Results of both late breaking trials presented at Heart Failure 2013
Lisbon – Ambulatory levosimendan improves event free survival by 50% compared to placebo, according to results from the LevoRep Study presented today during the late breaking trial session (1) of the Heart Failure Congress 2013. In a second study, the third generation mineralocorticoid receptor antagonist (MRA) BAY 94-8862 showed improved potassium and kidney tolerance in heart failure patients with chronic kidney disease (CKD).
Heart Failure 2013 is the main annual meeting of the Heart Failure Association of the European Society of Cardiology and is being held 25-28 May in Lisbon, Portugal (2).
The prevalence of end-stage heart failure is increasing significantly and is associated with frequent hospital admissions and high costs. LevoRep is the largest trial of repetitive ambulatory administration of an inotrope in end-stage heart failure. The study focused on the safety and efficacy of levosimendan in an ambulatory setting.
LevoRep was a multicentre study in which 120 patients with end-stage heart failure were randomised to receive biweekly 0.2 mcg/kg/min levosimendan for 6 hours over 6 weeks or placebo. The study met its secondary endpoints and showed that ambulatory levosimendan was safe and improved event free survival by 50% compared with placebo. However, the study failed to show significant improvements in functional capacity and quality of life which were the primary endpoints.
Presenter Dr Gerhard Poelzl (Austria) said: “Future studies with more patients and higher dosing or higher repetition frequencies of levosimendan in an outpatient setting could show positive results for the primary endpoints. The improvement in event-free survival shown in this study may revive an old concept of ambulatory treatment of end-stage heart failure patients which has been largely dismissed because of the excessive mortality with intropes.”
The MinerAlocorticoid Receptor Antagonist Tolerability Study (ARTS) was a randomised, double blind, phase 2 trial of BAY 94-8862 in patients with chronic heart failure and mild/moderate chronic kidney disease. First (spironolactone) and second (eplerenone) generation MRAs have safety issues including risk of hyperkalemia and worsened renal function. Their use is limited in patients with poor renal function, a frequent comorbidity in patients with heart failure.
The fourth generation MRA BAY 94-8862 is non-steroidal and BAY 94-8862 is thought to be more kidney friendly. This is due to its pharmacokinetics of distribution where the drug tends to be compartmentalised to a greater extent in the heart than the kidneys when compared to spironolactone and eplerenone in rodents, suggesting targeted action on the cardiovascular system with fewer effects on the kidney.
Part B of the ARTS trial, presented today, randomised 393 patients with heart failure and moderate CKD to BAY 94-8862 (2.5, 5, or 10mg once daily or 5mg twice daily), placebo or the standard dose of spironolactone.
All BAY 94-8862 doses were safe and well tolerated and BAY 94-8862 was associated with less hyperkalemia and better kidney tolerance than spironolactone. Both drugs produced an almost equal effect on brain natriuretic peptide (BNP), a hemodynamic biomarker of remodelling of the heart.
Presenter Professor Faiez Zannad (France) said: “This fourth generation drug is better tolerated when it comes to potassium and the kidney even in patients at higher risk because of pre-existing moderate CKD. There is a real unmet need in this population because while MRAs are not contraindicated, many doctors are wary of using them because of the side effects in the kidney. This study is the first important step towards investigating newer and wider indications for MRAs.”
He concluded: “Future studies will investigate BAY 94-8862 novel indications: patients with heart failure and either moderate CKD or diabetes hospitalized for worsening chronic heart failure, and kidney protection in diabetics.”
Link to session on the Scientific Programme Online
1. Monday’s late breaking trial session included the following abstracts: Link to session on the Scientific Programme Online.
Efficacy and safety of intermittent ambulatory infusions of Levosimendan in end-stage heart failure (LevoRep). G. Poelzl
MinerAlocorticoid Receptor Antagonist Tolerability Study ARTS: a randomized, double-blind, phase 2 trial of BAY 94-8862 in patients with chronic heart failure and mild/moderate chronic kidney disease. F. Zannad
Additive renin inhibition with Aliskiren does not improve renal blood flow and decreases glomerular filtration rate and filtration fraction in patients with chronic heart failure and renal dysfunction. H. Hillege
Effect of Aliskiren on postdischarge mortality and readmissions among patients hospitalised for heart failure. M. Gheorghiade
The dopamine in acute decompensated heart failure II trial. G. Giamouzis
Aggressive fluid and sodium restriction in acute decompensated heart failure. L. Beck da Silva
2. Heart Failure 2013
ESC Press Office
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About the European Society of Cardiology (ESC)
The European Society of Cardiology (ESC) represents more than 80,000 cardiology professionals across Europe and the Mediterranean. Its mission is to reduce the burden of cardiovascular disease in Europe.
About the Heart Failure Association (HFA)
The Heart Failure Association (HFA) is a registered branch of the ESC. Its aim is to improve quality of life and longevity, through better prevention, diagnosis and treatment of heart failure, including the establishment of networks for its management, education and research.
For practical information about heart failure aimed at patients, families and caregivers, visit the HFA’s Heart Failure Matters website.
About press registration
On-site registration opens 25 May 2013 in Lisbon supported by presentation of a press card or letter of assignment with proof of 3 published articles together with the filled in and signed embargo form 2013.