate was similar to the mortality rate of 1.4% for nondiabetic patients in the eptifibatide group. However, eptifibatide did not have a significant effect on TVR in diabetic patients (HR 0.90, 95% CI 0.57 to 1.41). Our data suggest that treatment with eptifibatide is associated with a similar relative reduction in adverse ischemic complications in diabetic and nondiabetic patients undergoing coronary stent implantation. There is no evidence of a statistical interaction in the treatment effect of eptifibatide between patients with and without diabetes.