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Background: Conventional composite outcomes in heart failure (HF) trials, for example, time to cardiovascular death or first HF hospitalization, have recognized limitations. We propose an alternative outcome, days alive and out of hospital (DAOH), which incorporates mortality and all hospitalizations into a single measure. A refinement, the patient journey, also uses functional status (New York Heart Association [NYHA] class) measured during follow-up. The CHARM program is used to illustrate the methodology. Methods: CHARM randomized 7,599 patients with symptomatic HF to placebo or candesartan, with median follow-up of 38 months. We related DAOH and percent DAOH (ie, percentage of time spent alive and out of hospital) to treatment using linear regression adjusting for follow-up time. Results: Mean increase in DAOH for patients on candesartan versus placebo was 24.1 days (95% CI 9.8-38.3 days, P < .001). The corresponding mean increase in percent DAOH was 2.0% (95% CI 0.8%-3.1%, P < .001). These findings were dominated by reduced mortality (23 days) but enhanced by reduced time in hospital (1 day). Percent time spent in hospital because of HF was reduced by 0.10% (95% CI 0.04%-0.14%, P < .001). The patient journey analysis showed that patients in the candesartan group spent more follow-up time in NYHA classes I and II and less in NYHA class IV. Conclusions: Days alive and out of hospital, especially percent DAOH, provide a valuable tool for summarizing the overall absolute treatment effect on mortality and morbidity. In future HF trials, percent DAOH can provide a useful alternative perspective on the effects of treatment. [ABSTRACT FROM AUTHOR]

Aims: The mechanisms responsible for the increased risk of heart failure (HF) post–myocardial infarction (MI) may differ between patients with versus without diabetes. We hypothesized that after high-risk MI, patients with diabetes would demonstrate patterns of remodeling that are suggestive of reduced ventricular compliance and that are associated with an increased risk of death or HF. Methods and Results: We performed quantitative echocardiographic analysis in 153 patients with diabetes and 451 patients without diabetes enrolled in the VALIANT Echo study. Diabetes was associated with a higher risk of death or HF in age-adjusted models (hazard ratio 1.44, 95% CI 1.04-2.00, P = .028). Diabetic patients were similar to nondiabetic patients with respect to left ventricular (LV) volume and ejection fraction but had higher LV mass index (104.1 ± 27.5 vs 97.1 ± 28.6 g/m2, P = .009), relative wall thickness (0.41 ± 0.08 vs 0.38 ± 0.07, P < .0001), and left atrial volume index (LAVi) (26.2 ± 8.1 vs 24.0 ± 8.2 mL/m2, P = .008)—all parameters that were significantly related to the risk of death or HF hospitalization. Changes in LV volume and ejection fraction from baseline to 20 months were not different, although diabetic patients demonstrated greater increase in LAVi (4.4 ± 7.7 vs 2.2 ± 6.7 mL/m2, P = .01). Conclusions: After high-risk MI, diabetic patients were at higher risk of death or HF and demonstrated greater baseline LV mass index, relative wall thickness, and LAVi as well as greater left atrial enlargement at 20-month follow-up. These findings suggest greater baseline concentric remodeling and long-term elevation in LV diastolic pressure post-MI among diabetic patients, which may partially mediate this risk. [ABSTRACT FROM AUTHOR]

Background: Echocardiographic measurements of left ventricular (LV) function, predominantly LV ejection fraction (LVEF), have been used to define risk in patients after myocardial infarction. However, the extent to which measures of LV structure and function provide incremental prognostic value over clinical variables in survivors of high-risk myocardial infarction has not been well defined. Methods: Predictors of death and development of heart failure were assessed in 603 patients from the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiographic substudy. We used multivariable proportional hazards models to assess the individual predictive value of echocardiographic measures including left ventricular mass index, LVEF, LV volumes, left atrial volume index, right ventricular fractional area change, mitral regurgitation, and deceleration time. We adjusted for the 11 clinical variables found previously to be most associated with all-cause mortality in this cohort. Receiver operating characteristic curves obtained via binary response regression were used to assess the incremental predictive value of echocardiographic measures in predicting outcomes of death and hospital stay for heart failure. Results: Each echocardiographic measure was independently associated with outcome of death or development of heart failure (all P < .002). Left ventricular ejection fraction alone added minimal prognostic value to the clinical assessment, yet adding additional echocardiographic assessments to a multivariable model improved in predicting 17-month survival free of heart failure significantly, increasing the c-statistic from 0.74 to 0.84 (P < .001). Conclusion: Echocardiographic measures of cardiac structure and function beyond LVEF provide important prognostic information beyond the clinical assessment. [Copyright &y& Elsevier]

Abstract: Background: Alterations in the balance between matrix metalloproteinases and their endogenous tissue inhibitors (TIMPs) are associated with left ventricular (LV) remodeling after acute myocardial infarction (AMI). No relationships have been identified between TIMPs and serial postinfarction change in LV function. Methods and Results: Plasma concentrations of TIMP-1, -2, -4 were measured at baseline (mean 46 h) and at 24 weeks in 100 patients (age 58.9 ± 12 years, 77% male) admitted with AMI and LV dysfunction, with cardiac magnetic resonance imaging at each time point. TIMP-1 concentration was reduced, whereas TIMP-2 and -4 concentrations were elevated at baseline compared with a reference control population. TIMP-1 decreased and TIMP-2 increased significantly over time; there was an incremental trend in TIMP-4 concentration. Baseline TIMP-4 correlated with change in LV end-systolic volume index (∆LVESVI; r = 0.24; P = .023) and change in LV end-diastolic volume index (∆LVEDVI; r = 0.25; P = .015). ∆TIMP-4 also correlated with ∆LVESVI and with ∆LVEDVI, as did ∆TIMP-2. On multivariable analysis, baseline TIMP-4 concentration was an independent predictor of ∆LVESVI. Conclusions: Plasma TIMP-4 concentration, measured early after AMI, may assist in the prediction of LV remodeling and therefore in the assessment of prognosis. Further study of the role of the TIMPs in the pathophysiology of postinfarction remodeling is warranted. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to determine whether coenzyme Q10 is an independent predictor of prognosis in heart failure. Background: Blood and tissue concentrations of the essential cofactor coenzyme Q10 are decreased by statins, and this could be harmful in patients with heart failure. Methods: We measured serum coenzyme Q10 in 1,191 patients with ischemic systolic heart failure enrolled in CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure) and related this to clinical outcomes. Results: Patients with lower coenzyme Q10 concentrations were older and had more advanced heart failure. Mortality was significantly higher among patients in the lowest compared to the highest coenzyme Q10 tertile in a univariate analysis (hazard ratio: 1.50, 95% confidence interval: 1.04 to 2.6, p = 0.03) but not in a multivariable analysis. Coenzyme Q10 was not an independent predictor of any other clinical outcome. Rosuvastatin reduced coenzyme Q10 but there was no interaction between coenzyme Q10 and the effect of rosuvastatin. Conclusions: Coenzyme Q10 is not an independent prognostic variable in heart failure. Rosuvastatin reduced coenzyme Q10, but even in patients with a low baseline coenzyme Q10, rosuvastatin treatment was not associated with a significantly worse outcome. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310) [ABSTRACT FROM AUTHOR]

Background: Myocardial rupture is a relatively rare and usually fatal complication of myocardial infarction (MI). Early recognition of patients at greatest risk of myocardial rupture provides an opportunity for early intervention. Methods: VALIANT was a double-blind, randomized, controlled trial comparing valsartan, captopril, and their combination in high-risk patients post-MI. Myocardial rupture was identified by autopsy (available in 138/589 patients dying within 30 days of index MI), echocardiography, direct surgical visualization, or presence of hemopericardium. An independent clinical end points committee reviewed medical records for all deaths or suspected nonfatal cardiovascular events. Results: Rupture was identified in 45 (0.31%) patients enrolled in VALIANT, occurring 9.8 ± 6.0 days after the qualifying MI. Rupture accounted for 7.6% (45/589) of all deaths occurring in the first 30 days of follow-up and 24% (33/138) of deaths in which autopsies were obtained. Compared with survivors, rupture was associated with increased age, hypertension, increased Killip class, lower estimated glomerular filtration rate, and Q wave MI, and inversely related to β-blocker and diuretic use. Compared with patients who died of other causes within 30 days, patients with myocardial rupture were more likely to have had an inferior MI, Q wave MI, or hypertension; to have used oral anticoagulants; or to have received thrombolytic therapy. Conclusions: Although rare, myocardial rupture accounted for nearly one fourth of all deaths within the first 30 days after high-risk MI, suggesting an estimated incidence of approximately 1% within the first 30 days. A number of clinical characteristics may identify post-MI patients at higher risk of myocardial rupture. [Copyright &y& Elsevier]

Atrial fibrillation (AF) is associated with increased risk of stroke that can be attenuated with vitamin K antagonists (VKAs). Vitamin K antagonist use is limited, in part, by the high incidence of complications when patients'' international normalized ratios (INRs) deviate from the target range. The primary objective of ARISTOTLE is to determine if the factor Xa inhibitor, apixaban, is noninferior to warfarin at reducing the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism in patients with AF and at least 1 additional risk factor for stroke. We have randomized 18,206 patients from over 1,000 centers in 40 countries. Patients were randomly assigned in a 1:1 ratio to receive apixaban or warfarin using a double-blind, double-dummy design. International normalized ratios are monitored and warfarin (or placebo) is adjusted aiming for a target INR range of 2 to 3 using a blinded, encrypted point-of-care device. Minimum treatment is 12 months, and maximum expected exposure is 4 years. Time to accrual of at least 448 primary efficacy events will determine treatment duration. The key secondary objectives are to determine if apixaban is superior to warfarin for the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism, and for all-cause death. These will be tested after the primary objective using a closed test procedure. The noninferiority boundary is 1.38; apixaban will be declared noninferior if the 95% CI excludes the possibility that the primary outcome rate with apixaban is >1.38 times higher than with warfarin. ARISTOTLE will determine whether apixaban is noninferior or superior to warfarin in preventing stroke and systemic embolism; whether apixaban has particular benefits in the warfarin-naïve population; whether it reduces the combined rate of stroke, systemic embolism, and death; and whether it impacts bleeding. [Copyright &y& Elsevier]

Objectives: We investigated whether plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction and prognosis measured in CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), could be used to identify the severity of heart failure at which statins become ineffective. Background: Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transition point at which treatment with a statin becomes futile. Methods: In CORONA, patients with heart failure, reduced left ventricular ejection fraction, and ischemic heart disease were randomly assigned to 10 mg/day rosuvastatin or placebo. The primary composite outcome was cardiovascular death, nonfatal myocardial infarction, or stroke. Results: Of 5,011 patients enrolled, NT-proBNP was measured in 3,664 (73%). The midtertile included values between 103 pmol/l (868 pg/ml) and 277 pmol/l (2,348 pg/ml). Log NT-proBNP was the strongest predictor (per log unit) of every outcome assessed but was strongest for death from worsening heart failure (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.71 to 2.30), was weaker for sudden death (HR: 1.69; 95% CI: 1.52 to 1.88), and was weakest for atherothrombotic events (HR: 1.24; 95% CI: 1.10 to 1.40). Patients in the lowest tertile of NT-proBNP had the best prognosis and, if assigned to rosuvastatin rather than placebo, had a greater reduction in the primary end point (HR: 0.65; 95% CI: 0.47 to 0.88) than patients in the other tertiles (heterogeneity test, p = 0.0192). This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin. Conclusions: Patients with heart failure due to ischemic heart disease who have NT-proBNP values <103 pmol/l (868 pg/ml) may benefit from rosuvastatin. [Copyright &y& Elsevier]

Background: Acute decompensated heart failure (ADHF) is a major public health burden with significant mortality and morbidity. Nesiritide is a recombinantly produced intravenous formulation of human B-type natriuretic peptide that promotes vasodilation and increases salt and water excretion, which results in reduced cardiac filling pressures. Prior studies have shown that dyspnea is improved in patients with ADHF 3 hours after nesiritide infusion with significant dose-related reductions in cardiac filling pressures and systemic vascular resistance without significant arrhythmias. However, the effect of nesiritide on dyspnea at 6 or 24 hours is unknown, and no clinical outcome trials have been done to provide a reliable estimate of the effect of nesiritide on morbidity and mortality. Methods: The Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure trial (ASCEND-HF) is a phase III study evaluating the efficacy and safety of nesiritide in patients with ADHF. Patients hospitalized for hear failure will be randomly assigned to receive either intravenous nesiritide or matching placebo for 24 hours to 7 days. The 2 coprimary end points are (1) assessment of acute dyspnea at 6 or 24 hours and (2) death or rehospitalization for hear failure within 30 days. A total of 7,000 patients will be enrolled worldwide between 2007 and 2010. Conclusions: The data from the ASCEND-HF trial will establish whether nesiritide safely improves acute dyspnea as well as morbidity and mortality at 30 days. [Copyright &y& Elsevier]

FREEDOM, a cardiovascular outcome trial with a GLP-1 receptor agonist, testing a continuous subcutaneous infusion of exenatide (ITCA 650), recently reported its findings. We meta-analysed its results with eight prior GLP-1 receptor agonists trials. GLP-1 receptor agonists reduced MACE by 13% (HR 0.87 [95% CI 0.81–0.94]; p = 0.00065) and all-cause mortality by 11% (HR 0.89 [0.83–0.95]; p = 0.00084). However, FREEDOM results appear dissimilar to prior GLP-1 receptor agonist trials. FREEDOM results should not influence current considerations about the benefits or harms of approved formulations of GLP-1 receptor agonists. There is also an ongoing debate about the safety of ITCA 650. • The FREEDOM Cardiovascular Outcomes trial results were recently published. • Its results appear different to other GLP-1 receptor agonist outcome trials in a trial meta-analysis. • This and other concerns mean FREEDOM should not influence current perceptions about the benefits of GLP-1 receptor agonists. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to understand prognostic implications of increased baseline left ventricular (LV) mass and geometric patterns in a high risk acute myocardial infarction. Background: The LV hypertrophy and alterations in LV geometry are associated with an increased risk of adverse cardiovascular events. Methods: Quantitative echocardiographic analyses were performed at baseline in 603 patients from the VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study. The left ventricular mass index (LVMi) and relative wall thickness (RWT) were calculated. Patients were classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). Cox proportional hazards models were used to evaluate the relationships among LVMi, RWT, LV geometry, and clinical outcomes. Results: Mean LVMi and RWT were 98.8 ± 28.4 g/m2 and 0.38 ± 0.08. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, heart failure, stroke, or resuscitation after cardiac arrest was lowest for patients with normal geometry, and increased with concentric remodeling (hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.9 to 4.9), eccentric hypertrophy (HR: 3.1; 95% CI: 1.9 to 4.8), and concentric hypertrophy (HR: 5.4; 95% CI: 3.4 to 8.5), after adjusting for baseline covariates. Also, baseline LVMi and RWT were associated with increased mortality and nonfatal cardiovascular outcomes (HR: 1.22 per 10 g/m2 increase in LVMi; 95% CI: 1.20 to 1.30; p < 0.001) (HR: 1.60 per 0.1-U increase in RWT; 95% CI: 1.30 to 1.90; p < 0.001). Increased risk associated with RWT was independent of LVMi. Conclusions: Increased baseline LV mass and abnormal LV geometry portend an increased risk for morbidity and mortality following high-risk myocardial infarction. Concentric LV hypertrophy carries the greatest risk of adverse cardiovascular events including death. Higher RWT was associated with an increased risk of cardiovascular complications after high-risk myocardial infarction. [Copyright &y& Elsevier]

Background: Advanced age is a well-established prognostic risk factor after acute myocardial infarction (AMI), yet approximately 10% of MIs occur in patients <45 years. We examined characteristics, cardiovascular outcomes, and the influence of risk factors on outcomes in young survivors of AMI. Methods: Fourteen thousand seven hundred three patients enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial were divided into 3 age groups: 18 to <45 (n = 803), 45 to <65 (n = 6185), ≥65 years (n = 7715). Multivariate Cox regression was used to compare cardiovascular event rates and assess the impact of risk factors on outcomes. Results: The youngest patients had less diabetes, hypertension, and history of MI and were more likely to be male (18 to <45 years, 88%; ≥65 years, 59.1%), nonwhite (18 to <45 years, 9.6%; ≥65 years, 5%), current smokers (18 to <45 years, 73.7%; ≥65 years, 15.9%), obese (18 to <45 years, 37.9%; ≥65 years, 25.1%), and dyslipidemic at randomization (18 to <45 years, 43.1%; ≥65 years, 32.7%). Adjusted relative risks of smoking (18 to <45 years, hazard ratio [HR] 1.6 [95% confidence interval {CI} 1.1-2.5]; ≥45 years, HR 0.9 [95% CI 0.9-1.1]; P =.014) and hypertension (18 to <45 years, HR 1.8 [95% CI 1.3-2.6]; ≥45 years, HR 1.2 [95% CI 1.1-1.3]; P = .044) were higher in the young, with significant interactions observed between age and these risk factors. Conclusions: After AMI, risk factors and outcomes of the young differ substantively from their older counterparts. The influence of hypertension and smoking is more profound in the young, underscoring the need for aggressive risk factor modification post-AMI. [Copyright &y& Elsevier]

Background: We sought to assess the association of amiodarone use with mortality during consecutive periods in patients with post–acute myocardial infarction with left ventricular systolic dysfunction and/or HF treated with a contemporary medical regimen. Methods: This study used data from VALIANT, a randomized comparison of valsartan, captopril, or both in patients with acute myocardial infarction with HF and/or left ventricular systolic dysfunction. We compared baseline characteristics of 825 patients treated with amiodarone at randomization with 13 875 patients not treated with amiodarone. Using Cox models, we examined the association of amiodarone use with subsequent mortality during consecutive periods after randomization (days 1-16, 17-45, 46-198, and 199-1096). Results: Patients treated with amiodarone were older, had higher Killip class, and were more likely to have a history of diabetes mellitus and hypertension. Adjusting for baseline predictors of mortality, we found that amiodarone use was associated with a significant increase in mortality during 3 of the 4 periods: hazard ratio 1.5, 95% CI (1.1-2.0), P = .02, for days 1 to 16; 2.1 (1.5-2.9), P < .001, for days 17 to 45; 1.1 (0.83-1.46), P = .51, for days 46 to 198; and 1.4 (1.2-1.6), P < .001, for days 199 to 1096. Conclusion: In this study, amiodarone use was associated with excess early and late all-cause and cardiovascular mortality. These observational findings are in contrast to earlier randomized trials of amiodarone and need to be validated prospectively. [Copyright &y& Elsevier]

Background: In survivors of myocardial infarction (MI), new left bundle branch block (LBBB) is associated with adverse outcomes, but its impact is not well described in post-MI patients with left ventricular (LV) systolic dysfunction and/or heart failure (HF).Objectives: The aim of this study was to determine if new LBBB is an independent predictor of long-term fatal and nonfatal outcomes in high-risk survivors of MI by reviewing data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial.Methods: In VALIANT, 14,703 patients with LV systolic dysfunction and/or HF were randomized to valsartan, captopril, or both a mean of 5 days after MI. Baseline ECG data were available from 14,259 patients. We assessed the predictive value of new LBBB for death and major cardiovascular outcomes after 3 years, adjusting for multiple baseline covariates including LV ejection fraction.Results: At follow-up, patients with new LBBB (608 [4.2%]) compared with patients without new LBBB had more comorbidities and increased adjusted risk of death (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.2-1.6), cardiovascular death (HR 1.4, 95% CI 1.2-1.7), HF (HR 1.3, 95% CI 1.1-1.6), MI (HR 1.5, 95% CI 1.2-1.9), and the composite of death, HF, or MI (HR 1.4, 95% CI 1.2-1.6).Conclusion: In post-MI survivors with LV systolic dysfunction and/or HF, new LBBB was an independent predictor of all major adverse cardiovascular outcomes during long-term follow-up. This readily available ECG marker should be considered a major risk factor for long-term cardiovascular complications in high-risk patients after MI. [ABSTRACT FROM AUTHOR]

Omecamtiv mecarbil (OM) is a cardiac myotrope which selectively activates cardiac myosin and thereby increases cardiac contractility. The aim of the current study was to determine the effect of therapy with OM on right ventricular (RV) structure and function in patients with heart failure (HF). In the COSMIC-HF trial, 448 patients with stable, symptomatic HF and left ventricular ejection fraction (LVEF) <40% were randomly assigned to double-blind oral OM [25 mg twice daily; or 25 mg twice daily with pharmacokinetic-guided uptitration to 50 mg twice daily (PK group)] or placebo for 20 weeks. RV systolic ejection time (RV-SET), TAPSE, RV end-systolic (RV-ESA) and end-diastolic area (RV-EDA), RV outflow tract velocity time integral (RVOT-VTI), pulmonary arterial systolic pressure (PASP), TAPSE/PASP ratio and RVOT-VTI/PASP ratio were assessed between the placebo (n=149), the 25 mg group (n=150) and the PK group (n=149) at week 20. Patients were 63±11 years old with LVEF of 29.1±7.3%. OM had no effect on RV-EDA nor TAPSE (Figure). However, OM significantly improved several measures of RV function such as RV-SET, RV-ESA, RVOT-VTI together with measures of RV pulmonary arterial coupling (PASP, TAPSE/PASP ratio and RVOT-VTI/PASP ratio) (Figure). In patients with chronic HF and reduced systolic function, 20 weeks of OM treatment was associated with improvement in several measures of RV function together with improvement in measures of RV pulmonary arterial coupling. [ABSTRACT FROM AUTHOR]

With an increasing burden of cardiovascular disease and many promising novel treatments in development, the need for efficient systems to evaluate treatments has never been greater. To understand whether a treatment should be used in practice, we need to know whether it makes patients live longer, feel better, prevents adverse events, or does these things with better tolerability or lower cost. But therapeutic development is expensive, inefficient, and is generally focused on short-term treatment effects, rather than on prevention and on long-term impact. Could measures of disease progression, combined with trends on clinical outcomes and post-marketing surveillance to assess safety, serve as the foundation for therapeutic development? Experience and principles of clinical research tell us no. Especially in the field of heart failure, numerous treatments have appeared promising based on disease markers, yet caused harm when tested in studies that assessed clinical outcomes. The intersection of complex human disease, intended and unintended targets of therapy, and overall risk and benefit make it impossible to accurately predict the effect on clinical outcomes based on impact on a disease marker. While reliable measures of disease progression are important to guide which treatments to study in trials, clinical outcome trials must remain the basis for informing clinicians on which treatments improve clinical outcomes. Improved reliability and capacity require the development of more efficient clinical trial methods, streamlined regulatory processes, rational use of privacy protection, leveraging of electronic medical records, and recruitment of a larger proportion of the clinical community to participate in clinical trials. [Copyright &y& Elsevier]

The development of heart failure and/or left ventricular systolic dysfunction (LVSD) in the setting of acute myocardial infarction (AMI) results in significant risk far above that of AMI independently. In patients admitted to the hospital for AMI, concomitant heart failure and/or LVSD on hospital admission or development of either or both of these conditions during admission are among the strongest predictors of inhospital death and are associated with significant increases in inhospital, 30-day, and long-term mortality and rehospitalization rates. Given the high risks in this population, aggressive treatment, comprising early initiation and sustained use of evidence-based treatments, is essential for improving prognosis. [Copyright &y& Elsevier]

Background: In a multinational clinical trial, valsartan was statistically not inferior to captopril in reducing mortality and cardiovascular morbidity after myocardial infarction (MI) in patients with signs of heart failure and/or left ventricular dysfunction. We conducted a prospective economic evaluation to compare within-trial resource use, costs, and quality of life in patients receiving valsartan, captopril, or both after MI. Methods: We assigned country-specific unit costs to resource use data for 14703 patients and measured health-related quality of life in a subset of 4524 patients. We used the nonparametric bootstrap method to compare rates of resource use and costs, and a piecewise linear mixed-effects regression analysis to compare longitudinal measures of quality of life. Results: There were no significant differences in rates of resource use between the valsartan and captopril groups. During an average follow-up of 2 years, total costs for patients receiving valsartan were significantly higher than for patients receiving captopril (US$14103 vs US$13038; 95% CI US$369-US$1875). The cost differential was caused primarily by the cost of the study medications (US$1056 for valsartan vs US$165 for captopril; 95% CI US$867 to US$912). Quality of life did not differ significantly between groups. Conclusions: For most patients at high risk after MI, the availability of generic captopril confers a cost advantage over valsartan because of lower medication costs. The difference will be smaller or nonexistent in settings where brand-name ACE inhibitors are prescribed. [Copyright &y& Elsevier]

Abstract: Background: The aim of this study was to determine the effects of carvedilol on the costs related to the treatment of severe chronic heart failure (CHF). Methods: Costs for the treatment for heart failure within the National Health Service (NHS) in the United Kingdom (UK) were applied to resource utilisation data prospectively collected in all patients randomized into the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study. Unit-specific, per diem (hospital bed day) costs were used to calculate expenditures due to hospitalizations. We also included costs of carvedilol treatment, general practitioner surgery/office visits, hospital out-patient clinic visits and nursing home care based on estimates derived from validated patterns of clinical practice in the UK. Results: The estimated cost of carvedilol therapy and related ambulatory care for the 1156 patients assigned to active treatment was £530,771 (£44.89 per patient/month of follow-up). However, patients assigned to carvedilol were hospitalised less often and accumulated fewer and less expensive days of admission. Consequently, the total estimated cost of hospital care was £3.49 million in the carvedilol group compared with £4.24 million for the 1133 patients in the placebo arm. The cost of post-discharge care was also less in the carvedilol than in the placebo group (£479,200 vs. £548,300). Overall, the cost per patient treated in the carvedilol group was £3948 compared to £4279 in the placebo group. This equated to a cost of £385.98 vs. £434.18, respectively, per patient/month of follow-up: an 11.1% reduction in health care costs in favour of carvedilol. Conclusions: These findings suggest that not only can carvedilol treatment increase survival and reduce hospital admissions in patients with severe CHF but that it can also cut costs in the process. [Copyright &y& Elsevier]

Impaired endothelial function in isolated human uremic resistance arteries. Background. Patients with chronic renal failure (CRF) face a markedly increased risk of cardiovascular death. CRF is frequently complicated by hypertension and changes in both the heart (left ventricular hypertrophy) and the vasculature (endothelial dysfunction and accelerated atherosclerosis). The mechanisms underlying changes in vascular function and specifically endothelial dysfunction are unclear. This present study therefore examined subcutaneous resistance artery function in vitro, comparing adult uremic patients and controls using wire myography. Methods. Subcutaneous fat biopsies were obtained from 12 patients with CRF (median serum creatinine 735 μmol/L) at the time of renal transplantation or peritoneal dialysis catheter insertion, and from eight controls without renal disease at the time of abdominal surgery. Resistance arteries were mounted on a wire myograph. Their contractile ability was tested with high potassium depolarization, and endothelial integrity was tested by relaxation to acetylcholine. Cumulative concentration-response curves were then constructed for norepinephrine, endothelin-1, acetylcholine, and sodium nitroprusside (SNP). Results. Following preconstriction with norepinephrine, vessels from uremic patients vasodilated less well to acetylcholine compared with vessels from controls [maximum % relaxation 77% (range 41, 97) vs. 98% (78, 100), P < 0.001]. The vasodilation to SNP was similar [95% (63, 100) vs. 94% (71, 100), P = 0.751]. There was a trend toward increased maximum pressure (kPa) achieved with both norepinephrine and endothelin-1 in vessels from uremic patients, and the contractions to both of these agents were more prolonged in the uremic vessels. Conclusions. The pattern of normal vasodilation to SNP but reduced vasodilation to acetylcholine is consistent with endothelial dysfunction due to impaired nitric oxide (NO) production in uremic... [ABSTRACT FROM AUTHOR]

Endothelial dysfunction in renal transplant recipients maintained on cyclosporine. Background. Hypertension is almost universal following renal transplantation and may contribute to the already poor cardiovascular prognosis of this group. Cyclosporine-induced hypertension is a particular problem and has variously been attributed to increased sympathetic nerve activity, salt and water retention, and increased circulating endothelin levels. However, the effects of cyclosporine on the l-arginine/nitric oxide (NO) system in vivo in humans are unknown. In this present study, we examined basal and stimulated NO production from the vascular endothelium in cyclosporine-treated renal transplant recipients using the technique of forearm venous plethysmography. Methods. In study 1, stimulated NO production was assessed in 9 cyclosporine-treated renal transplant recipients (CsA), 7 azathioprine-treated renal transplant recipients (AZA), and 12 controls, using carbachol (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator). In study 2, basal NO production was assessed in 9 cyclosporine-treated patients and 11 controls using l-NMMA (inhibits NO synthase), with norepinephrine as a control vasoconstrictor. Drugs were infused into the nondominant forearm through a sterile 27-gauge needle, and changes in forearm blood flow (FBF) were measured using venous occlusion plethysmography. Results. In study 1, sodium nitroprusside caused a similar dose-dependent increase in FBF in all groups. However, the median (range) percentage increase FBF to carbachol (3 μg/min) was markedly reduced in the CsA patients (188.8; 72.5 to 385.1) compared with AZA patients (378.1; 124.0 to 548.9; P = 0.042) and to controls (303.8; 124.8 to 813.3; P = 0.028). In study 2, the maximum percentage reduction in FBF to l-NMMA (4 μmol/min) was less pronounced in CsA patients (-19.5; -4.7 to -63.1) compared with controls (- 39.5; -15.7 to -52.8; P =... [ABSTRACT FROM AUTHOR]

Kidney dysfunction often leads to reluctance to start or continue life-saving heart failure (HF) therapy. This study sought to examine the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with HF with reduced ejection fraction experiencing significant kidney dysfunction. We pooled individual patient data from the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials. The association between MRA treatment and outcomes was assessed according to whether the estimated glomerular filtration rate (eGFR) declined to <30 mL/min/1.73 m2 or not. The primary outcome was cardiovascular death or HF hospitalization. Among 4,355 patients included, 295 (6.8%) experienced a deterioration of eGFR after randomization to <30 mL/min/1.73 m2. These patients had more impaired baseline cardiac and kidney function (eGFR 47.3 ± 13.4 mL/min/1.73 m2 vs 70.5 ± 21.8 mL/min/1.73 m2) and had a higher risk of the primary outcome than patients without eGFR deterioration (HR: 2.49; 95% CI: 2.01-3.08; P < 0.001). However, the risk reduction in the primary outcome with MRA therapy was similar in those who experienced a decrease in eGFR to <30 mL/min/1.73 m2 (HR: 0.65; 95% CI: 0.43-0.99) compared with those who did not (HR: 0.63; 95% CI: 0.56-0.71) (P interaction = 0.87). In patients with a decrease in eGFR to <30 mL/min/1.73 m2, 21 fewer individuals (per 100 person-years) experienced the primary outcome with MRA treatment, vs placebo, compared with an excess of 3 more patients with severe hyperkalemia (>6.0 mmol/L). Because patients experiencing a decrease in eGFR to <30 mL/min/1.73 m2 are at very high risk, the absolute risk reduction with an MRA in these patients is large and this decline in eGFR should not automatically lead to treatment discontinuation. [Display omitted] [ABSTRACT FROM AUTHOR]

The Kidney Disease Improving Global Outcomes (KDIGO) classification integrates both estimated glomerular filtration rate and urine-albumin-creatinine ratio to stratify risk more comprehensively in patients with chronic kidney disease. There are limited data assessing whether this classification system is associated with prognosis and treatment response in heart failure populations. The aim of this study was to evaluate the relative treatment effects of sacubitril/valsartan across the KDIGO risk categories in patients with HFrEF. PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) was a global randomized controlled trial evaluating sacubitril/valsartan vs enalapril in patients with heart failure with reduced ejection fraction (HFrEF). Patients were classified according to low, moderate, and high/very high KDIGO risk. Treatment responses were assessed according to baseline KDIGO risk. The primary outcome was a composite of cardiovascular (CV) death or heart failure hospitalization. A renal composite outcome was defined as sustained decline in estimated glomerular filtration rate by ≥40% or end-stage kidney disease. Among 1,910 (23% of total) participants with available data, 42%, 32%, and 26% were classified as low, moderate, and high/very high KDIGO risk, respectively. Patients in the highest KDIGO risk categories experienced the highest rates of the primary composite outcome (7.6 per 100 person-years [95% CI: 6.5-9.0 per 100 person-years], 9.4 per 100 person-years [95% CI: 7.9-11.2 per 100 person-years], and 14.9 per 100 person-years [95% CI: 12.7-17.6 per 100 person-years]; P < 0.001). Sacubitril/valsartan had a similar safety profile and demonstrated consistent effects on the risk of both the primary outcome (P Interaction = 0.31) and the renal composite outcome (P Interaction = 0.50) across the spectrum of KDIGO risk. One in 4 patients with HFrEF were classified as at least high KDIGO kidney risk; these individuals faced concordantly the highest risks of CV events. Sacubitril/valsartan exhibited consistent CV and kidney protective benefits as well as safety across the spectrum of baseline kidney risk. These data further support initiation of sacubitril/valsartan in HFrEF across a broad range of kidney risk. (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF]; NCT01035255) [Display omitted] [ABSTRACT FROM AUTHOR]

Conventional time-to-first-event analyses cannot incorporate recurrent hospitalizations and patient well-being in a single outcome. To overcome this limitation, we tested an integrated measure that includes days lost from death and hospitalization, and additional days of full health lost through diminished well-being. The effect of dapagliflozin on this integrated measure was assessed in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial, which examined the efficacy of dapagliflozin, compared with placebo, in patients with NYHA functional class II to IV heart failure and a left ventricular ejection fraction ≤40%. Over 360 days, patients in the dapagliflozin group (n = 2,127) lost 10.6 ± 1.0 (2.9%) of potential follow-up days through cardiovascular death and heart failure hospitalization, compared with 14.4 ± 1.0 days (4.0%) in the placebo group (n = 2,108), and this component of all measures of days lost accounted for the greatest between-treatment difference (−3.8 days [95% CI: −6.6 to −1.0 days]). Patients receiving dapagliflozin also had fewer days lost to death and hospitalization from all causes vs placebo (15.5 ± 1.1 days [4.3%] vs 20.3 ± 1.1 days [5.6%]). When additional days of full health lost (ie, adjusted for Kansas City Cardiomyopathy Questionnaire–overall summary score) were added, total days lost were 110.6 ± 1.6 days (30.7%) with dapagliflozin vs 116.9 ± 1.6 days (32.5%) with placebo. The difference in all measures between the 2 groups increased over time (ie, days lost by death and hospitalization −0.9 days [−0.7%] at 120 days, −2.3 days [−1.0%] at 240 days, and −4.8 days [−1.3%] at 360 days). Dapagliflozin reduced the total days of potential full health lost due to death, hospitalizations, and impaired well-being, and this benefit increased over time during the first year. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure; NCT03036124) [Display omitted] [ABSTRACT FROM AUTHOR]

Hypotension is a potential adverse effect of sacubitril/valsartan, but there are limited data regarding the predictors and implications of treatment-related hypotension in heart failure (HF) with mildly reduced and preserved ejection fraction. We investigated predictors of treatment-associated hypotension, clinical outcomes after hypotension, and the relationship between left ventricular ejection fraction (LVEF) and incidence of hypotension in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial. PARAGON-HF randomized patients with chronic HF (≥45%) to sacubitril/valsartan or valsartan. Following randomization, hypotension was defined as investigator-reported hypotension with a systolic blood pressure <100 mm Hg. Predictors of hypotension were assessed using multivariable Cox models. Associations between hypotension and clinical outcomes were evaluated in time-updated Cox models. The relationship among treatment, LVEF, and incident rates of hypotension and clinical outcomes was estimated using Poisson regression models. Of 4,796 patients in PARAGON-HF, 637 (13%) experienced hypotension, more frequently in the sacubitril/valsartan arm (P < 0.001). Following documented hypotension, patients had higher risk of cardiovascular death and total HF hospitalizations (adjusted RR: 1.63; 95% CI: 1.27-2.09; P < 0.001) and all-cause death (adjusted HR: 1.62; 95% CI: 1.28-2.05; P < 0.001). LVEF modified the association between sacubitril/valsartan and risk of hypotension (P interaction = 0.019) such that patients with LVEF ≥60% experienced substantially higher treatment-related risks of hypotension. In PARAGON-HF, a higher LVEF was associated with an increased risk of hypotension in patients treated with sacubitril/valsartan compared with valsartan. Because these subjects are also less likely to derive clinical benefit from sacubitril/valsartan, our data reinforce that the benefit/risk ratio favors the use of sacubitril/valsartan in patients with LVEF below normal, but not at higher LVEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711) [Display omitted] [ABSTRACT FROM AUTHOR]

Patients who sustain an acute myocardial infarction (AMI), including ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation myocardial infarction (NSTEMI), remain at high risk for heart failure (HF), coronary events, and death. Angiotensin-converting enzyme inhibitors have been shown to significantly decrease the risk for cardiovascular events in both STEMI and NSTEMI patients. The objectives were to determine whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan, compared with ramipril, has impact on reducing cardiovascular events according to the type of AMI. The PARADISE-MI (Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction) trial enrolled patients with AMI complicated by left ventricular dysfunction and/or pulmonary congestion and at least 1 risk-enhancing factor. Patients were randomized to either sacubitril/valsartan or ramipril. The primary endpoint was death from cardiovascular causes or incident HF. In this prespecified analysis, we stratified patients according to AMI type. Of 5,661 enrolled patients, 4,291 (75.8%) had STEMI. These patients were younger and had fewer comorbidities and cardiovascular risk factors than NSTEMI patients. After adjustment for potential confounders, the risk for the primary outcome was marginally higher in NSTEMI vs STEMI patients (adjusted HR: 1.19; 95% CI: 1.00-1.41), with borderline statistical significance (P = 0.05). The primary composite outcome occurred at similar rates in patients randomized to sacubitril/valsartan vs ramipril in STEMI (10% vs 12%; HR: 0.87; 95% CI: 0.73-1.04; P = 0.13) and NSTEMI patients (17% vs 17%; HR: 0.97; 95% CI: 0.75-1.25; P = 0.80; P interaction = 0.53). Compared with ramipril, sacubitril/valsartan did not significantly decrease the risk for cardiovascular death and HF in patients with AMI complicated by left ventricular dysfunction, irrespective of the type of AMI. (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI; NCT02924727) [Display omitted] [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are guideline recommended in the management of heart failure (HF). Although these therapies can be initiated even in patients with comorbid chronic kidney disease, some patients may face deterioration of kidney function over time. In this study, the authors sought to examine the safety and efficacy of continuing SGLT2 inhibitors in HF when the estimated glomerular filtration rate (eGFR) falls below thresholds for initiation. Associations between a deterioration of eGFR to <25 mL/min/1.73 m2, efficacy, and safety outcomes and treatment with dapagliflozin were evaluated in time-updated Cox proportional hazard models in a participant-level pooled analysis of the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials. Among 11,007 patients, 347 (3.2%) experienced a deterioration of eGFR to <25 mL/min/1.73 m2 at least once in follow-up. These patients had a higher risk of the primary composite outcome (HR: 1.87; 95% CI: 1.48-2.35; P < 0.001). The risk of the primary outcome was lower with dapagliflozin compared with placebo among patients who did (HR: 0.53; 95% CI: 0.33-0.83) as well as did not (HR: 0.78; 95% CI: 0.72-0.86) experience deterioration of eGFR to <25 mL/min/1.73 m2 (P interaction = 0.17). The risk of safety outcomes, including drug discontinuation, was higher among patients with deterioration of eGFR to <25 mL/min/1.73 m2; however, rates remained similar between treatment groups including among those who remained on study drug. Patients with deterioration of eGFR to <25 mL/min/1.73 m2 had elevated risks of cardiovascular outcomes yet appeared to benefit from continuation of dapagliflozin with no excess in safety outcomes between treatment groups. The benefit-to-risk ratio may favor continuation of dapagliflozin treatment in patients with HF experiencing deterioration of kidney function. Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124 ; and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213) [Display omitted] [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP-1 RAs) reduce adverse cardiovascular outcomes in type 2 diabetes (T2D). However, the efficacy of combination therapy is unclear. The aim of this study was to evaluate the effects of GLP-1 RAs on cardiovascular outcomes in patients with T2D treated with or without SGLT2 inhibitors. Post hoc analysis of Harmony Outcomes (Albiglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease) evaluating the effect of albiglutide in T2D with cardiovascular disease by background SGLT2 inhibitor use. Additionally, a trial-level meta-analysis of Harmony Outcomes and AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes), which evaluated T2D with cardiovascular or renal disease, was performed, combining the treatment effect estimates according to SGLT2 inhibitor use. Of the 9,462 participants in Harmony Outcomes, 575 (6.1%) were treated with SGLT2 inhibitors at baseline. The effect of albiglutide on reducing the composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events) was consistent with or without SGLT2 inhibitors (P interaction = 0.70). The effect of albiglutide on secondary outcomes and adverse events was not modified by SGLT2 inhibitors. A meta-analysis of Harmony Outcomes and AMPLITUDE-O included 13,538 patients, of whom 1,193 (8.8%) used SGLT2 inhibitors. Compared to placebo, GLP1-RAs reduced major adverse cardiovascular events without effect modification by SGLT2 inhibitor use (HR: 0.77; 95% CI: 0.68-0.87 without SGLT2 inhibitors; and HR: 0.78; 95% CI: 0.49-1.24 with SGLT2 inhibitors) (P for interaction = 0.95) and reduced heart failure hospitalization (HR: 0.72; 95% CI: 0.55-0.92 vs HR: 0.34; 95% CI: 0.12-0.96) (P for interaction = 0.18). In patients with T2D and cardiovascular disease, GLP-1 RAs reduced cardiovascular events independently of SGLT2 inhibitor use. These findings suggest that the combination of GLP-1 RAs with SGLT2 inhibitors may further reduce cardiovascular risk. Clinical trials with combination therapy are needed. [Display omitted] [ABSTRACT FROM AUTHOR]

Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). This study sought to assess the clinical implications of RV function, the association with N-terminal pro–B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF. This study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro–B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders. Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro–B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function. Worsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711) [Display omitted] [ABSTRACT FROM AUTHOR]

Background The incidence of end-stage renal disease (ESRD) has been consistently shown to be higher among blacks and Hispanics compared to whites with unmeasured risk factors and access to care as suggested explanations. In a high-risk cohort with frequent protocol-directed follow-up, we evaluated the influence of race on cardiovascular (CV) outcomes and incidence of ESRD. Methods TREAT was a randomized, double-blind, placebo-controlled study. This secondary analysis focused on role of race on outcomes. TREAT enrolled 4,038 patients with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate 20-60 mL/min per 1.73 m 2 ), and anemia (hemoglobin level ≤11 g/dL) treated with either darbepoetin alfa or placebo. We compared self-described black and Hispanic patients to white patients with regard to baseline characteristics and outcomes, including mortality, CV outcomes (myocardial infarction, stroke, heart failure, resuscitated sudden death, and coronary revascularization), and incident ESRD. Multivariate adjusted Cox models were developed for these outcomes. Results Black and Hispanic patients were younger, more likely women, had less prior CV disease, and higher blood pressure. During a mean follow-up of 2.4 years with comparable access to care, blacks and Hispanics had a greater risk of ESRD but a significant lower risk of myocardial infarction and coronary revascularization than whites. After adjusting for confounders, blacks remained at significantly greater risk of ESRD than whites (hazard ratio 1.53, 95% CI 1.26-1.85, P < .001), whereas this ESRD risk did not persist among Hispanics. Conclusion Despite similar access to care and lower CV event rates, the risk of ESRD was higher among blacks and Hispanics than whites. For blacks, but not Hispanics, this increase was independent of known attributable risk factors. [ABSTRACT FROM AUTHOR]