| 1. |
- O'Connor, C. M., et al.
(författare)
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Effect of nesiritide in patients with acute decompensated heart failure
- 2011
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P
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| 2. |
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| 3. |
- Rogers, J. K., et al.
(författare)
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Effect of rosuvastatin on repeat heart failure hospitalizations: The CORONA trial (controlled rosuvastatin multinational trial in heart failure)
- 2014
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Ingår i: JACC: Heart Failure. - : Elsevier Inc.. - 2213-1787 .- 2213-1779. ; 2:3, s. 289-297
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study sought to examine the effect of statin therapy hospitalizations for heart failure (HFH) in patients in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) trial. Background: HFH is an important, frequently recurrent event. Conventional time-to-first event analyses do not take account repeat events. We used a number of statistical approaches to examine the effect of treatment on first and repeat HFH in the CORONA trial. Methods: In the CORONA trial, 5,011 patients ≥60 years of age with chronic New York Heart Association functional classes II to IV systolic heart failure resulting from ischemia were randomized to receive rosuvastatin or placebo. Poisson, Andersen-Gill, and negative binomial methods (NB) were used to analyze the effect of rosuvastatin on HFH, and the NB and a parametric joint frailty model (JF) were used to examine this effect while accounting for the competing risk of cardiovascular (CV) death. Rosuvastatin/placebo rate ratios were calculated, both unadjusted and adjusted. Results: A total of 1,291 patients had 1 or more HFH (750 of these had a single HFH only), and there were a total of 2,408 HFHs. The hazard ratio for the conventional time-to-first event analysis for HFH was 0.91 (95% confidence interval [CI]: 0.82 to 1.02, p = 0.105). In contrast, the NB on repeat hospitalizations gave an unadjusted RR (RR) for HFH of 0.86 (95% CI: 0.75 to 0.99, p = 0.030), adjusted 0.82 (95% CI: 0.72 to 0.92, p = 0.001), and after including CV death as the last event, adjusted RR of 0.85 (95% CI: 0.77 to 0.94, p = 0.001). The JF gave an adjusted RR of 0.82 (95% CI: 0.73 to 0.92, p = 0.001). Similar results were found in analyses of all CV hospitalizations and all-cause hospitalizations. Conclusions: When repeat events were included, rosuvastatin was shown to reduce the risk of HFH by approximately 15% to 20%, equating to approximately 76 fewer admissions per 1,000 patients treated over a median 33 months of follow-up. Including repeat events could increase the ability to detect treatment effects in heart failure trials. © 2014 American College of Cardiology Foundation.
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| 4. |
- Zannad, F., et al.
(författare)
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Clinical outcome endpoints in heart failure trials: a European Society of Cardiology Heart Failure Association consensus document
- 2013
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 15:10, s. 1082-1094
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Tidskriftsartikel (refereegranskat)abstract
- Endpoint selection is a critically important step in clinical trial design. It poses major challenges for investigators, regulators, and study sponsors, and it also has important clinical and practical implications for physicians and patients. Clinical outcomes of interest in heart failure trials include all-cause mortality, cause-specific mortality, relevant non-fatal morbidity (e.g. all-cause and cause-specific hospitalization), composites capturing both morbidity and mortality, safety, symptoms, functional capacity, and patient-reported outcomes. Each of these endpoints has strengths and weaknesses that create controversies regarding which is most appropriate in terms of clinical importance, sensitivity, reliability, and consistency. Not surprisingly, a lack of consensus exists within the scientific community regarding the optimal endpoint(s) for both acute and chronic heart failure trials. In an effort to address these issues, the Heart Failure Association of the European Society of Cardiology (HFA-ESC) convened a group of expert heart failure clinical investigators, biostatisticians, regulators, and pharmaceutical industry scientists (Nice, France, 12-13 February 2012) to evaluate the challenges of defining heart failure endpoints in clinical trials and to develop a consensus framework. This report summarizes the group's recommendations for achieving common views on heart failure endpoints in clinical trials.
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| 5. |
- Collier, T. J., et al.
(författare)
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The impact of eplerenone at different levels of risk in patients with systolic heart failure and mild symptoms: insight from a novel risk score for prognosis derived from the EMPHASIS-HF trial
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:36, s. 2823-2829
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Our objective was to create a simple prognostic risk score for patients with systolic heart failure and mild symptoms. We then assessed the efficacy of eplerenone across different categories of risk. METHODS AND RESULTS: The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF) was an international randomized trial, comparing eplerenone with placebo in 2737 patients with systolic heart failure and mild symptoms. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure, over a median 2.1 years follow-up. Using multivariable Cox modelling age, sex, systolic blood pressure, estimated glomerular filtration rate, diabetes, BMI, haemoglobin, prior heart failure (HF) hospitalization, prior myocardial infarction/coronary artery bypass surgery (CABG), and heart rate were identified as strong independent risk factors. Estimates from the model were converted into a simple integer risk score which was categorized into three groups of low-, medium-, and high risk. In placebo patients, the rates (per 100 patient-years) for the primary outcome were 7.6, 19.0, and 39.4 in the low-, medium-, and high-risk groups, respectively. On eplerenone, these rates were reduced to 5.6, 12.2, and 24.2, respectively. Eplerenone was beneficial across all risk categories and the hazard ratios were similar. The absolute treatment benefit was greatest among those at highest risk. Similar patterns emerged for all-cause mortality and for all HF hospitalizations. CONCLUSION: This easy-to-use integer risk score should be of value in quantifying individual patient risk in patients with systolic HF and mild symptoms. The relative benefits of eplerenone appeared consistent across the whole spectrum of risk, including those at lower risk.
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| 6. |
- Eapen, Z. J., et al.
(författare)
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Do Countries or Hospitals With Longer Hospital Stays for Acute Heart Failure Have Lower Readmission Rates?: Findings From ASCEND-HF
- 2013
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Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:4, s. 727-32
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Perez, A. C., et al.
(författare)
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Thyroid-Stimulating Hormone and Clinical Outcomes: The CORONA Trial (Controlled Rosuvastatin Multinational Study in Heart Failure)
- 2014
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Ingår i: JACC: Heart Failure. - : Elsevier BV. - 2213-1779. ; 2:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study sought to examine the association between thyroid status and clinical outcomes in patients in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study. Background: Hypo- and hyperthyroidism were associated with worse clinical outcomes in the SCD-HeFT (Sudden Cardiac DeathinHeart Failure Trial). Methods: In CORONA, 4,987 patients underwent baseline thyroid-stimulating hormone (TSH) measurement, 237 of which(4.8%) were receiving thyroid replacement therapy (TRT). Patients were classified as euthyroid (TSH: 0.3 to 5.0μU/ml,and no TRT), hyperthyroid (<0.3 μU/ml and no TRT), or hypothyroid (>5.0 μU/ml and no TRT). The outcome composites of cardiovascular (CV) death or hospitalization for heart failure (HF), the components of this composite, and all-cause death were compared among hyperthyroid, hypothyroid, and euthyroid states, using multivariable models adjusting for previously reported prognostic variables. Results: A total of 91.3% of patients were euthyroid, 5.0% were hypothyroid, and 3.7% were hyperthyroid. Compared with euthyroid patients, hypothyroid patients were more likely to have a history of stroke, had worse renal function andhigher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, were more likely to be treated with an antiarrhythmic drug (or have an implantable cardioverter defibrillator), and were less likely to smoke or be treated with a beta-blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. In univariate analyses, hypothyroidism was associated with an increased risk of the composite outcome of CV death or HF hospitalization (hazard ratio: 1.29; 95% confidence interval: 1.07 to 1.57; p= 0.008), as well as all-cause death (HR: 1.36; 95% confidence interval: 1.03 to 1.76; p= 0.004). However, after adjustment for other known predictors of outcome, the associations were weakened, and when NT-proBNP was added to the models, the association between hypothyroidism and all outcomes was eliminated. Conclusions: Thyroid status is not an independent predictor of outcome in heart failure with reduced ejection fraction. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310). © 2014 American College of Cardiology Foundation.
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| 8. |
- Perez-Moreno, A. C., et al.
(författare)
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Fatigue as a predictor of outcome in patients with heart failure. Analysis of CORONA (Controlled rosuvastatin multinational trial in heart failure)
- 2014
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Ingår i: JACC: Heart Failure. - : Elsevier BV. - 2213-1779. ; 2:2, s. 187-197
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to examine the relationship between fatigue and clinical outcomes, using dyspnea as a comparator, in patients with left ventricular ejection fraction (LVEF)≤35% enrolled in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study. Background: Although fatigue is a common symptom in heart failure (HF), little is known about its association with prognosis. Methods: At baseline in CORONA, fatigue "during the past few days" was measured using a 5-point exertion scale (0= none, 1= heavy exertion, 2= moderate exertion, 3= slight exertion, 4= rest); a 4-point scale was used for dyspnea (1to4 as for fatigue). Patients were grouped into 3 categories: a fatigue score 0 to 1 (n= 535), fatigue score 2(n=1,632), and fatigue score 3 to 4 (n= 1,663); and a dyspnea score of 1 (n= 292), dyspnea score of 2(n=1,695), and dyspnea score of 3 to 4 (n= 1,843). The association between fatigue and dyspnea and the composite outcome of cardiovascular (CV) death or HF hospital stay and each component separately was examined using Kaplan-Meier analysis and Cox proportional-hazard models. We also examined all-cause mortality. Results: In univariate analyses, symptom severity was associated with a higher risk of CV death or HF hospital stay (fatigue: group 3, 49% [n= 810], vs. group 1, 30% [n= 160]; dyspnea: group 3, 50% [n= 918], vs. group 1, 28% [n= 82]) and all-cause mortality (fatigue: group 3, 38% [n= 623], vs. group 1, 24% [n= 130]; dyspnea: group 3, 38% [n=697], vs. group 1, 23% [n= 66], log-rank p< 0.0001 for all). After adjusting for other prognostic variables, including LVEF, New York Heart Association class, and N-terminal pro-B-type natriuretic peptide level, worse fatigue remained associated with higher risk of HF hospital stay but not mortality (worse dyspnea remained associated with a higher risk of both). An increase in fatigue (or dyspnea) between baseline and 6 months was also associated with worse outcomes. Conclusions: In HF, greater fatigue is associated with worse clinical outcomes. Closer attention should be paid to this symptom in clinical practice, with more done to standardize its measurement and understand its origins, with a view to improving treatment. © 2014 American College of Cardiology Foundation.
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| 9. |
- Rogers, J. K., et al.
(författare)
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Eplerenone in patients with systolic heart failure and mild symptoms: analysis of repeat hospitalizations
- 2012
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Ingår i: Circulation. - 1524-4539. ; 126:19, s. 2317-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Eplerenone is known to reduce time to first hospitalization for heart failure or cardiovascular death in patients with heart failure and mild symptoms. In chronic diseases such as heart failure, characterized by repeat hospitalizations, analyzing all heart failure hospitalizations, not just the first, should give a more complete picture of treatment benefits. METHODS AND RESULTS: The Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF) trial compared eplerenone with placebo in 2737 patients with mild heart failure, followed for a median 2.08 years (interquartile range, 1.08-3.10 years). Data were collected on all hospitalizations, with a focus on those due to heart failure. Heart failure hospitalization rates in the eplerenone and placebo groups were 10.70 and 16.99 per 100 patient-years, respectively. Allowing for skewness in the frequency of hospitalizations by using the negative binomial generalized linear model, the rate ratio (eplerenone versus placebo) was 0.53 (95% confidence interval, 0.42-0.66; P<0.0001). A plot of cumulative hospitalization rates over time revealed that most of the reduced risk on eplerenone occurred in the first year of follow-up. Several baseline variables strongly predicted the risk of hospitalization. More complex statistical methods, adjusting for mortality (as informative censoring), made a negligible difference in these findings. CONCLUSIONS: Eplerenone markedly reduces the risk of heart failure hospitalizations in patients with heart failure and mild symptoms to a greater extent than is captured by only studying the time to first hospitalization. Future clinical trials in heart failure would gain from incorporating repeat hospitalizations into their primary evaluation of treatment effects. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.
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| 10. |
- Thune, J. J., et al.
(författare)
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Predictors and prognostic impact of recurrent myocardial infarction in patients with left ventricular dysfunction, heart failure, or both following a first myocardial infarction
- 2011
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Ingår i: European Journal of Heart Failure. - 1388-9842. ; 13:2, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Recurrent myocardial infarction (MI) is common after a first MI and is associated with increased morbidity and mortality. Predictors and prognosis of a recurrent MI with contemporary management are not well known. METHODS AND RESULTS: We assessed the predictors and prognostic impact of a first recurrent MI in 10 599 patients with left ventricular dysfunction, heart failure, or both following a first MI from the Valsartan in Acute Myocardial Infarction Trial (VALIANT) cohort. During a median follow-up of 27.4 months, 861 patients (9.6%) had a recurrent MI. The median time to recurrence was 136 days (quartiles 35-361 days), with a declining rate of recurrent MI within the first 3 months. The strongest predictors of recurrent MI were reduced estimated glomerular filtration rate, unstable angina, diabetes, and age. Mortality was markedly elevated (20.5%) within the first 7 days of a recurrent MI. Patients who survived 7 days after a recurrent MI continued to be at increased risk of death compared with patients without a recurrent MI and the risk of death remained elevated more than two-fold a year after the recurrent MI (adjusted hazards ratio 2.4, 95% confidence interval 1.7-3.2). One-year mortality for the entire VALIANT cohort was 10.3%, whereas 38.3% of the patients were dead 1 year after recurrent MI. Early reinfarctions (within 1 month) was associated with significantly higher 30-day mortality than later reinfarctions. CONCLUSION: Even in the context of contemporary treatment, a recurrent MI confers a significantly increased risk of death in patients following a high-risk first MI. Strategies aimed at reducing recurrent MI will thus likely prolong survival in post-MI survivors.
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