Cardiovascular outcome trials in patients with chronic kidney disease: challenges associated with selection of patients and endpoints.

Although cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis. Several factors contribute to both the paucity of trials and the apparent lack of observed treatment effect in completed studies. Challenges associated with conducting trials in this population include patient heterogeneity, complexity of renal pathophysiology and its interaction with cardiovascular disease, and competing risks for death. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), an international organization of academic cardiovascular and renal clinical trialists, held a meeting of regulators and experts in nephrology, cardiology, and clinical trial methodology. The group identified several research priorities, summarized in this paper, that should be pursued to advance the field towards achieving improved cardiovascular outcomes for these patients. Cardiovascular and renal clinical trialists must partner to address the uncertainties in the field through collaborative research and design clinical trials that reflect the specific needs of the chronic and end-stage kidney disease populations, with the shared goal of generating robust evidence to guide the management of cardiovascular disease in patients with kidney disease.

Early diagnosis of acute coronary syndrome.

The diagnostic evaluation of acute chest pain has been augmented in recent years by advances in the sensitivity and precision of cardiac troponin assays, new biomarkers, improvements in imaging modalities, and release of new clinical decision algorithms. This progress has enabled physicians to diagnose or rule-out acute myocardial infarction earlier after the initial patient presentation, usually in emergency department settings, which may facilitate prompt initiation of evidence-based treatments, investigation of alternative diagnoses for chest pain, or discharge, and permit better utilization of healthcare resources. A non-trivial proportion of patients fall in an indeterminate category according to rule-out algorithms, and minimal evidence-based guidance exists for the optimal evaluation, monitoring, and treatment of these patients. The Cardiovascular Round Table of the ESC proposes approaches for the optimal application of early strategies in clinical practice to improve patient care following the review of recent advances in the early diagnosis of acute coronary syndrome. The following specific 'indeterminate' patient categories were considered: (i) patients with symptoms and high-sensitivity cardiac troponin <99th percentile; (ii) patients with symptoms and high-sensitivity troponin <99th percentile but above the limit of detection; (iii) patients with symptoms and high-sensitivity troponin >99th percentile but without dynamic change; and (iv) patients with symptoms and high-sensitivity troponin >99th percentile and dynamic change but without coronary plaque rupture/erosion/dissection. Definitive evidence is currently lacking to manage these patients whose early diagnosis is 'indeterminate' and these areas of uncertainty should be assigned a high priority for research.

Improving public health by improving clinical trial guidelines and their application.

Evidence generated from randomized controlled trials forms the foundation of cardiovascular therapeutics and has led to the adoption of numerous drugs and devices that prolong survival and reduce morbidity, as well as the avoidance of interventions that have been shown to be ineffective or even unsafe. Many aspects of cardiovascular research have evolved considerably since the first randomized trials in cardiology were conducted. In order to be large enough to provide reliable evidence about effects on major outcomes, cardiovascular trials may now involve thousands of patients recruited from hundreds of clinical sites in many different countries. Costly infrastructure has developed to meet the increasingly complex organizational and operational requirements of these clinical trials. Concerns have been raised that this approach is unsustainable, inhibiting the reliable evaluation of new and existing treatments, to the detriment of patient care. These issues were considered by patients, regulators, funders, and trialists at a meeting of the European Society of Cardiology Cardiovascular Roundtable in October 2015. This paper summarizes the key insights and discussions from the workshop, highlights subsequent progress, and identifies next steps to produce meaningful change in the conduct of cardiovascular clinical research.

Emergency management of severe hyperkalemia: Guideline for best practice and opportunities for the future.

Hyperkalemia is a common electrolyte disorder, especially in chronic kidney disease, diabetes mellitus, or heart failure. Hyperkalemia can lead to potentially fatal cardiac dysrhythmias, and it is associated with increased mortality. Determining whether emergency therapy is warranted is largely based on subjective clinical judgment. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT) aimed to evaluate the current knowledge pertaining to the emergency treatment of hyperkalemia. The INI-CRCT developed a treatment algorithm reflecting expert opinion of best practices in the context of current evidence, identified gaps in knowledge, and set priorities for future research. We searched PubMed (to August 4, 2015) for consensus guidelines, reviews, randomized clinical trials, and observational studies, limited to English language but not by publication date. Treatment approaches are based on small studies, anecdotal experience, and traditional practice patterns. The safety and real-world effectiveness of standard therapies remain unproven. Prospective research is needed and should include studies to better characterize the population, define the serum potassium thresholds where life-threatening arrhythmias are imminent, assess the potassium and electrocardiogram response to standard interventions. Randomized, controlled trials are needed to test the safety and efficacy of new potassium binders for the emergency treatment of severe hyperkalemia in hemodynamically stable patients. Existing emergency treatments for severe hyperkalemia are not supported by a compelling body of evidence, and they are used inconsistently across institutions, with potentially significant associated side effects. Further research is needed to fill knowledge gaps, and definitive clinical trials are needed to better define optimal management strategies, and ultimately to improve outcomes in these patients.

Heart Failure in Non-Caucasians, Women, and Older Adults: A White Paper on Special Populations From the Heart Failure Society of America Guideline Committee.

The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients.

Advanced (stage D) heart failure: a statement from the Heart Failure Society of America Guidelines Committee.

We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process. Identification of patients in stage D is a clinically important task because treatments are inherently limited, morbidity is typically progressive, and survival is often short. Age, frailty, and psychosocial issues affect both outcomes and selection of therapy for stage D patients. Heart transplant and mechanical circulatory support devices are potential treatment options in select patients. In addition to considering indications, contraindications, clinical status, and comorbidities, treatment selection for stage D patients involves incorporating the patient's wishes for survival versus quality of life, and palliative and hospice care should be integrated into care plans. More research is needed to determine optimal strategies for patient selection and medical decision making, with the ultimate goal of improving clinical and patient centered outcomes in patients with stage D heart failure.

New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes.

The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.

End-of-life care in patients with heart failure.

Stage D heart failure (HF) is associated with poor prognosis, yet little consensus exists on the care of patients with HF approaching the end of life. Treatment options for end-stage HF range from continuation of guideline-directed medical therapy to device interventions and cardiac transplantation. However, patients approaching the end of life may elect to forego therapies or procedures perceived as burdensome, or to deactivate devices that were implanted earlier in the disease course. Although discussing end-of-life issues such as advance directives, palliative care, or hospice can be difficult, such conversations are critical to understanding patient and family expectations and to developing mutually agreed-on goals of care. Because patients with HF are at risk for rapid clinical deterioration or sudden cardiac death, end-of-life issues should be discussed early in the course of management. As patients progress to advanced HF, the need for such discussions increases, especially among patients who have declined, failed, or been deemed to be ineligible for advanced HF therapies. Communication to define goals of care for the individual patient and then to design therapy concordant with these goals is fundamental to patient-centered care. The objectives of this white paper are to highlight key end-of-life considerations in patients with HF, to provide direction for clinicians on strategies for addressing end-of-life issues and providing optimal patient care, and to draw attention to the need for more research focusing on end-of-life care for the HF population.

Acute decompensated heart failure: update on new and emerging evidence and directions for future research.

Acute decompensated heart failure (ADHF) is a complex clinical event associated with excess morbidity and mortality. Managing ADHF patients is challenging because of the lack of effective treatments that both reduce symptoms and improve clinical outcomes. Existing guideline recommendations are largely based on expert opinion, but several recently published trials have yielded important data to inform both current clinical practice and future research directions. New insight has been gained regarding volume management, including dosing strategies for intravenous loop diuretics and the role of ultrafiltration in patients with heart failure and renal dysfunction. Although the largest ADHF trial to date (ASCEND-HF, using nesiritide) was neutral, promising results with other investigational agents have been reported. If these findings are confirmed in phase III trials, novel compounds, such as relaxin, omecamtiv mecarbil, and ularitide, among others, may become therapeutic options. Translation of research findings into quality clinical care can not be overemphasized. Although many gaps in knowledge exist, ongoing studies will address issues around delivery of evidence-based care to achieve the goal of improving the health status and clinical outcomes of patients with ADHF.

Diabetes clinical trials: helped or hindered by the current shift in regulatory requirements?

Glycaemic control is an inadequate surrogate marker of cardiovascular event reduction in patients with type 2 diabetes. Clinical trials to date have been unsuccessful in identifying a therapeutic approach that addresses the underlying problem in diabetes (glycaemic control) and reduces cardiovascular risk. The potential for some agents to increase the risk of cardiovascular events has led to substantial changes in regulatory requirements for new anti-diabetic therapies. These requirements, while key to ensuring the cardiovascular safety of new agents, fail to emphasize the need to show clinical benefits, such as less visual impairment, less need for dialysis, or fewer cardiovascular events and deaths. Changes in test results such as glycaemic control, serum creatinine, micro-albuminuria, or retinopathy are inadequate surrogates. Regulators should consider the potential advantages of offering extended patent protection in order to encourage companies to conduct long-term trials in diabetes and many other chronic medical conditions. Cooperative efforts among physicians, clinical trialists, regulators, and sponsors are needed to address unresolved issues including re-defining therapeutic targets that are meaningful to patients with diabetes, determining the appropriate length of follow-up for future trials, and considering the ethical and operational challenges of non-inferiority designs.

Indications for cardiac resynchronization therapy: 2011 update from the Heart Failure Society of America Guideline Committee.

Cardiac resynchronization therapy (CRT) improves survival, symptoms, quality of life, exercise capacity, and cardiac structure and function in patients with New York Heart Association (NYHA) functional class II or ambulatory class IV heart failure (HF) with wide QRS complex. The totality of evidence supports the use of CRT in patients with less severe HF symptoms. CRT is recommended for patients in sinus rhythm with a widened QRS interval (≥150 ms) not due to right bundle branch block (RBBB) who have severe left ventricular (LV) systolic dysfunction and persistent NYHA functional class II-III symptoms despite optimal medical therapy (strength of evidence A). CRT may be considered for several other patient groups for whom evidence of benefit is clinically significant but less substantial, including patients with a QRS interval of ≥120 to <150 ms and severe LV systolic dysfunction who have persistent mild to severe HF despite optimal medical therapy (strength of evidence B), some patients with atrial fibrillation, and some with ambulatory class IV HF. Several evidence gaps remain that need to be addressed, including the ideal threshold for QRS duration, QRS morphology, lead placement, degree of myocardial scarring, and the modality for evaluating dyssynchrony. Recommendations will evolve over time as additional data emerge from completed and ongoing clinical trials.

Update on aldosterone antagonists use in heart failure with reduced left ventricular ejection fraction. Heart Failure Society of America Guidelines Committee.

Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are guideline-recommended therapy for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk of the primary endpoint of cardiovascular death or HF hospitalization (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.54-0.74, P < .001) and all-cause mortality (adjusted HR 0.76, 95% CI 0.62-0.93, P < .008) after a median of 21 months. Based on EMPHASIS-HF, an MRA is recommended for patients with New York Heart Association (NYHA) Class II-IV symptoms and reduced LVEF (<35%) on standard therapy (Strength of Evidence A). Patients with NYHA Class II symptoms should have another high-risk feature to be consistent with the EMPHASIS-HF population (age >55 years, QRS duration >130 msec [if LVEF between 31% and 35%], HF hospitalization within 6 months or elevated B-type natriuretic peptide level). Renal function and serum potassium should be closely monitored. Dose selection should consider renal function, baseline potassium, and concomitant drug interactions. The efficacy of eplerenone in patients with mild HF symptoms translates into a unique opportunity to reduce morbidity and mortality earlier in the course of the disease.

Improving evidence-based care for heart failure in outpatient cardiology practices: primary results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF).

BACKGROUND: A treatment gap exists between heart failure (HF) guidelines and the clinical care of patients. The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) prospectively tested a multidimensional practice-specific performance improvement intervention on the use of guideline-recommended therapies for HF in outpatient cardiology practices. METHODS AND RESULTS: Performance data were collected in a random sample of HF patients from 167 US outpatient cardiology practices at baseline, longitudinally after intervention at 12 and 24 months, and in single-point-in-time patient cohorts at 6 and 18 months. Participants included 34 810 patients with reduced left ventricular ejection fraction (< or =35%) and chronic HF or previous myocardial infarction. To quantify guideline adherence, 7 quality measures were assessed. Interventions included clinical decision support tools, structured improvement strategies, and chart audits with feedback. The performance improvement intervention resulted in significant improvements in 5 of 7 quality measures at the 24-month assessment compared with baseline: beta-blocker (92.2% versus 86.0%, +6.2%), aldosterone antagonist (60.3% versus 34.5%, +25.1%), cardiac resynchronization therapy (66.3% versus 37.2%, +29.9%), implantable cardioverter-defibrillator (77.5% versus 50.1%, +27.4%), and HF education (72.1% versus 59.5%, +12.6%) (each P<0.001). There were no statistically significant improvements in angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use or anticoagulation for atrial fibrillation. Sensitivity analyses at the patient level and limited to patients with both baseline and 24-month quality measure data yielded similar results. Improvements in the single-point-in-time cohorts were smaller, and there were no concurrent control practices. CONCLUSIONS: The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting, a defined and scalable practice-specific performance improvement intervention, was associated with substantial improvements in the use of guideline-recommended therapies in eligible patients with HF in outpatient cardiology practices. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00303979.

Influence of dedicated heart failure clinics on delivery of recommended therapies in outpatient cardiology practices: findings from the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF).

BACKGROUND: National guidelines recommend heart failure (HF) disease management programs to facilitate adherence to evidence-based practices. This study examined the influence of dedicated HF clinics on delivery of guideline-recommended therapies for cardiology practice outpatients with HF and reduced left ventricular ejection fraction. METHODS: IMPROVE HF, a prospective cohort study, enrolled 167 cardiology practices to characterize outpatient management of 15,381 patients with chronic systolic HF. Adherence to guideline-recommended HF therapies was recorded, and the presence of a dedicated HF clinic was assessed by survey. Multivariate models identified contributions to delivery of guideline-recommended HF therapies. RESULTS: Of practices, 41.3% had a dedicated HF clinic. Practices with a dedicated HF clinic had greater adherence to 3 of 7 guideline-recommended HF therapy measures: angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P = .02), beta-blocker (P = .025), and HF education (P = .009). After adjustment, use of a dedicated HF clinic was associated with greater conformity in 2 of 7 measures: cardiac resynchronization therapy (P = .036) and HF education (P = .005) but not angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, aldosterone antagonist, implantable cardioverter-defibrillator therapy, and anticoagulation for atrial fibrillation. CONCLUSIONS: Use of dedicated HF clinics varied in cardiology outpatient practices and was associated with greater use of cardiac resynchronization therapy and HF education but not other guideline-recommended therapies.

Electronic health records and quality of care for heart failure.

BACKGROUND: Electronic health records (EHRs) are considered an important technology to improve the quality of health care, yet few data exist regarding their effect on delivery of evidence-based care in the outpatient setting. METHODS: IMPROVE HF is a prospective cohort study of 15,381 patients with HF or post myocardial infarction and left ventricular ejection fraction < or =35% cared for in 167 US outpatient cardiology practices. Baseline patient characteristics and quality data were collected by chart abstraction. To quantify care, 7 HF quality measures were assessed; practices with and without EHR were compared. RESULTS: Among practices, 52% had EHR systems (30% EHR-only; 22% both EHR and paper) and 48% paper-only systems. Conformity with indicated care for practices with EHR systems was modestly higher for 2 of 7 quality measures compared to those without. After controlling for patient and site characteristics, use of EHR was associated with improved delivery of 3 of 7 quality measures (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, aldosterone antagonist, and HF education), similar care for 3 measures (beta-blocker, anticoagulation for atrial fibrillation, and cardiac resynchronization therapy), and worse for 1 measure (implantable cardioverter-defibrillator). CONCLUSIONS: These data are among the first to assess the potential influence of EHR on conformity with HF guidelines in the outpatient setting and suggest that EHR systems as currently deployed are associated with only modest differences in some, but not other, quality measures provided to HF patients compared with use of paper-only systems.

Cardiac resynchronization therapy utilization for heart failure: findings from IMPROVE HF.

BACKGROUND: Cardiac resynchronization therapy (CRT) has established efficacy for patients with systolic heart failure (HF). Treatment rates and factors associated with CRT utilization among eligible patients in outpatient cardiology practices have not been well studied. METHODS: IMPROVE HF is a prospective cohort study designed to characterize current management of patients with chronic HF and left ventricular ejection fraction

Prospective evaluation of the association between hemoglobin concentration and quality of life in patients with heart failure.

BACKGROUND: Reduced hemoglobin has been associated with adverse outcomes in heart failure, but the relationship of hemoglobin to health-related quality of life in outpatients with this syndrome has not been well studied. METHODS: We used data from the prospective, observational Study of Anemia in a Heart Failure Population Registry, which randomly selected outpatients with heart failure from specialty or community cardiology clinics. Hemoglobin was determined by finger stick at baseline and during medically indicated follow-up visits. Health-related quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure Questionnaire at 3-month intervals for 12 months. RESULTS: Adjusted regression analysis demonstrated a significant, direct, linear relationship between hemoglobin and health-related quality of life from baseline through 12 months follow-up on all Kansas City Cardiomyopathy Questionnaire domains (all P < .001) and the Summary and Physical domains of the Minnesota Living with Heart Failure Questionnaire (all P < .05). Adjusted categorical analysis of the change in Kansas City Cardiomyopathy Questionnaire Clinical scores associated with change in hemoglobin from baseline to 6 months also showed a significant relationship between increasing hemoglobin and improved health status (5.9 +/- 1.8 units for a hemoglobin increase of >or=1 g/dL, 0.7 +/- 1.2 units for change in hemoglobin <1 g/dL, and -2.6 +/- 1.4 units for a >or=1 g/dL decrease in hemoglobin, P < .001). CONCLUSIONS: These prospective, observational results indicate that reduced hemoglobin is associated with poorer quality of life in patients with heart failure. Additional studies will be required to establish if this is a cause-and-effect relationship.

Influence of patient age and sex on delivery of guideline-recommended heart failure care in the outpatient cardiology practice setting: findings from IMPROVE HF.

BACKGROUND: The influence of patient age and sex on delivery of guideline-recommended heart failure (HF) therapies in contemporary outpatient settings has not been well studied. The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) is a prospective cohort study designed to characterize current management of outpatients with chronic HF and left ventricular ejection fraction < or =35%. METHODS: Baseline data for eligible patients with systolic HF in a national registry of 167 US outpatient cardiology practices were collected by trained chart abstractors. Data were stratified and analyzed as male/female and by age tertiles with generalized estimating equation models constructed for 7 care measures. RESULTS: A total of 15,381 patients were enrolled, with 8,770 (71.1%) of these male. Median age of female patients was 72.0 and 70.0 for males. Use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, aldosterone inhibitors, and cardiac resynchronization therapy was not significantly different between male and female patients, but rates for implantable cardioverter defibrillators, anticoagulation therapy for atrial fibrillation, and HF education were significantly lower for females. After adjusting for patient and practice characteristics, 3 of 7 measures significantly differed by patient sex, and 6 of 7 measures by age. Older patients, particularly older women, were significantly less likely to receive guideline-indicated HF therapies. CONCLUSIONS: Patient age and sex were independently associated with reduced rates of some, but not all, HF therapies in outpatient cardiology practices. Older women are especially at risk. Further research is needed to understand the causes and consequences of these age- and sex-related differences in care.

Influence of coronary angiography on the utilization of therapies in patients with acute heart failure syndromes: findings from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF).

BACKGROUND: Most patients hospitalized for acute heart failure syndromes (AHFS) carry a diagnosis of coronary artery disease (CAD), but coronary angiography is infrequently performed. This purpose of this study was to determine the influence of coronary angiography on use of therapeutics and early postdischarge outcomes in patients with AHFS. METHODS: The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure program enrolled 48,612 patients admitted with AHFS at 259 academic and community hospitals throughout the United States Inhospital treatments and outcomes were tracked in all patients and postdischarge outcomes in a prespecified 10% sample. Outcome data were prospectively collected and analyzed according to whether coronary angiography was performed during the index hospitalization and whether a patient had CAD. RESULTS: Overall, 8.7% of all patients underwent inhospital angiography. Among patients with CAD who underwent angiography, 27.5% underwent inhospital myocardial revascularization. At the time of discharge, patients with CAD who underwent angiography were significantly more likely to be receiving aspirin (68.9% vs 50.3%, P < .0001), statins (56.6% vs 40.6%, P < .0001), beta-blockers (78.6% vs 67.5%, P < .0001), and angiotensin-converting enzyme inhibitors (64.9% vs 51.5%, P < .0001). In patients with AHFS and CAD, the use of inhospital angiography was associated with significantly lower mortality and rehospitalization risk in the first 60 to 90 days post hospital discharge after adjustment for multiple comorbidities and patient factors: mortality (HR 0.31 [95% CI 0.14-0.70], P = .004) and death or rehospitalization (OR 0.65 [95% CI 0.50-0.86], P = .003). There were no significant differences in any of these outcomes in patients with AHFS and a nonischemic etiology based the performance of inhospital angiography. CONCLUSIONS: The performance of inhospital angiography on patients with AHFS and CAD is associated with an increased use of aspirin, statins, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and myocardial revascularization. This corresponded with significantly lower rates of death, rehospitalization, and death or rehospitalization at 60 to 90 days post discharge.