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Aims: Patients hospitalized for heart failure (HF) are at high risk for 30-day readmission. This study sought to examine the timings and causes of readmission within 30 days of an HF hospitalization.Methods and Results: Timing and cause of readmission in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure) trial were assessed. Early and late readmissions were defined as admissions occurring within 0-7 days and 8-30 days post-discharge, respectively. Patients who died in hospital or remained hospitalized at day 30 post-randomization were excluded. Patients were compared by timing and cause of readmission. Logistic and Cox proportional hazards regression analyses were used to identify independent risk factors for early vs. late readmission and associations with 180-day outcomes. Of the 6584 patients (92%) in the ASCEND-HF population included in this analysis, 751 patients (11%) were readmitted within 30 days for any cause. Overall, 54% of readmissions were for non-HF causes. The median time to rehospitalization was 11 days (interquartile range: 6-18 days) and 33% of rehospitalizations occurred by day 7. Rehospitalization within 30 days was independently associated with increased risk for 180-day all-cause death [hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.93-2.94; P < 0.001]. Risk for 180-day all-cause death did not differ according to early vs. late readmission (HR 0.99, 95% CI 0.67-1.45; P = 0.94).Conclusions: In this hospitalized HF trial population, a significant majority of 30-day readmissions were for non-HF causes and one-third of readmissions occurred in the first 7 days. Early and late readmissions within the 30-day timeframe were associated with similarly increased risk for death. Continued efforts to optimize multidisciplinary transitional care are warranted to improve rates of early readmission. [ABSTRACT FROM AUTHOR]

ST-segment elevation myocardial infarction (STEMI) remains a significant global public health concern. Practice guidelines in both the United States and Europe have been major contributors to providing evidence-based care. Rapid advances in contemporary therapies mandate regular and timely updates to guideline recommendations. In the fall of 2012, the European Society of Cardiology published their latest guidelines for the management of STEMI. In 2013 (∼3 months later), the American College of Cardiology Foundation and the American Heart Association jointly published their most recent STEMI guideline statements. In this review, we compare the transatlantic guidelines, highlighting differences in their recommendations and the interpretation of evidence addressing STEMI care. [ABSTRACT FROM AUTHOR]

The article determines the international variation in and factors associated with hospital readmission after ST-segment elevation myocardial infarction (STEMI) and country-level care patterns in controlled patients from the U.S., Canada, Australia, New Zealand and European countries from July 13, 2004 to May 11, 2006. Findings revealed the higher readmission rates for the U.S. than other countries, and the shortest median length of hospital stay for U.S. patients and the longest for patients in Germany. Results of multivariable logistic regression analysis identified multivessel disease and U.S. location as independent predictors of readmission but not of in-hospital death or 30-day post-admission death.

The article studies patients treated at hospitals that were part of 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. According to the authors, hospitals that participated in trials had higher adjusted guideline adherence than did nonparticipating hospitals. They add that patients treated at hospitals that participated in trials had significantly lower mortality rates than did patients treated at nonparticipating hospitals.

Focuses on the development of clinical practice guidelines to help physicians make appropriate decisions in the management of cardiology patients in the U.S. Establishment of a joint task force to define the role of specific procedures in the management of cardiovascular disease; Utilization of technology in the treatment of patients; Use of rules of evidence and clinical recommendations.

Comments on issues concerning the law in the U.S., featured in the November 1976 issue of the 'American Bar Association Journal.' View on how tribal courts operate; Retirement policies for lawyers; Bill allowing attorneys' fees in the enforcement of civil rights; Standards of judicial administration in appellate courts; Impact of plea bargaining on the judicial process.

A transformation in ST-segment elevation myocardial infarction (STEMI) care in the United States has unfolded. It asserts superior reperfusion with primary percutaneous coronary intervention (PPCI) over fibrinolysis on the basis of studies showing the former method to be superior for reperfusion of patients with STEMI. Although clear benefit has resulted from national programs directed toward achieving shorter times to PPCI in facilities with around-the-clock access, most patients present to non-PPCI hospitals. Because delay to PPCI for most patients with STEMI presenting to non-PPCI centers remains outside current guidelines, many are denied benefit from pharmacologic therapy. This article describes why this approach creates a treatment paradox in which more effort to improve treatment for patients with PPCI for acute STEMI often leads to unnecessary avoidance and delay in the use of fibrinolysis. Recent evidence confirms the unfavorable consequences of delay to PPCI and that early prehospital fibrinolysis combined with strategic mechanical co-interventions affords excellent outcomes. The authors believe it is time to embrace an integrated dual reperfusion strategy to best serve all patients with STEMI. [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]

This study looks at how patients with coronary heart disease are treated throughout the United States and says that treatment for the condition seems to be different in the New England States than in the rest of the country. It was found that physicians in New England favor the use of beta blockers, nitrates and angiotensin-converting enzyme inhibitors but did not use calcium-channel blockers or lidocaine as frequently as physicians in other region. The proportion of patients undergoing cardiac revascularization procedures such as angiograms, angioplasties and bypass surgery was the lowest in New England. [ABSTRACT FROM AUTHOR]

Background: Much attention has been directed to the use of medical resources and to patients' outcomes in Canada as compared with the United States. We compared U.S. and Canadian patients with respect to their use of medical resources and their quality of life during the year after acute myocardial infarction. Methods: A total of 2600 U.S. and 400 Canadian patients were randomly selected from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial. Base-line data from their initial hospitalizations were analyzed, and the patients were then interviewed by telephone 30 days, 6 months, and 1 year after myocardial infarction to determine their use of medical care and quality of life. Results: The Canadian patients typically stayed in the hospital one day longer (P = 0.009) than the U.S. patients but had a much lower rate of cardiac catheterization (25 percent vs. 72 percent, P<0.001), coronary angioplasty (11 percent vs. 29 percent, P<0.001), and coronary bypass surgery (3 percent vs. 14 percent, P<0.001). At one year 24 percent of the Canadian and 53 percent of the U.S. patients had undergone angioplasty or bypass surgery at least once (P<0.001). The Canadians had more visits to physicians during the follow-up year (P<0.001), but fewer visits to specialists (P<0.001). At 30 days, functional status was equivalent in the patients from the two countries. However, after one year the U.S. patients had substantially more improvement than the Canadian patients (P<0.001). The prevalence of chest pain and dyspnea at one year was higher among the Canadian patients (34 percent vs. 21 percent and 45 percent vs. 29 percent, respectively; P<0.001). Conclusions: The Canadian patients had more cardiac symptoms and worse functional status one year after acute myocardial infarction than the U.S. patients. The Canadian patients also underwent fewer invasive cardiac procedures and had fewer visits to specialist physicians. These results suggest, but do not prove, that the more aggressive pattern of care in the United States may have been responsible for the better quality of life. (N Engl J Med 1994;331:1130-5.) [ABSTRACT FROM AUTHOR]

Background: For patients hospitalized for heart failure with reduced ejection fraction (HFrEF), guidelines recommend optimization of medical therapy prior to discharge. The degree to which changes in medical therapy occur during hospitalizations for HFrEF in North American clinical practice is unclear., Methods: The VICTORIA registry (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) enrolled patients hospitalized for worsening chronic HFrEF across 51 sites in the United States and Canada from February 2018-January 2019. In patients with complete medication data who were not receiving dialysis, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor neprilysin inhibitor (ARNI), beta-blocker, mineralocorticoid receptor antagonist (MRA), and sodium glucose cotransporter-2 inhibitors (SGLT2i) were assessed at admission and discharge., Results: Of 1695 patients, the median (IQR) age was 69 (59-79) years, and 33% were women. Among eligible patients, 33%, 25% and 55% were not prescribed ACEI/ARB/ARNI, beta-blocker, and MRA at discharge, respectively; 99% were not prescribed SGLT2i. For each medication, > 50% of patients remained on stable subtarget doses or no medication during hospitalization. In-hospital rates of initiation/dose increase were 20% for ACEI/ARB, 4% for ARNI, 20% for beta-blocker, 22% for MRA, and < 1% for SGLT2i; corresponding rates of dose decrease/discontinuation were 11%, 2%, 9%, 5%, and < 1%, respectively. Overall, 17% and 28% of eligible patients were prescribed triple therapy prior to admission and at discharge, respectively. At both admission and discharge, 1% of patients were prescribed triple therapy at target doses. Across classes of medication, multiple factors were independently associated with higher likelihood of in-hospital initiation/dosing increase (eg, Canadian enrollment, white race, admission to intensive care units) and discontinuation/dosing decrease (eg, worse renal function, admission to intensive care units)., Conclusions: In this contemporary North American registry of patients hospitalized for worsening chronic HFrEF, for each recommended medical therapy, the large majority of eligible patients remained on stable subtarget doses or without medication at admission and discharge. Although most patients had no alterations in medical therapy, hospitalization in Canada and multiple patient characteristics were associated with higher likelihood of favorable in-hospital medication changes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Randomized controlled trials (RCTs) often target enrollment of patients with demographics and outcomes less representative of the broader population of interest. To provide context for the VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction), we designed a registry of hospitalized patients with worsening heart failure to characterize their clinical profile, outcomes, and reasons for their nonparticipation in a RCT., Methods: Fifty-one RCT sites in Canada and the United States participated. Eligible patients included those with chronic heart failure, hospitalized for heart failure, and an ejection fraction <45%; no other exclusions were applied. Sites identified patients between 2017 and 2019 during the RCT enrollment period. RCT eligibility criteria were applied, and non-mutually exclusive reasons for nonenrollment were captured. Mortality at 1 year was estimated via the Meta-Analysis Global Group in Chronic Heart Failure risk score or as observed in the RCT., Results: Overall, 2056 patients were enrolled in the registry; 61% (n=1256) were ineligible for the RCT, 37% (n=766) were eligible but not enrolled, and 2% (n=34) were also enrolled in the RCT. Registry participants had a median age of 70, 33% were women, and 63% were White. The median risk score predicted a 20.9% 1-year mortality, higher than in the RCT (predicted 14.7% and observed 11.5%). Major reasons for ineligibility in the RCT included the use of nitrates (23%), systolic blood pressure <100 mm Hg (12%), and substance use (11%) with other exclusion criteria <10%. For eligible patients, reasons for nonparticipation in the RCT included lack of interest in participating (28%), poor compliance (25%), inability to complete follow-up (23%), too sick (20%), unable to provide consent (17%), and distance from site (15%)., Conclusions: Patients with worsening heart failure in routine clinical practice exhibit high-risk features, and approximately one-third were eligible for an RCT but excluded. The majority of these nonparticipating patients had modifiable reasons. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02861534.

Background: Length of stay after non-ST-segment elevation myocardial infarction (NSTEMI) continues to decrease, but information to guide duration of hospitalization is limited., Methods: We used landmark analyses, in which the landmark defined potential days of discharge, to estimate complication rates on the first day the patient would have been out of the hospital, and estimated associations between timing of discharge and 30-day and 1-year event-free survival after discharge among NSTEMI patients., Results: Among 20,410 NSTEMI patients, median length of stay was 7 (4, 12) days; 3,209 (15.7%) experienced a cardiac complication on days 0 to 2 and 1,322 (6.5%) were discharged without complications during hospital days 0 to 2. At the start of day 3, 15,879 patients (77.8%) were still hospitalized without complications. Of these, 1,689 (10.6%) were discharged event-free on day 3. Adjusted event-free survival rates of death or myocardial infarction from day 4 to 30 days after among the 1,689 patients was 99.1% compared with 93.1% for the 14,190 who remained hospitalized at the end of day 3. For 1-year mortality, these rates were 98.1% and 96.4%, respectively. Among 13,334 patients hospitalized without complications at the start of day 4, 1,706 were discharged event-free that day. Adjusted survival rates among these patients, compared with those still hospitalized at the end of day 4, were 98.0% versus 93.7% for 30-day death or myocardial infarction and 97.8% versus 96.1% for 1-year mortality., Conclusions: Patients with NSTEMI who had no serious complications during the first 2 hospital days were at low risk of subsequent short- and intermediate-term death or ischemic events., (Copyright © 2018. Published by Elsevier Inc.)

Aims: The incidence of and factors associated with sudden cardiac death (SCD) early after an acute heart failure (HF) hospital admission have not been well defined., Methods and Results: We assessed SCD and ventricular arrhythmias in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, which included patients with acute HF with reduced or preserved ejection fraction. SCD, resuscitated SCD (RSCD), and sustained ventricular tachycardia/ventricular fibrillation (VT/VF) were adjudicated from randomization through 30 days and were combined into a composite endpoint. Baseline characteristics associated with this composite were determined by logistic regression. RSCD and VT/VF were included as time-dependent variables in a Cox model evaluating the association of these variables with 180-day all-cause mortality. Among 7011 patients, the 30-day all-cause mortality rate was 3.8%; SCD accounted for 17% of these deaths. The 30-day composite event rate was 1.8% (n = 121). Ten patients had more than one event with 30-day Kaplan-Meier event rates of 0.6% for SCD [95% confidence interval (CI) 0.5%-0.9%, n = 43], 0.4% for RSCD (95% CI 0.2%-0.5%, n = 24), and 0.9% for VT/VF (95% CI 0.7%-1.2%, n = 64). In the multivariable model, chronic obstructive pulmonary disease, history of VT, male sex, and longer QRS duration were associated with SCD, RSCD, or VT/VF. A RSCD or VT/VF event was associated with higher 180-day mortality (adjusted hazard ratio 6.6, 95% CI 4.8-9.1, P < 0.0001)., Conclusions: Approximately 2% of patients admitted for acute HF experienced SCD, RSCD, or VT/VF within 30 days of admission, and SCD accounted for 17% of all deaths within 30 days., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Unlabelled: Non-ST-segment myocardial infarction (NSTEMI) can be complicated by high-degree atrioventricular (AV) block, asystole, or electromechanical dissociation (EMD), but these events are not well characterized in the contemporary era. This analysis assesses the incidence of and factors associated with these dysrhythmias in acute NSTEMIs., Methods: Patients with NSTEMI in the EARLY ACS, PLATO, and TRACER trials were included in the pooled cohort (N = 29,677). Logistic regression was used to identify factors associated with in-hospital high-degree AV block and asystole or EMD, and Kaplan-Meier methods were used to assess mortality., Results: High-degree AV block occurred in 112 (0.4%) patients, asystole in 157 (0.5%), and EMD in 38 (0.1%). Pacemakers were inserted in 241 patients (0.8%) during the index hospitalization: 30 (12%) for AV block. Among patients with high-degree AV block, we observed more frequent right coronary artery lesions (47% vs 29%). Age, diabetes, lower heart rate, and lower blood pressure were associated with high-degree AV block. Higher Killip class, ST-segment depression, prior myocardial infarction, and peripheral vascular disease were most strongly associated with asystole or EMD. Ten-day unadjusted survival was 90% for patients with high-degree AV block and 43% for those with asystole or EMD., Conclusions: Although high-degree AV block, asystole, and EMD were infrequent complications of NSTEMI, they were associated with substantial short-term mortality. Only 1 in 8 pacemakers placed in NSTEMI patients during the acute hospitalization was for high-degree AV block., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Patients hospitalized for acute decompensated heart failure (ADHF) are at high risk for early mortality and rehospitalization. Risk stratification of ADHF using clinically available data on admission is increasingly important to integrate with clinical pathways. Our goal was to create a simple method of screening patients upon admission to identify those with increased risk of future adverse events., Methods: Using ASCEND-HF, a pragmatic clinical trial conducted in 398 sites globally, we developed and validated logistic regression risk models for (a) 30-day mortality/HF rehospitalization, (b) 30-day mortality/all-cause rehospitalization, (c) 30-day all-cause mortality, and (d) 180-day all-cause mortality. Fifty-one candidate variables were evaluated based on prior publications and clinical review. Final models were selected based on stepwise selection with entry and a staying criterion of P < .01. The 30-day mortality model was externally validated, and coefficients were converted to an additive risk score., Results: Among 7,141 patients, the median age was 67 years, 34% were female, and 80% had a left ventricular ejection fraction <40%. The models had between 5 and 12 risk factors with c-indices ranging from 0.68 to 0.75. A simplified score, including age, systolic blood pressure, sodium, blood urea nitrogen, and dyspnea at rest, discriminated 30-day mortality risk from 0.5% (score 0) to 53% (score 10)., Conclusions: Commonly available clinical variables provide simple risk stratification for clinical outcomes among patients with ADHF, and these models may be considered for integration into routine clinical care., (Copyright © 2015. Published by Elsevier Inc.)

Background: Adequate representation by sex in trials allows generalizability of results. We examined representation of women in clinical trials during a 17-year period in which inclusion criteria were broadened and federal mandates for representativeness were launched., Methods and Results: Using mixed models, we studied sex-stratified temporal trends in enrollment, clinical characteristics, treatment, and outcomes among 76 148 non-ST-segment elevation acute coronary syndrome patients using patient-level data merged from 11 phase III trials conducted from 1994 to 2010. Overall, 33.3% of patients were women, which changed minimally over time. Women were consistently 4 to 5 years older than men (median age 68 [interquartile range 61-75] versus 64 [interquartile range 56-72] years) and more frequently had diabetes mellitus, hypertension, and heart failure; men more frequently had prior myocardial infarction and revascularization. GRACE risk scores increased over time for both sexes with the inclusion of older patients with more comorbidities. Use of percutaneous coronary intervention, in-hospital and discharge angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, β-blockers, and lipid-lowering drugs also increased among both sexes. Kaplan-Meier estimates of 6-month mortality declined from 7.0% [95% confidence interval 6.5%-7.6%] to 4.5% [95% confidence interval 4.0%-5.0%] among women and 6.3% [95% confidence interval 6.0%-6.7%] to 3.1% [95% confidence interval 2.9%-3.4%] among men during the 17-year period., Conclusions: The relative proportion of women in non-ST-segment elevation acute coronary syndrome trials changed minimally over time. Nevertheless, in parallel with men, use of evidence-based care and outcomes improved significantly over time among women., (© 2015 American Heart Association, Inc.)

Despite the global burden of cardiovascular disease, investment in cardiovascular drug development has stagnated over the past 2 decades, with relative underinvestment compared with other therapeutic areas. The reasons for this trend are multifactorial, but of primary concern is the high cost of conducting cardiovascular outcome trials in the current regulatory environment that demands a direct assessment of risks and benefits, using clinically-evident cardiovascular endpoints. To work toward consensus on improving the environment for cardiovascular drug development, stakeholders from academia, industry, regulatory bodies, and government agencies convened for a think tank meeting in July 2014 in Washington, DC. This paper summarizes the proceedings of the meeting and aims to delineate the current adverse trends in cardiovascular drug development, understand the key issues that underlie these trends within the context of a recognized need for a rigorous regulatory review process, and provide potential solutions to the problems identified., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Peak creatine kinase (CK)-MB concentration is related to reperfusion success and clinical outcomes after fibrinolytic therapy for acute myocardial infarction. However, prognostic implications of CK-MB measurements after primary percutaneous coronary intervention (PCI), which provides more predictable and consistent reperfusion, are unknown., Methods: We pooled 2,042 primary PCI-treated ST-segment elevation myocardial infarction (STEMI) patients from 3 trials with serial core laboratory-determined CK-MB measurements; 1,799 patients (88.1%) who survived to 36 hours and had ≥4 CK-MB measurements were studied. Cox regression modeling was performed to quantify the association between peak CK-MB concentration (and area under the time-concentration curve [AUC]) and mortality at 6 months, and death or congestive heart failure at 90 days., Results: The median (25th-75th percentiles) peak CK-MB concentration and AUC measurement through 36 hours were 239 (109-429) ng/mL and 4,263 (2,081-7,124) ng/(mL h), respectively. By multivariable analysis, peak CK-MB concentration and AUC measurement were independently associated with 6-month mortality (adjusted hazard ratio [HR] 1.15, 95% CI 1.05-1.25, per 100-ng/mL increase, P = .002; and adjusted HR 1.09, 95% CI 1.03-1.14, per 1,000-ng/[mL h] increase, P < .001, respectively) and 90-day death or congestive heart failure (adjusted HR 1.26, 95% CI 1.18-1.34, P < .001; and adjusted HR 1.15, 95% CI 1.11-1.19, P < .001, respectively)., Conclusions: Peak CK-MB concentration and AUC measurement are independent predictors of 3- to 6-month cardiovascular outcomes in primary PCI-treated STEMI patients. Our findings guide application of these measurements as efficacy end points in early-phase studies evaluating new therapies for STEMI., (Copyright © 2014 Mosby, Inc. All rights reserved.)

The therapeutic potential of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (PCI) is unknown. This prespecified analysis of a postrandomization subgroup evaluated the effects of vorapaxar compared with placebo among Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) participants undergoing PCI, focusing on the implanted stent type (drug-eluting stent [DES] vs bare-metal stent [BMS]). Among 12,944 recruited patients, 7,479 (57.8%) underwent PCI during index hospitalization, and 3,060 (40.9%) of those patients received exclusively BMS, whereas 4,015 (53.7%) received DES. The median (twenty-fifth, seventy-fifth percentiles) duration of thienopyridine therapy was 133 days (47, 246) with BMS and 221 days (88, 341) with DES. At 2 years among patients undergoing PCI, the primary (cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) and secondary (cardiovascular death, myocardial infarction, or stroke) end points did not differ between vorapaxar and placebo groups, which was consistent with the treatment effect observed in the overall study population (p value for interaction = 0.540). However, the treatment effect trended greater (p value for interaction = 0.069) and the risk for bleeding in patients taking vorapaxar versus placebo appeared attenuated in BMS-only recipients. After adjustment for confounders, the interaction was no longer significant (p value = 0.301). The covariate that mostly explained the stent-type-by-treatment interaction was the duration of clopidogrel therapy. In conclusion, among patients with PCI, the effect of vorapaxar is consistent with the overall TRACER results. Patients who received a BMS underwent shorter courses of clopidogrel therapy and displayed trends toward greater ischemic benefit from vorapaxar and lesser bleeding risk, compared with patients who received a DES., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) initiated after myocardial infarction (MI) reduce mortality and are American College of Cardiology/American Heart Association guideline recommended. Yet the extent to which ACEI/ARB therapy is applied in patients with acute coronary syndrome at hospital discharge is unclear., Methods and Results: We performed an observational analysis of 80 241 patients admitted with an acute coronary syndrome and discharged home from 311 U.S. hospitals participating in the Get With the Guidelines-Coronary Artery Disease Program from January 2005 to December 2009. Among the 60,847 patients with an American College of Cardiology/American Heart Association class I indication (left ventricular dysfunction or medical history of heart failure, hypertension, diabetes mellitus, or chronic kidney disease), 49,682 (81.7%) received ACEI/ARB with an increase in the rate of treatment over the study period (76.7%-84.6%; adjusted odds ratio, 1.17; 95% confidence interval, 1.10-1.24; P<0.001, per calendar year). In-hospital coronary artery bypass grafting and renal insufficiency were independently associated with lower use (adjusted odds ratio, 0.55; 95% confidence interval, 0.48-0.63 and adjusted odds ratio, 0.58; 95% confidence interval, 0.52-0.64, respectively)., Conclusions: Results from this large U.S. national registry suggest that 1 in 5 eligible patients hospitalized for acute coronary syndrome failed to receive American College of Cardiology/American Heart Association class I guideline-recommended ACEI/ARB therapy, and the use varies by patient factors. In particular, the low likelihood of ACEI/ARB after coronary artery bypass grafting surgery or in patients with renal insufficiency raises concern. These findings highlight an unmet need in this population and provide an incentive for additional quality improvement efforts.

Objectives: To assess whether systemic inflammatory response syndrome is associated with morbidity and mortality in ST-elevation myocardial infarction., Design and Setting: Secondary analysis of multicenter randomized controlled trials., Patients: Complement and reduction of infarct size after angioplasty or lytics project patients (n=1,903) with ST-elevation myocardial infarction undergoing fibrinolysis or mechanical reperfusion., Interventions: None., Measurements and Main Results: The prevalence of systemic inflammatory response syndrome was described in the 1,186 patients (64.4%) with data available for all systemic inflammatory response syndrome criteria. Using multiple imputations for the 1,843 patients (96.8%) with available endpoints, we compared the 90-day prevalence of death, shock, heart failure, or stroke between patients with and without systemic inflammatory response syndrome at presentation and at 24 hours post admission. Systemic inflammatory response syndrome was defined as ≥2 of 1) heart rate>90 beats/min, 2) respiratory rate>20 breaths/min, 3) body temperature>38 or <36°C, or 4) leukocyte count>12 or<4×10/L. At presentation, 25.0% of patients met systemic inflammatory response syndrome criteria; at 24 hours, 8.1% of patients met systemic inflammatory response syndrome criteria. The primary outcome was more frequent among patients with systemic inflammatory response syndrome at presentation (31.0% vs 16.7%; adjusted hazard ratio, 1.78 [95% CI, 1.35-2.34]; p<0.001) and at 24 hours (36.7% vs 11.1%; adjusted hazard ratio, 2.84 [95% CI, 2.03-3.97]; p<0.001). Mortality at 90 days was also higher among patients with systemic inflammatory response syndrome at either time point. Each additional systemic inflammatory response syndrome criterion was independently associated with 90-day outcomes at the time of presentation (adjusted hazard ratio, 1.41 per systemic inflammatory response syndrome criteria [95% CI, 1.24-1.61]; p<0.001) and at 24 hours (adjusted hazard ratio, 1.72 per systemic inflammatory response syndrome criteria [95% CI, 1.47-2.01]; p<0.001)., Conclusion: The diagnosis of systemic inflammatory response syndrome and the cumulative number of systemic inflammatory response syndrome criteria were independently associated with 90-day clinical outcomes in a population of patients with ST-elevation myocardial infarction. The independent association of this simple composite measure of the inflammatory response with outcomes underscores the importance of the clinical inflammatory response in ST-elevation myocardial infarction.

Background: Hospital readmission is an important clinical outcome of patients with heart failure. Its relation to length of stay for the initial hospitalization is not clear., Methods and Results: We used hierarchical modeling of data from a clinical trial to examine variations in length of stay across countries and across hospitals in the United States and its association with readmission within 30 days of randomization. Main outcomes included associations between country-level length of stay and readmission rates, after adjustment for patient-level case mix; and associations between length of stay and readmission rates across sites in the United States. Across 27 countries with 389 sites and 6848 patients, mean length of stay ranged from 4.9 to 14.6 days (6.1 days in the United States). Rates of all-cause readmission ranged from 2.5% to 25.0% (17.8% in the United States). There was an inverse correlation between country-level mean length of stay and readmission (r=-0.52; P<0.01). After multivariable adjustment, each additional inpatient day across countries was associated with significantly lower risk of all-cause readmission (odds ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.02) and heart failure readmission (odds ratio, 0.79; 95% confidence interval, 0.69-0.99; P=0.03). Similar trends were observed across US study sites concerning readmission for any cause (odds ratio, 0.92; 95% confidence interval, 0.85-1.00; P=0.06) and readmission for heart failure (odds ratio, 0.90; 95% confidence interval, 0.80-1.01; P=0.07). Across countries and across US sites, longer median length of stay was independently associated with lower risk of readmission., Conclusions: Countries with longer length of stay for heart failure hospitalizations had significantly lower rates of readmission within 30 days of randomization. These findings may have implications for developing strategies to prevent readmission, defining quality measures, and designing clinical trials in acute heart failure., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852.

Objectives: The aim of this study was to address the knowledge gap using the APEX-AMI (Assessment of Pexelizumab in Acute Myocardial Infarction) trial database. We also assessed the association between serious infections and 90-day death or death/myocardial infarction (MI)., Background: Little is known about the incidence, location, etiological organisms, and outcomes of infection in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention., Methods: We analyzed data from 5,745 STEMI patients enrolled in the APEX-AMI trial. Detailed information on infection was collected for all patients. We described characteristics of patients according to infection and details of infection. Cox proportional hazards models were used to assess 90-day outcomes among patients with and without infections after adjusting for associated clinical variables and with infection as a time-dependent covariate., Results: Overall, 138 patients developed a serious infection (2.4%), most of whom presented with a single-site infection. The median (25th, 75th percentile) time until diagnosis of infection was 3 (1, 6) days. The most commonly identified organism was Staphylococcus aureus, and the main location of infection was the bloodstream. These patients had more comorbidities and lower procedural success at index percutaneous coronary intervention than those without infections. Serious infection was associated with significantly higher rates of 90-day death (adjusted hazard ratio: 5.6; 95% confidence interval: 3.8 to 8.4) and death or MI (adjusted hazard ratio: 4.9; 95% confidence interval: 3.4 to 7.1)., Conclusions: Infections complicating the course of patients with STEMI were uncommon but associated with markedly worse 90-day clinical outcomes. Mechanisms for early identification of these high-risk patients as well as design of strategies to reduce their risk of infection are warranted., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Despite advances in therapy, global mortality due to acute myocardial infarction remains high. The international Hirulog and Early Reperfusion or Occlusion (HERO-2) trial of 17,073 patients with ST-segment elevation myocardial infarction provided the opportunity to explore international differences in outcomes., Methods: Patient characteristics, treatment, and outcomes were compared across 5 diverse regions: Western countries, Latin America, Eastern Europe, Russia, and Asia. In addition, a representative sample of 1,743 screened patients was compared with enrolled patients., Results: Larger percentages of eligible patients were randomized in Eastern Europe, Russia, and Asia than Western countries. These regions enrolled more patients with anterior myocardial infarction, Killip class III or IV, and late presentation (>4 hours). More patients aged >75 years were enrolled from Western countries. Overall risk levels were similar. Eastern Europe and Russia had lower rates than Western countries of coronary revascularization (2% vs 18%) and longer hospital stays (median 18 vs 7 days). Thirty-day mortality was lower in Western countries; 6.7% versus 10.2% to 13.2% elsewhere, whereas reinfarction was more frequent (3.2% vs 1.5% to 3.0%; each, P < .001). Regional mortality differences persisted after adjustment for baseline risk factors, treatments, or national health and economic statistics (each P < .001)., Conclusions: The variation in mortality and other clinical outcomes across geographic regions was not adequately explained by risk factors, patterns of care, or national health statistics. Nevertheless, large international trials are a better way to assess potential new treatments across many countries than the alternative of separate smaller trials in each region., (Copyright 2010 Mosby, Inc. All rights reserved.)

The Assessment of the Safety and Efficacy of a New Thrombolytic 3 (ASSENT 3 PLUS) Plus trial (n=1639) was an international trial of pre-hospital fibrinolysis with tenecteplase randomly assigned to enoxaparin or unfractionated heparin, involving 106 sites in 12 countries. Given the potential impact of process of care delivery in various healthcare systems, we undertook a comprehensive validated survey of population demographics, geographical factors, emergency medical services, methods of electrocardiogram interpretation and pre-hospital fibrinolysis administration. The potential study population was 42.4 x 10(6) with 70% urban. The land areas of individual emergency medical services sites varied from 6 to 20000/km(2). Three emergency medical services personnel (range 2-5) attended each ambulance with the highest level of training, consisting of a physician (65%), registered nurse (20%) or paramedic. Before the initiation of the study, 72% of sites administered pre-hospital fibrinolysis (range 1-20 years). Electrocardiograms were interpreted on the scene in 60% and transmitted for physician's interpretation in the remainder; 41% of patients (679/1639) were enrolled at sites without a physician at the scene. The ASSENT 3 Plus trial incorporated a wide variation in population density, emergency medical services resources, and physician's interpretation of ECG and administering pre-hospital fibrinolysis. Understanding this diversity will help in evaluating the general applicability and feasibility of pre-hospital fibrinolysis in various health systems, as well as the pre-hospital care of ST elevation myocardial infarction patients regardless of reperfusion strategies.

Background: Comparing American and Canadian practice patterns and outcomes offers a natural experiment to examine the relative benefits of aggressive versus conservative management of coronary artery disease. In a prospective substudy of the Global Use of Strategies to Open Occluded Coronary Arteries IIb (GUSTO-IIb) trial, differences in the management of non-ST elevation acute coronary syndrome, and the associated impact on quality of life (QOL) outcomes, were examined in the two countries., Methods and Results: The patient population, selected randomly from the parent trial population, comprised 390 Canadian and 1122 American patients for whom both baseline and one-year data were available. Validated instruments were used to assess QOL, including the Duke Activity Status Index (DASI) and scales from the SF-36 questionnaire. At baseline, American patients had significantly higher cardiac catheterization rates (83% versus 45%), percutaneous coronary intervention rates (39% versus 24%) and coronary bypass surgery rates (19% versus 12%) than did Canadian patients, respectively. However, at one year, Canadian coronary bypass surgery rates were at par with those in the United States (24% versus 26%, respectively). At baseline, the mean DASI score was 24.6 among Canadian patients and 23.4 among American patients (P=0.14). At one year, neither cohort reported any significant change in functional scores and there was no intercountry difference in DASI scores, even after accounting for baseline risk. Canadian patients had significantly worse mental health scores than American patients at baseline (mean score 71.6 versus 75.4, respectively; P=0.02), but by one year, Canadian patients had better scores (mean score 80.1 versus 76.2, respectively; P=0.01). After adjusting for baseline characteristics, Canadian patients continued to report better mental health status scores than did American patients (4 points higher, P<0.01). When asked to rate their health state on a scale from 0 to 100, both cohorts reported similar values at baseline. However, after adjusting for baseline characteristics, American patients' perception of their health state was better than that reported by Canadians (3 points higher, P<0.01)., Conclusion: Despite higher rates of invasive procedures in the American cohort, one-year QOL outcomes in the cohort were similar to those in the more conservatively managed Canadian cohort. These results suggest that routine cardiac catheterization and increased procedure use may be associated with diminishing marginal returns with respect to improving QOL outcomes among patients with non-ST elevation acute coronary syndromes.

Background: Early discharge of low-risk patients with acute myocardial infarction is feasible and can be achieved at no additional risk of adverse events. We aimed to identify the extent to which countries have taken advantage of the opportunity for early discharge., Methods: The study population consisted of 54174 patients enrolled in GUSTO-I, GUSTO-III, and ASSENT-2 studies (enrollment period 1990-98) in the USA, Canada, Australia, New Zealand, Belgium, France, Germany, Spain, and Poland. We identified patients with uncomplicated acute myocardial infarction who were eligible for early discharge on the basis of previously established criteria, and assessed the extent to which these patients were discharged early--defined as discharged alive within 4 days of admission. The economic consequences (defined as potentially unnecessary hospital days consumed per 100 patients enrolled) were also investigated., Findings: Patients in all European countries had significantly longer stays than did those from non-European countries. Over the study period, the number of eligible patients discharged on or before day 4 increased in the USA, Canada, Australia, and New Zealand. Despite this increase, no more than 40% of patients who were eligible for early discharge were actually discharged early. The rate of early discharge of eligible patients was consistently low (<2%) in Belgium, France, Germany, Spain, and Poland. In ASSENT-2, which is the most recent trial in this study, the number of potentially unnecessary hospital days (per 100 patients enrolled) ranged from 65 in New Zealand to 839 in Germany., Interpretation: Despite more than a decade of research, there is still a lot of variation between countries in international length-of-stay patterns in acute myocardial infarction. The potential for more efficient discharge of low-risk patients exists in all countries investigated, but was especially evident in the European countries included in the study (Belgium, France, Germany, Spain, and Poland).

Objectives: To investigate the impact of on-site cardiac interventional facilities on the management and outcome of patients with versus those without ST elevation acute coronary syndromes (ACS) in the Canadian-American Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb population., Methods: Data from 4605 patients were analyzed in relation to the admitting hospital's capability to perform coronary procedures (noninvasive, angiography-capable and interventional hospitals). Differences in medication use, revascularization rate and patient outcome were determined., Results: Whereas medication use during hospitalization and at discharge differed between non-ST elevation ACS patients treated in the three groups, these were generally more comparable among ST elevation ACS patients. In both ST segment cohorts, patients treated in interventional hospitals underwent coronary procedures more often (angiography rate greater than 70% versus 40% for noninvasive hospitals) and sooner (median two to three days versus four days in noninvasive hospitals) than those treated in other hospitals. Recurrent ischemia was significantly less common in non-ST elevation ACS patients treated in interventional hospitals (32% versus 36% in angiography-capable and 40% in noninvasive hospitals, P<0.001) and tended to be less common among ST elevation ACS patients treated in interventional hospitals. Patients treated in interventional hospitals tended to have lower mortality in the non-ST elevation ACS cohort but significantly fewer died in the ST elevation ACS during hospitalization and at 30 days, six months and one year (8.8% versus 11% in angiography-capable and 15% in noninvasive hospitals, P=0.015). These differences in mortality persisted after adjustment for key baseline covariates. Separate analysis of Canadian and American patients revealed similar mortality patterns, as to the total population, in both ST segment cohorts., Conclusions: Presence of an on-site cardiac interventional facility favourably affected the management and outcome of ACS patients in both non-ST and ST elevation cohorts.

Background: Improved patient selection may optimize the efficiency of cardiac catheterization in both high- and low-rate regions. The purpose of this study was to develop and validate a clinical model for predicting high-risk coronary artery disease (CAD) after myocardial infarction (MI) and to examine the model's potential impact on the use rate of both US and Canadian catheterization practices., Methods and Results: By the use of baseline clinical variables from 1122 patients in the angiographic substudy of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-1) trial, we developed a model that was predictive of severe CAD (left main or triple-vessel disease). The final model, which included prior MI, age, sex, hyperlipidemia, and decreased left ventricular ejection fraction (C-index = 0.70), was externally validated in 781 patients in the GUSTO IIb trial. Although the probability of severe CAD predicted 5-year survival, the frequency of catheterization in both Canada and the United States bore no relationship to severe CAD risk in the GUSTO-1 trial. By use of the model, we estimated that as much as 15% of US catheterizations from both GUSTO-1 and GUSTO IIb might have been avoided, without significantly compromising the number of patients with severe CAD who were identified (sensitivity = 0.94). By applying the model to Canadian practices, an additional 30 cases of severe CAD might have been identified per every 1000 catheterizations performed, without increasing the catheterization rate., Conclusions: The likelihood of severe CAD after ST-elevation MI may be predicted from simple baseline clinical variables. The use of a severe CAD predictive model to guide patient selection might enhance the cost-effectiveness of both aggressive and conservative catheterization practices.

Study Objective: Early treatment with fibrinolytic therapy substantially decreases mortality in acute myocardial infarction (AMI). We examined delays to hospital arrival and treatment in 2 large, multinational, randomized trials of fibrinolytic therapy: Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III)., Methods: We evaluated delays to hospital arrival, time from arrival to treatment, and total time to treatment in the 27,849 US patients with AMI enrolled in GUSTO-I or GUSTO-III. Time intervals were defined prospectively for total time to treatment and symptom onset to hospital arrival as 0 to 2 hours (early), 2 to 4 hours, or more than 4 hours (late). Time to fibrinolytic therapy once in hospital was prospectively defined as 0 to 1 hour (early) or more than 1 hour (late). Socioeconomic data were also obtained from patients enrolled in the GUSTO-III trial., Results: In GUSTO-III, as in GUSTO-I, patients who arrived at the hospital later were older (64 years versus 60 years; P =.001) and more often female (35% versus 27%; P =.001), black (6% versus 4%; P =.02), and diabetic (25% versus 16%; P =.001). These groups also received treatment later once in hospital, as did patients with hypertension (48% versus 42%; P =.001), previous angina (46% versus 36%; P =.001), and previous infarction (21% versus 16%; P =.001). Higher levels of education, professional occupations, and private health insurance were associated with significantly earlier arrival and treatment. Although in hospital time to treatment has decreased (66 minutes to 48 minutes; P <.0001), time to arrival has not changed over the past 7 years, averaging 84 minutes., Conclusion: Certain groups of patients with AMI, including the elderly, women, diabetic patients, and minorities, exhibit delays to hospital arrival and treatment in the emergency setting. Patients with higher educational levels, professional occupations, and private health insurance arrive at the hospital sooner and receive treatment more quickly. Patients and health care providers must be educated regarding high-risk populations for delay to maximize benefit from fibrinolytic therapy.