| 1. |
- Abrahamsson, Putte, 1965, et al.
(author)
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Impact of hospitalization for acute coronary events on subsequent mortality in patients with chronic heart failure
- 2009
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In: Eur Heart J. - 1522-9645. ; 30:3, s. 338-45
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Journal article (peer-reviewed)abstract
- AIMS: We explored the impact of having a hospital admission for an acute coronary syndrome (ACS) on the subsequent prognosis among patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 7599 patients with CHF, New York Heart Association Classes II-IV, were randomly assigned to candesartan or placebo. We assessed the risk of death after a first ACS using time-updated Cox proportional hazard models adjusted for baseline predictors. During a mean follow-up of 3.3 years, 1174 patients experienced at least one ACS. Myocardial infarction (MI) was the first ACS in 442 subjects and unstable angina (UA) in 732. After these events, 219 (49.5%) and 167 (22.8%) patients died during follow-up. The early risk of death was more pronounced after MI: 30.2% died within 30 days compared with 3.6% after UA. After an ACS event, the risk of death declined steadily over time, although 18 months after an MI the risk was still twice that of patients without an ACS. CONCLUSION: Patients with CHF, who develop an ACS, have markedly increased subsequent mortality, particularly in the early phase after an MI.
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| 2. |
- Allen, L. A., et al.
(author)
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Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program
- 2009
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In: Eur J Heart Fail. - : Wiley. - 1388-9842. ; 11:2, s. 170-7
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Journal article (peer-reviewed)abstract
- AIMS: The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated. METHODS AND RESULTS: We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long-term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P<0.0001) and all-cause mortality (HR 1.19 per 1 SD increase, P<0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi-square). CONCLUSION: Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.
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| 3. |
- Boman, K., et al.
(author)
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Effects of carvedilol or metoprolol on PAI-1, tPA-mass concentration or Von Willebrand factor in chronic heart failure - a COMET substudy
- 2009
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In: Thrombosis Research. - 1879-2472. ; 125:2, s. 46-50
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Journal article (peer-reviewed)abstract
- INTRODUCTION: In COMET (Carvedilol or Metoprolol European Trial), carvedilol reduced mortality compared with metoprolol in patients with chronic heart failure. We hypothesized that carvedilol might have greater effects on endothelial derived haemostatic factors than metoprolol. We aimed to study the effects of carvedilol or metoprolol on tissue plasminogen activator (tPA), its inhibitor PAI-1 and Von Willebrand factor (VWF) in patients with heart failure. MATERIAL AND METHODS: We recruited 260 patients (134 on carvedilol, 126 on metoprolol), mean age 66 years and 84% of them men. Plasma mass concentrations of tPA and PAI-1and percent of VWF were measured at baseline and after one and two years of treatment. RESULTS: Plasma tPA, PAI-1 and VWF were similar between treatment groups at baseline and no significant differences between groups emerged after one or two years of treatment. In paired analyses in patients assigned to carvedilol, median PAI-1 level decreased from 37.2 to 32.1 microg/l at two years (p=0.034) and of VWF decreased from baseline to one year (240 vs. 218%, p=0.023) in patients assigned to carvedilol but were not reduced at any time in patients assigned to metoprolol. Plasma tPA increased over time in both treatment groups (p=0.013 and 0.027 respectively). CONCLUSION: We found no significant difference in the effects of carvedilol or metoprolol on tPA, PAI-1 and VWF. Comparison over time within treatment groups suggested that PAI-1 and VWF might have declined on carvedilol but not on metoprolol. Our hypothesis is not proved but this may reflect an inadequate sample size rather than lack of an effect.
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| 4. |
- Cleland, J. G., et al.
(author)
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A comparison of the effects of carvedilol and metoprolol on well-being, morbidity, and mortality (the "patient journey") in patients with heart failure: a report from the Carvedilol Or Metoprolol European Trial (COMET)
- 2006
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 47:8, s. 1603-11
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Journal article (peer-reviewed)abstract
- OBJECTIVES: This study was designed to investigate the loss of well-being, in terms of life-years, overall and in patients randomized to metoprolol versus carvedilol in the Carvedilol Or Metoprolol European Trial (COMET). BACKGROUND: The ultimate objectives of treating patients with heart failure are to relieve suffering and prolong life. Although the effect of treatment on mortality is usually described in trials, the effects on patient well-being throughout the trials' courses are rarely reported. METHODS: A total of 3,029 patients randomized in the COMET study were included in the analysis. "Patient journey" was calculated by adjusting days alive and out of hospital over four years using a five-point score completed by the patient every four months, adjusted according to the need for intensification of diuretic therapy. Scores ranged from 0% (dead or hospitalized) to 100% (feeling very well). RESULTS: Over 48 months, 17% of all days were lost through death, 1% through hospitalization, 23% through impaired well-being, and 2% through the need for intensified therapy. Compared with metoprolol, carvedilol was associated with fewer days lost to death, with no increase in days lost due to impaired well-being or days in hospital. The "patient journey" score improved from a mean of 54.8% (SD 26.0) to 57.4% (SD 26.3%) (p < 0.0068). CONCLUSIONS: Despite treatment with beta-blockers, heart failure remains associated with a marked reduction in well-being and survival. Loss of quality-adjusted life-years through death and poor well-being seemed of similar magnitude over four years, and both were much larger than the loss that could be attributed to hospitalization.
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| 5. |
- Cleland, J. G., et al.
(author)
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A description of the clinical characteristics at baseline of patients recruited into the Carvedilol or Metoprolol European Trial (COMET)
- 2004
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In: Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. - 0920-3206. ; 18:2, s. 139-52
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: The COMET trial was a prospective, double-blind, randomised trial comparing carvedilol, a comprehensive adrenergic receptor antagonist, with metoprolol, a beta-1-selective agent in patients with heart failure and left ventricular systolic dysfunction. The trial showed a reduction in mortality with carvedilol that was consistent across subgroups. The purpose of this report is to describe in greater detail the heterogeneity of this population at baseline with particular reference to the impact of symptomatic severity, age and gender on patient characteristics. METHODS: A descriptive report using data entered in the COMET study data-base. RESULTS: The characteristics of the population studied were similar to those reported in previous trials of beta-blockers. Almost all patients were receiving diuretics and ACE inhibitors with few patients taking angiotensin receptor blockers. As expected, older patients had more co-morbidity. Older patients and women reported worse symptoms and poorer well-being despite similar ventricular dimensions and systolic dysfunction. NT-proBNP was higher in patients with more severe symptoms and older patients but not in women, although differences in NT-proBNP may have been confounded by differences in renal function. CONCLUSION: Age and gender, as well as the severity of cardiac dysfunction, appear to have an important effect on the severity of heart failure symptoms and patient 'well-being'. This could have important implications for the relationship between symptoms and prognosis and therefore the way in which patients are selected for clinical trials and the goals of treatment. This will be the subject of further analyses.
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| 6. |
- Cleland, J. G., et al.
(author)
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The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis
- 2003
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In: European heart journal. - 0195-668X. ; 24:5, s. 442-63
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Research review (peer-reviewed)abstract
- BACKGROUND: The European Society of Cardiology (ESC) has published guidelines for the investigation of patients with suspected heart failure and, if the diagnosis is proven, their subsequent management. Hospitalisation provides a key point of care at which time diagnosis and treatment may be refined to improve outcome for a group of patients with a high morbidity and mortality. However, little international data exists to describe the features and management of such patients. Accordingly, the EuroHeart Failure survey was conducted to ascertain if appropriate tests were being performed with which to confirm or refute a diagnosis of heart failure and how this influenced subsequent management. METHODS: The survey screened consecutive deaths and discharges during 2000-2001 predominantly from medical wards over a 6-week period in 115 hospitals from 24 countries belonging to the ESC, to identify patients with known or suspected heart failure. RESULTS: A total of 46788 deaths and discharges were screened from which 11327 (24%) patients were enrolled with suspected or confirmed heart failure. Forty-seven percent of those enrolled were women. Fifty-one percent of women and 30% of men were aged >75 years. Eighty-three percent of patients had a diagnosis of heart failure made on or prior to the index admission. Heart failure was the principal reason for admission in 40%. The great majority of patients (>90%) had had an ECG, chest X-ray, haemoglobin and electrolytes measured as recommended in ESC guidelines, but only 66% had ever had an echocardiogram. Left ventricular ejection fraction had been measured in 57% of men and 41% of women, usually by echocardiography (84%) and was <40% in 51% of men but only in 28% of women. Forty-five percent of women and 22% of men were reported to have normal left ventricular systolic function by qualitative echocardiographic assessment. A substantial proportion of patients had alternative explanations for heart failure other than left ventricular systolic or diastolic dysfunction, including valve disease. Within 12 weeks of discharge, 24% of patients had been readmitted. A total of 1408 of 10434 (13.5%) patients died between admission and 12 weeks follow-up. CONCLUSIONS: Known or suspected heart failure comprises a large proportion of admissions to medical wards and such patients are at high risk of early readmission and death. Many of the basic investigations recommended by the ESC were usually carried out, although it is not clear whether this was by design or part of a general routine for all patients being admitted regardless of diagnosis. The investigation most specific for patients with suspected heart failure (echocardiography) was performed less frequently, suggesting that the diagnosis of heart failure is still relatively neglected. Most men but a minority of women who underwent investigation of cardiac function had evidence of moderate or severe left ventricular dysfunction, the main target of current advances in the treatment of heart failure. Considerable diagnostic uncertainty remains for many patients with suspected heart failure, even after echocardiography, which must be resolved in order to target existing and new therapies and services effectively.
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| 7. |
- Connolly, S., et al.
(author)
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Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events
- 2006
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In: American heart journal. - 1097-6744. ; 151:6, s. 1187-93
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Journal article (peer-reviewed)abstract
- BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.
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| 8. |
- Dahlström, Ulf, et al.
(author)
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Adequacy of diagnosis and treatment of chronic heart failure in primary health care in Sweden
- 2009
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 11:1, s. 92-98
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Journal article (peer-reviewed)abstract
- AIMS: We performed an observational multicentre study to obtain information of the diagnostic tools and treatments currently used in patients with chronic heart failure (CHF) in primary health care (PHC) in Sweden. Data were collected from 2093 patients in 158 randomly selected PHC centres. METHODS AND RESULTS: The mean age was 79 years. The dominating aetiology of HF was hypertension and/or ischaemic heart disease. Diagnosis was based on symptoms and/or ECG and/or chest X-ray in 69% of the patients. Treatment with a renin-angiotensin system (RAS) blocker was ongoing in 74% of the patients, but only 37% had > or = 50% of the recommended target dose. In 68%, treatment with a beta-blocker (BB) was present, but only 31% had > or = 50% of the recommended target dose. Only 42% of the patients were on treatment with an RAS blocker and a BB and only 20% had > or = 50% of the recommended target dose. CONCLUSION: The diagnostic criteria for CHF according to the European Society of Cardiology were fulfilled in only approximately 30% of the patients. In addition, evidenced-based treatments to reduce morbidity and mortality were markedly underused, particularly regarding dosing. Our findings may reflect the patients' high age and the presence of important co-morbidities.
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| 9. |
- De Luca, L., et al.
(author)
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Acute heart failure syndromes: clinical scenarios and pathophysiologic targets for therapy
- 2007
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In: Heart Fail Rev. - : Springer Science and Business Media LLC. - 1382-4147 .- 1573-7322. ; 12:2, s. 97-104
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Research review (peer-reviewed)abstract
- Acute heart failure syndromes (AHFS) represent the most common discharge diagnosis in patients over age 65 years, with an exceptionally high mortality and readmission rates at 60-90 days. Recent surveys and registries have generated important information concerning the clinical characteristics of patients with AHFS and their prognosis. Most patients with AHFS present either with normal systolic blood pressure or elevated blood pressure. Patients who present with elevated systolic blood pressure usually have pulmonary congestion, a relatively preserved left ventricular ejection fraction (LVEF), are often elderly women, and their symptoms develop typically and abruptly. Patients with normal systolic blood pressure present with systemic congestion, reduced LVEF, are usually younger with a history of chronic HF, and have symptoms that develop gradually over days or weeks. In addition to the abnormal hemodynamics (increase in pulmonary capillary wedge pressure and/or decrease in cardiac output) that characterize patients with AHFS, myocardial injury, which may be related to a decrease in coronary perfusion and/or further activation of neurohormones and renal dysfunction, probably contributes to short-term and post-discharge cardiac events. Patients with AHFS also have significant cardiac and noncardiac underlying conditions that contribute to the pathogenesis of AHFS, including coronary artery disease (ischemia, hibernating myocardium, and endothelial dysfunction), hypertension, atrial fibrillation, and type 2 diabetes mellitus. Therefore, the targets of therapy for AHFS should be not only to improve symptoms and hemodynamics but also to preserve or improve renal function, prevent myocardial damage, modulate neurohumoral and inflammatory activation, and to manage other comorbidities that may cause and/or contribute to the progression of this syndrome.
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| 10. |
- De Luca, L., et al.
(author)
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Early pharmacological treatment of acute heart failure syndromes: A systematic review of clinical trials
- 2007
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In: Acute cardiac care. - 1748-2941. ; 9:1, s. 10-21
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Journal article (peer-reviewed)abstract
- Context: Acute Heart Failure Syndromes (AHFS) is a common admission diagnosis associated with high mortality and hospital readmissions. Given the mixed results of recent clinical trials, the early management of AHFS remains controversial. Objective: To review the recent evidence regarding current and investigational therapies for the early management of AHFS. Data Sources: A systematic search of peer-reviewed publications was performed on MEDLINE and EMBASE from January 1990 to August 2006. The results of unpublished or ongoing trials were obtained from presentations at national and international meetings and pharmaceutical industry releases. Bibliographies from these references were also reviewed, as were additional articles identified by content experts. Study Selection and Data Extraction: Criteria used for study selection were controlled study design, relevance to clinicians and validity based on venue of publication and power analysis. Data Synthesis: Although all current intravenous therapies for the early management of AHFS appear to improve hemodynamics, this may not always translate into short-term clinical benefit. Conclusion: The results of the trials conducted to date in AHFS have generally been disappointing. There is, therefore, an unmet need for new therapeutic approaches for the early management of AHFS that may improve the short-term and long-term outcomes.
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