| 1. |
- Abrahamsson, Putte, 1965, et al.
(författare)
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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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Ingår i: Eur Heart J. - 1522-9645. ; 30:3, s. 338-45
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Eur J Heart Fail. - : Wiley. - 1388-9842. ; 11:2, s. 170-7
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Thrombosis Research. - 1879-2472. ; 125:2, s. 46-50
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 47:8, s. 1603-11
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Tidskriftsartikel (refereegranskat)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. |
- Connolly, S., et al.
(författare)
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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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Ingår i: American heart journal. - 1097-6744. ; 151:6, s. 1187-93
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Dahlström, Ulf, et al.
(författare)
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Adequacy of diagnosis and treatment of chronic heart failure in primary health care in Sweden
- 2009
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 11:1, s. 92-98
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Tidskriftsartikel (refereegranskat)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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| 7. |
- De Luca, L., et al.
(författare)
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Acute heart failure syndromes: clinical scenarios and pathophysiologic targets for therapy
- 2007
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Ingår i: Heart Fail Rev. - : Springer Science and Business Media LLC. - 1382-4147 .- 1573-7322. ; 12:2, s. 97-104
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Forskningsöversikt (refereegranskat)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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| 8. |
- De Luca, L., et al.
(författare)
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Early pharmacological treatment of acute heart failure syndromes: A systematic review of clinical trials
- 2007
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Ingår i: Acute cardiac care. - 1748-2941. ; 9:1, s. 10-21
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Demers, C., et al.
(författare)
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Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure
- 2005
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Ingår i: JAMA. - 1538-3598. ; 294:14, s. 1794-8
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of myocardial infarction (MI), but it is not known whether angiotensin receptor blockers have the same effect. OBJECTIVE: To assess the impact of the angiotensin receptor blocker candesartan on MI and other coronary events in patients with heart failure. DESIGN, SETTING, AND PARTICIPANTS: The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, a randomized, placebo-controlled study enrolling patients (mean age, 66 [SD, 11] years) with New York Heart Association class II to IV symptoms who were randomly allocated to receive candesartan (target dose, 32 mg once daily) or matching placebo given in addition to optimal therapy for heart failure. Patients were enrolled from March 1999 through March 2001. Of 7599 patients allocated, 4004 (53%) had experienced a previous MI, and 1808 (24%) currently had angina. At baseline, 3125 (41%) were receiving an ACE inhibitor; 4203 (55%), a beta-blocker; 3153 (42%), a lipid-lowering drug; 4246 (56%), aspirin; and 6286 (83%), a diuretic. MAIN OUTCOME MEASURE: The primary outcome of the present analysis was the composite of cardiovascular death or nonfatal MI in patients with heart failure receiving candesartan or placebo. RESULTS: During the median follow-up of 37.7 months, the primary outcome of cardiovascular death or nonfatal MI was significantly reduced in the candesartan group (775 patients [20.4%]) vs the placebo group (868 [22.9%]) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004; number needed to treat [NNT], 40). Nonfatal MI alone was also significantly reduced in the candesartan group (116 [3.1%]) vs the placebo group (148 [3.9%]) (HR, 0.77; 95% CI, 0.60-0.98; P = .03; NNT, 118). The secondary outcome of fatal MI, sudden death, or nonfatal MI was significantly reduced with candesartan (459 [12.1%]) vs placebo (522 [13.8%]) (HR, 0.86; 95% CI, 0.75-0.97; P = .02; NNT, 59). Risk reductions in cardiovascular death or nonfatal MI were similar across predetermined subgroups and the component CHARM trials. There was no impact on hospitalizations for unstable angina or coronary revascularization procedures with candesartan. CONCLUSION: In patients with heart failure, candesartan significantly reduces the risk of the composite outcome of cardiovascular death or nonfatal MI.
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| 10. |
- Desai, A. S., et al.
(författare)
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Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program
- 2007
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Ingår i: J Am Coll Cardiol. - 1558-3597. ; 50:20, s. 1959-66
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We explored the incidence and predictors of hyperkalemia in a broad population of heart failure patients. BACKGROUND: When used in optimal doses to treat patients with heart failure, renin-angiotensin-aldosterone system (RAAS) inhibitors improve clinical outcomes but can cause hyperkalemia. METHODS: Participants in the CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) (n = 7,599) Program were randomized to standard heart failure therapy plus candesartan or placebo, titrated as tolerated to a target of 32 mg once daily with recommended monitoring of serum potassium and creatinine. We assessed the incidence and predictors of hyperkalemia associated with dose reduction, study drug discontinuation, hospitalization, or death over the median 3.2 years of follow-up. RESULTS: Independent of treatment assignment, the risk of hyperkalemia increased with age > or =75 years, male gender, diabetes, creatinine > or =2.0 mg/dl, K+ > or =5.0 mmol/l, and background use of angiotensin-converting enzyme inhibitors or spironolactone. Candesartan increased the rate of aggregate hyperkalemia from 1.8% to 5.2% (difference 3.4%, p < 0.0001) and serious hyperkalemia (associated with death or hospitalization) from 1.1% to 1.8% (difference 0.7%, p < 0.001), with hyperkalemia associated with death reported in 2 (0.05%) candesartan patients and 1 (0.03%) placebo patient. The benefit of candesartan in reducing cardiovascular death or heart failure hospitalization (relative risk reduction 16%, p < 0.0001) was uniform in these subgroups, as was the incremental risk of hyperkalemia. CONCLUSIONS: The risk of hyperkalemia is increased in symptomatic heart failure patients with advanced age, male gender, baseline hyperkalemia, renal failure, diabetes, or combined RAAS blockade. Although these groups derive incremental clinical benefit from candesartan, careful surveillance of serum potassium and creatinine is particularly important.
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