Clinical trials update from the European Society of Cardiology heart failure meeting: TNT subgroup analysis, darbepoetin alfa, FERRIC-HF and KW-3902

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the European Society of Cardiology heart failure meeting held in June 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. In a sub-group analysis of the TNT study, intensive treatment with high-dose atorvastatin significantly reduced hospitalisations for heart failure in patients with stable coronary heart disease, compared with low-dose atorvastatin; this benefit was most evident in patients with a history of heart failure at baseline. In a combined analysis of two studies of darbepoetin alfa, which included 475 patients, treatment increased and maintained haemoglobin levels and produced non-significant improvements in symptoms and morbidity in anaemic heart failure patients compared to placebo. In the FERRIC-HF study (n=35), intravenous iron sucrose therapy improved exercise capacity and symptom status in iron-deficient heart failure patients. In a combined analysis of two studies (n=186), the adenosine A(1) receptor antagonist KW-3902 showed diuretic properties and appeared to enhance response to loop diuretics in heart failure patients hospitalised with fluid overload.     

Clinical trials update from the European Society of Cardiology Heart Failure meeting: COMET,COMPANION, Tezosentan and SHAPE

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the European Society of Cardiology Heart Failure Update meeting, held in Strasbourg, France are described. The COMET study showed a 17% relative risk reduction in all-cause mortality with carvedilol compared with metoprolol tartrate. The COMPANION study, as previously reported, showed encouraging results for the use of cardiac resynchronisation and implantable defibrillator therapy in patients with heart failure, but further evidence is awaited. The results of a study on tezosentan suggest that lower doses of this endothelin antagonist may be clinically more effective with fewer adverse effects compared with higher doses. The SHAPE survey of heart failure awareness in Europe identified a need for further heart failure education amongst the public, patients, their carers and primary care physicians.     

Clinical trials update from the American College of Cardiology: Darbepoetin alfa, ASTEROID, UNIVERSE, paediatric carvedilol, UNLOAD and ICELAND

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American College of Cardiology 55th Annual Scientific Session held in March 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. Darbepoetin alfa increased haemoglobin levels in heart failure patients and improved some aspects of quality of life compared to placebo. In the ASTEROID study rosuvastatin significantly reduced LDL-cholesterol levels and induced regression of atherosclerosis in patients with CAD. Rosuvastatin also produced a significant reduction in LDL-cholesterol levels in heart failure patients in the UNIVERSE study, but had no effect on left ventricular remodelling compared to placebo. The paediatric carvedilol study failed to show a benefit of carvedilol in children with heart failure. Ultrafiltration produced a greater weight and fluid loss than intravenous diuretics in heart failure patients with volume overload in the UNLOAD study but did not exert a greater improvement in breathlessness; however, ultrafiltration did reduce readmission rates. The ICELAND MI study showed that CMR imaging was more sensitive than ECG or clinical criteria for detecting myocardial infarction.     

Clinical trials update from the joint European Society and World Congress of Cardiology meeting: PEP-CHF, ACCLAIM and the HHH study

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the joint European Society and World Congress of Cardiology meeting held in Barcelona in September 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. The PEP-CHF study suggests that perindopril improves symptoms and functional capacity and may reduce heart failure hospitalisations in patients with diastolic heart failure. Although immune modulation therapy failed to reduce the incidence of all-cause mortality and cardiovascular hospitalisations in the ACCLAIM study, the observed differences in outcome in some heart failure patients warrants further investigation. The HHH study failed to show a beneficial effect of telemonitoring over usual care in patients with heart failure but potentially important country interactions were observed.     

Clinical trials update from the European Society of Cardiology Heart Failure meeting 2011: TEHAF, WHICH, CARVIVA, and atrial fibrillation in GISSI-HF and EMPHASIS-HF

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the European Society of Cardiology Heart Failure meeting held in Gothenburg, Sweden in May 2011. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. In the TEHAF study, use of the Health Buddy^® monitoring system failed to reduce the number of HF admissions compared with usual care but a subgroup of patients with more recently diagnosed HF may have benefited. In the WHICH study, some reductions in the rate of hospital stay were observed in patients who underwent a nurse‐led home‐based intervention programme following a hospital admission for an acute HF exacerbation, compared with patients who were followed in a specialized outpatient clinic. Results from CARVIVA‐HF suggest that ivabradine alone or in combination with carvedilol is safe and effective for improving exercise capacity and quality of life in HF patients on optimized angiotensin‐converting enzyme inhibitor therapy. In the GISSI‐HF study there was no difference in atrial fibrillation (AF) occurrence between the n‐3 polyunsaturated fatty acids and placebo groups. In EMPHASIS‐HF the incidence of new onset AF or flutter was reduced in patients with mild HF randomized to eplerenone compared with placebo.     

Clinical trials update from the Heart Failure Society of America meeting: FIX-CHF-4, selective cardiac myosin activator and OPT-CHF

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the Heart Failure Society of America meeting held in Seattle in September 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. Devices designed to improve cardiac contractility may have improved exercise tolerance and quality of life in the FIX-CHF-4 study; however, uncertainties in trial interpretation exist. The results of a study reporting the first administration of the selective myosin activator CK-1827452 to human volunteers, support the initiation of clinical trials in heart failure patients. In OPT-CHF, oxypurinol failed to show benefit compared to placebo for the treatment of heart failure, although a retrospective subgroup analysis suggests that it may be beneficial in patients with elevated serum uric acid levels.     

Clinical trials update from the European Society of Cardiology Heart Failure meeting: SHAPE, BRING-UP 2 VAS, COLA II, FOSIDIAL, BETACAR, CASINO and meta-analysis of cardiac resynchronisation therapy

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the European Society of Cardiology Heart Failure Update meeting, held in Wroclaw, Poland, in June 2004 are reported. The SHAPE study identified a need to educate general practitioners (GPs) in order to optimise treatment of heart failure in primary care. BRING-UP 2 VAS showed that cognitive impairment is very common in elderly heart failure patients and that these patients require specialist care. Carvedilol was shown to be well tolerated and effective in elderly heart failure patients in the observational COLA II study. In the FOSIDIAL study of patients with end-stage renal disease, fosinopril showed no benefit over placebo in reducing the incidence of cardiovascular events in these high-risk patients. The BETACAR study showed that carvedilol and metoprolol produced a similar effect on left ventricular ejection fraction (+13.1% and +12.0%, respectively). Revised mortality data for the CASINO study and a meta-analysis of the effects of cardiac resynchronisation therapy on mortality in the light of the recently published COMPANION study are reported.     

Clinical trials update from the European Society of Cardiology: SENIORS, ACES, PROVE-IT, ACTION, and the HF-ACTION trial

This article provides information and a commentary on landmark trials presented at the European Society of Cardiology Congress in August 2004, relevant to the pathophysiology, prevention or treatment of heart failure. The SENIORS trial suggests that nebivolol is well tolerated and effective in older patients with heart failure, even if left ventricular systolic function is not markedly depressed. However, patients aged >75 years appeared to gain less benefit. Further data on the effects of nebivolol on symptoms and quality of life are awaited. Two new trials of long-term antibiotic prophylaxis after myocardial infarction (ACES and PROVE-IT) showed no benefit. The ACTION trial showed no reduction in serious cardiovascular events with nifedipine GITS in patients with chronic stable angina, despite a substantial reduction in blood pressure. The HF-ACTION trial announced that the first 700 patients of a projected 3000 had been randomised to either an exercise program or encouragement to exercise but without a formal program. The primary outcome measure is death or hospitalisation for any reason.     

Clinical trials update: Highlights of the Scientific Sessions of Heart Failure 2001, a meeting of the Working Group on Heart Failure of the European Society of Cardiology. CONTAK-CD, CHRISTMAS, OPTIME-CHF

This article continues a series of reports summarising recent research developments pertinent to the topic of heart failure. This is a summary of presentations made at Scientific Sessions of Heart Failure 2001, a meeting of the Working Group on Heart Failure of the European Society of Cardiology. Clinical studies of particular interest to people caring for patients with heart failure include CONTAK-CD, CHRISTMAS and further updates on OPTIME-CHF. A brief review of the current status of cardiac resynchronisation therapy is included.     

Clinical trials update from the European Society of Cardiology: CHARM, BASEL, EUROPA and ESTEEM

This article contains a series of reports on recent research developments in the field of heart failure. Reports of key presentations made at the European Society of Cardiology meeting, held in Vienna, Austria, between 30 August and 3 September 2003 are reported. In the CHARM study, candesartan reduced cardiovascular deaths and hospital admissions for heart failure, both in patients who were already taking an ACE-inhibitor and in those who were ACE intolerant. However, results in patients with preserved left ventricular function were less conclusive. The BASEL study supports the use of B-type natriuretic peptide testing to confirm the diagnosis of heart failure in patients presenting with acute dyspnoea. In EUROPA, the largest ever study of secondary prevention of coronary artery disease, long-term treatment with perindopril reduced the incidence of cardiovascular death, myocardial infarction (MI) and cardiac arrest. The ESTEEM study showed that the oral thrombin inhibitor ximelagatran plus aspirin was more effective than aspirin alone in the prophylaxis of major cardiovascular events following MI.     

Clinical trials update from the Heart Failure Society of America: EMOTE, HERB-CHF, BEST genetic sub-study and RHYTHM-ICD

This article summarises key presentations relevant to the pathophysiology, prevention or treatment of heart failure, from the Heart Failure Society of America annual meeting held in Toronto, Canada. Data from the EnoxiMone in intravenous inOTropE-dependent subjects (EMOTE) study suggest that the oral PDE-3 inhibitor enoximone may be effective for weaning severe heart failure patients from intravenous inotropic therapy. Hawthorn Extract Randomised Blinded Trial in CHF (HERB-CHF) failed to show a benefit of hawthorn extract added to conventional heart failure therapy. A genetic sub-group analysis of the Blocker Evaluation of Survival Trial (BEST) study showed that bucindolol reduced mortality and hospitalisations in patients who were homozygous for the Arg389 variant of the beta(1) adrenoceptor. In the Resynchronisation Hemodynamic Treatment for Heart Failure Management (RHYTHM-ICD) study, patients randomised to cardiac resynchronisation therapy (CRT) showed an improvement in symptoms and functional capacity compared to the control group.     

Update of clinical trials from the American College of Cardiology 2003. EPHESUS,SPORTIF-III,ASCOT, COMPANION,UK-PACE and T-wave alternans

The American College of Cardiology provided much useful new information to inform those who care for patients with heart failure about what they should and should not adopt into current clinical practice. The EPHESUS trial suggests a much wider role for aldosterone antagonists for the management of heart failure and left ventricular systolic dysfunction. SPORTIF-III indicates we may have a safer, simpler warfarin substitute soon. ASCOT reinforces the potential futility of statin therapy unless it is well targeted. The results of the COMPANION study investigating cardiac resynchronisation devices and implantable defibrillators were encouraging but inconclusive and/or hard to interpret. UK-PACE again questions the use of dual chamber pacing. T-wave alternans is an interesting experimental technique that may be useful in selecting which patients need an implantable defibrillator, although the technology needs testing in an appropriate patient population.     

Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE

This article provides information and a commentary on trials presented at the European Society of Cardiology meeting held in September 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. In the CARE-HF extension study, the benefits of cardiac resynchronisation therapy (CRT) observed in the original study were maintained over an increased follow-up period. A study of oral enoximone (25-50 mg t.i.d.) in advanced heart failure (ESSENTIAL) showed limited benefit compared to placebo. The CIBIS-III study showed that heart failure therapy could be safely initiated with bisoprolol followed by the addition of enalapril. A subcutaneous ICD system (S-ICD) showed potential as an alternative to a transvenous ICD. In the ISSUE-2 study, an implantable loop recorder was used to guide therapy in patients with recurrent syncope. The selective endothelin antagonist sitaxsentan improved 6-MWT and functional class in patients with pulmonary arterial hypertension in the STRIDE-2 study. In SOFA, fish oil had no beneficial effect on the incidence of life-threatening arrhythmias in patients with an ICD. In IMAGINE, quinapril showed no benefit when administered to patients following CABG. Perindopril reduced cardiac remodelling in post-MI patients with normal LV function in PREAMI. SIRIUS-II showed encouraging results for the use of intravenous ularitide in symptomatic decompensated chronic heart failure. The ACTIVE W study of warfarin versus aspirin plus clopidogrel in atrial fibrillation has been stopped due to superiority of warfarin.     

Clinical trials update from the European Society of Cardiology: CARMEN,EARTH, OPTIMAAL,ACE, TEN-HMS,MAGIC, SOLVD-X and PATH-CHF II

This article continues a series of reports on research developments related to the field of heart failure. Reports of presentations made at the Hot Line sessions of the European Society of Cardiology XXIV Congress held in Berlin, Germany, between 31 August and 4 September 2002 are included. Summaries of the results of the following trials are presented: CARMEN, EARTH, OPTIMAAL, ACE, TEN-HMS, MAGIC, SOLVD-X and PATH-CHF II.     

Clinical trials update from the European Society of Cardiology Meeting 2010: SHIFT, PEARL-HF, STAR-heart, and HEBE-III

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the annual meeting of the European Society of Cardiology held in Stockholm in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The SHIFT study supports the use of ivabradine in patients with HF due to left ventricular systolic dysfunction and resting sinus rhythm rate ≥70 b.p.m. despite treatment with beta-blockers or where beta-blockers are contra-indicated. Results from PEARL-HF suggest that the potassium binding polymer RLY5016 may be useful for both prevention and treatment of hyperkalaemia in HF patients with or without concomitant chronic kidney disease. The STAR-heart study provides encouraging observational data about the potential for intracoronary stem cell transplantation in patients with HF. Results from HEBE-III showed no effect of erythropoietin on ejection fraction measured 6 weeks post-MI; although there were fewer cardiovascular events in patients assigned to erythropoietin, the study was too small to provide conclusive evidence of effect.