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 from the American College of Cardiology 2007: ALPHA, EVEREST, FUSION II, VALIDD, PARR-2, REMODEL, SPICE, COURAGE, COACH, REMADHE, pro-BNP for the evaluation of dyspnoea and THIS-diet

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 meeting in March 2007. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. The ALPHA study suggested that patients with heart failure (HF) due to idiopathic dilated cardiomyopathy who have a negative T-wave alternans test have a good prognosis and are unlikely to benefit from ICD therapy. EVEREST provides some evidence of short-term symptom benefit of tolvaptan in patients with acute decompensated HF but no clinically important long-term benefit. FUSION II failed to show a benefit of nesiritide in patients with chronic decompensated HF. Reducing blood pressure in hypertensive patients improved diastolic dysfunction in VALIDD. Eplerenone did not improve left ventricular remodelling in mild to moderate chronic HF. Selecting HF patients for revascularisation using FDG-PET imaging did not significantly improve outcome. Crataegus extract added to standard HF therapy did not reduce morbidity or mortality in SPICE. The COURAGE study, conducted in patients without HF or major cardiac dysfunction, showed that PCI did not reduce cardiac morbidity or mortality and can be safely deferred in patients with stable coronary disease on optimal medical therapy. The COACH study failed to show that HF nurse-intervention could reduce hospitalisations but did show trends to lower mortality, especially amongst patients with reduced ejection fraction; however, the smaller REMADHE study suggested striking benefits on morbidity and mortality. A large study of BNP provided additional information on its ability to distinguish cardiac and pulmonary breathlessness. The importance of dietary intervention in post-MI patients was highlighted by the findings of THIS-diet study.     

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.     

Clinical trials update from the American Heart Association 2007: CORONA, RethinQ, MASCOT, AF-CHF, HART, MASTER, POISE and stem cell therapy

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American Heart Association 2007. These should be considered as preliminary data, as analyses may change in the final publication. Rosuvastatin did not reduce mortality compared to placebo in patients with heart failure and left ventricular systolic dysfunction due to ischaemic heart disease in the CORONA study. Results of RethinQ provide equivocal evidence of benefit from CRT in patients with heart failure, echocardiographic dyssynchrony and QRS interval <130 ms. In the MASCOT study, the addition of atrial overdrive pacing did not reduce the incidence of permanent atrial fibrillation in patients receiving CRT. The AF-CHF study failed to show a benefit of rhythm control over rate control in patients with heart failure and atrial fibrillation. Self-management skills training and education had no benefit on the combined outcome of death or heart failure hospitalisation, compared with education alone in heart failure patients in the HART study. Microvolt T-wave alternans testing failed to identify patients at increased risk of life-threatening ventricular arrhythmias in the MASTER study. POISE suggests that initiating metoprolol therapy shortly prior to non-cardiac surgery increases the risk of hypotension, stroke and death, despite reducing the risk of myocardial infarction. Three trials of stem cell therapy in post-MI patients gave conflicting results.     

Clinical trials update from the American Heart Association meeting: ACORN-CSD, primary care trial of chronic disease management, PEACE, CREATE, SHIELD, A-HeFT, GEMINI, vitamin E meta-analysis, ESCAPE, CARP, and SCD-HeFT cost-effectiveness study

This article provides information and a commentary on landmark trials presented at the American Heart Association meeting held in November 2004, relevant to the pathophysiology, prevention, and treatment of heart failure. An open trial of the ACORN Cardiac Support Device (CSD) showed encouraging preliminary results in patients with severe heart failure. The PEACE (Prevention of Events with Angiotensin-Converting Enzyme inhibition) study supports data from previous studies showing that ACE inhibitors reduce vascular events in patients at increased risk. The CREATE (clinical trial of metabolic modulation in acute MI treatment evaluation) study of patients with acute myocardial infarction (MI) showed no mortality benefit of a glucose/insulin/potassium regimen, but treatment with reviparin reduced the incidence of death, MI, or stroke. Azimilide was not associated with a significant reduction in shocks, but reduced the shocks or episodes of markedly symptomatic ventricular tachycardia terminated by pacing in the SHIELD (Shock Inhibition Evaluation with Azimilide) study. The addition of isosorbide dinitrate plus hydralazine to standard therapy improved survival in black heart failure patients in the A-HeFT (African-American Heart Failure Trial) study. In an investigation of hypertensive patients with diabetes, carvedilol had fewer adverse effects on diabetic control than metoprolol. A meta-analysis of high-dose vitamin E supplementation suggested an association with increased mortality. The ESCAPE (Evaluation Study of CHF and Pulmonary Artery Catheterisation Effectiveness) study showed no benefit of pulmonary artery catheterisation over clinical management in patients with severe heart failure. Routine prophylactic coronary revascularisation for stable coronary disease prior to major vascular surgery showed no benefit in the CARP (Coronary Artery Revascularization Prophylaxis) study. Analysis of data from SCD-HeFT supports the cost-effectiveness of ICDs in heart failure, although overall cost implications may be prohibitive.     

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 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: 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 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 American College of Cardiology 2008: CARISMA, TRENDS, meta-analysis of Cox-2 studies, HAT, ON-TARGET, HYVET, ACCOMPLISH, MOMENTUM, PROTECT, HORIZON-HF and REVERSE

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. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. CARISMA investigated the use of implantable loop recorders for detecting life-threatening arrhythmias in patients with LVSD after MI and found that brady- and ventricular tachy-arrhythmias predicted an adverse prognosis. The TRENDS study showed that the burden of atrial fibrillation detected by pacemakers or defibrillators predicted the risk of embolic events but not with sufficient precision to justify changes in anti-thrombotic management. A meta-analysis of six trials reported an increased cardiovascular risk associated with celecoxib, particularly for heart failure, which was related to dose and baseline cardiovascular risk. The HAT study failed to show a benefit of providing post-MI patients with a home defibrillator. MOMENTUM, a study of a device designed to augment aortic blood flow, was stopped early due to increased bleeding risk. Results from PROTECT support the use of rolofylline 30 mg/day in acute heart failure, a definitive study is now underway. Istaroxime, an agent that appears to have both inotropic and lusitropic effects, improved haemodynamics when added to standard therapy in patients stabilised after admission with heart failure in HORIZON-HF. The REVERSE study suggested that CRT improves ventricular function and reduces morbidity even in patients with few or no symptoms of heart failure and may delay or prevent worsening heart failure.     

Clinical trials update from European Society of Cardiology meeting 2008: TIME‐CHF,BACH, BEAUTIFUL,GISSI‐HF,and HOME‐HF

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 meeting which was held in Munich, Germany from 30th August to 3rd September 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. The TIME‐CHF study failed to show that BNP guided therapy was superior to usual care in patients with heart failure. The BACH study suggested that a new biomarker, MR‐proANP, was as good as BNP for the diagnosis of heart failure in patients presenting with breathlessness. Ivabradine failed to reduce the incidence of cardiovascular events in patients with coronary artery disease and left ventricular systolic dysfunction in the BEAUTIFUL study, but patients with higher heart rates might have benefited. In GISSI‐HF, n–3 PUFA reduced mortality and cardiovascular hospitalisation by a small amount compared to placebo in patients with chronic heart failure, but rosuvastatin had no effect on clinical outcomes. In the HOME‐HF study, telemonitoring support failed to reduce the time to first re‐hospitalisation or death, or days alive and out of hospital, compared with usual care.     

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 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 American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty

This article provides information and a commentary on trials presented at the American Heart Association meeting held in November 2006, 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. The OAT study failed to show a benefit of PCI over optimal medical therapy in patients with persistent total occlusion of the infarct related artery following a myocardial infarction. In SALT 1 and 2, tolvaptan was found to correct hyponatraemia of various aetiologies; however, whether this has an impact on heart failure prognosis requires further evaluation. A placebo controlled study of myocardial implantation of skeletal myoblasts in patients with moderate to severe LVSD (MAGIC) showed equivocal/uncertain effects, long term follow-up data are awaited. The ABCD study which compared the ability of an invasive and a non-invasive test to identify patients at risk of arrhythmic events prior to ICD implantation, suggested that the two strategies were comparable, although the practical value of either test remains uncertain and the study had many major flaws. The PABA-CHF study hinted that pulmonary vein antrum isolation might be more effective than AV node ablation with bi-ventricular pacing for the treatment of patients with heart failure in atrial fibrillation. In IMPROVE-CHF, an NT-pro BNP guided treatment strategy was found to reduce the cost of managing patients with acute breathlessness.     

Clinical trials update from the Heart Failure Society of America and the American Heart Association meetings in 2008: SADHART-CHF,COMPARE, MOMENTUM,thyroid hormone analogue study,HF-ACTION,I-PRESERVE, β-interferon study,BACH, and ATHENA

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 and the American Heart Association meetings in 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. (i) SADHART-CHF showed no difference in outcome for heart failure patients with depression treated with sertraline compared with placebo. (ii) A controlled release carvedilol formulation showed similar LV haemodynamic effects to the standard carvedilol formulation in the COMPARE study. (iii) A post hoc analysis of the MOMENTUM study suggested that patients with less severe heart failure may be more likely to benefit from a continuous aortic flow augmentation device. (iv) A thyroid hormone analogue was poorly tolerated in patients with heart failure. (v) HF-ACTION showed that exercise training is safe and offers modest clinical benefits in patients with heart failure. (vi) Irbesartan failed to improve outcomes in patients with preserved ejection fraction in the I-PRESERVE study. (vii) A phase II study of beta-interferon administration in patients with dilated cardiomyopathy showed encouraging results. (viii) The BACH study showed that mid-regional pro-adrenomedullin was more accurate than BNP or NT-proBNP at predicting outcome at 90 days in patients with acute heart failure. (ix) A secondary analysis from ATHENA showed a reduction in cardiovascular hospitalizations and strokes for patients with atrial fibrillation receiving dronedarone compared with placebo.     

Clinical trials update from the American College of Cardiology 2009: ADMIRE‐HF,PRIMA, STICH,REVERSE, IRIS,partial ventricular support,FIX‐HF‐5, vagal stimulation,REVIVAL‐3, pre‐RELAX‐AHF,ACTIVE‐A,HF‐ACTION,JUPITER, AURORA,and OMEGA

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 meeting in 2009. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. ¹²³I‐mIBG myocardial scintigraphy was a good predictor of mortality in patients with heart failure in ADMIRE‐HF. In PRIMA, use of individualized target NT‐proBNP levels failed to improve outcomes compared with usual care in patients hospitalized with symptomatic heart failure. In the STICH trial, additional ventricular reconstruction surgery failed to improve outcomes in patients with ischaemic heart failure undergoing CABG. Cardiac resynchronization therapy may modify disease progression in patients with mild heart failure, according to data from REVERSE. Implantation of a defibrillator early after MI in high‐risk patients in the IRIS study failed to improve outcomes compared with usual care. Cardiac contractility modulation showed some beneficial effects on symptoms and exercise capacity in the unblinded FIX‐HF‐5 study. Data from pre‐RELAX‐AHF show that relaxin may have potential as a treatment for acute heart failure. HF‐ACTION showed that patients who complied with an exercise training regime achieved a better outcome, although this may be confounded by the ability of patients with a good prognosis to exercise for longer.     

Clinical trials update and cumulative meta-analyses from the American College of Cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-Lipids and cardiac resynchronisation therapy in heart failure

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the American College of Cardiology meeting, held in New Orleans, Louisiana, USA in March 2004 are reported. These new data have been added to existing data in cumulative meta-analyses. The WATCH study randomised 1587 patients with heart failure and left ventricular systolic dysfunction to warfarin, aspirin or clopidogrel. The study showed no difference between the effects of these agents on mortality or myocardial infarction, but hospitalisations for heart failure were higher on aspirin (22.2%) compared to warfarin (16.1%). The SCD-HeFT study showed that ICD therapy reduced all-cause mortality at 5 years by 23% in patients with predominantly NYHA class II heart failure and left ventricular systolic dysfunction, but amiodarone was ineffective. The DINAMIT study showed that ICD therapy was not beneficial in patients with left ventricular dysfunction after a recent MI, even in those with risk factors for arrhythmic death. In CASINO, levosimendan improved survival compared with dobutamine or placebo in patients with decompensated heart failure. INSPIRE showed that SPECT imaging can be used to assess risk early after acute MI safely and accurately. Rimonabant was shown to be safe and effective in treating the combined cardiovascular risk factors of smoking and obesity. An overview of new developments in cardiac resynchronisation therapy (CRT) in heart failure is also reported.     

Clinical trials update from the European Society of Cardiology Heart Failure meeting and the American College of Cardiology: darbepoetin alfa study, ECHOS, and ASCOT-BPLA

This article provides information and a commentary on landmark trials presented at the European Society of Cardiology Heart Failure meeting held in June 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. The erythropoiesis stimulating protein, darbepoetin alfa, increased haemoglobin levels, improved quality of life and showed a trend for improved exercise duration in anaemic patients with symptomatic chronic heart failure. In the ECHOS study, the selective dopamine agonist nolomirole (CHF1035) showed no benefit in heart failure patients. Preliminary results of the ASCOT-BPLA study, which were reported at the American College of Cardiology meeting in March 2005, showed that in hypertensive patients, treatment with a calcium antagonist plus an ACE inhibitor was more effective at reducing cardiovascular outcomes than atenolol plus a diuretic.     

Clinical trials update from the American Heart Association: REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE, and PROACTIVE

This article provides information and a commentary on trials presented at the American Heart Association meeting held in November 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 REPAIR-AMI an improvement in ejection fraction was observed in post-MI patients following infusion of bone marrow stem cells. However, the ASTAMI study showed no benefit of stem cell implantation in a similar patient cohort. The JELIS study reported a reduction in major coronary events in patients receiving statins plus fish oil compared to statins alone. MEGA showed that low dose statins in a low risk population reduce the incidence of major cardiovascular events. Two studies of levosimendan in acute heart failure gave conflicting results, in the REVIVE-II study levosimendan was reported to have a superior effect on the composite primary outcome compared to placebo, however, in SURVIVE despite a trend to early benefit with levosimendan, there was no difference in effect on long-term outcome versus dobutamine. The PROACTIVE study showed encouraging results for the use of pioglitazone in post-myocardial infarction patients with concomitant type 2 diabetes.     

Clinical trials update from Heart Rhythm 2008 and Heart Failure 2008: ATHENA, URGENT, INH study, HEART and CK-1827452

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the Heart Rhythm Society meeting in San Francisco, USA and the Heart Failure Association meeting of the European Society of Cardiology which was held in Milan, Italy in June 2008. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. The ATHENA study showed that dronedarone reduced the incidence of the composite outcome of cardiovascular hospitalisation or death, in patients with atrial fibrillation or flutter, 29% of whom had a history of heart failure, compared with placebo. The URGENT study demonstrated that treatment of acute heart failure with standard therapy, including intravenous diuretics and nitrates, leads to a rapid resolution of breathlessness in the sitting position but that orthopnoea often persists. The INH study showed that a disease management programme could reduce mortality compared to usual care but not hospitalisation rates. The HEART study failed to recruit its planned number of patients, although it is the largest randomised trial of revascularisation in heart failure reported to date. At a median follow-up of 5 years no difference in mortality was observed but the study lacked power to provide a conclusive result. The selective myosin activator CK-1827452 produced a concentration dependent increase in systolic ejection time, stroke volume and fractional shortening in patients with heart failure compared to placebo.