Rationale and design of the phase 2b clinical trials to study the effects of the partial adenosine A1-receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced (PANTHEON) and preserved (PANACHE) ejection fraction

European Journal of Heart Failure
Adriaan A VoorsScott D Solomon

Abstract

Despite major advances in the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF), morbidity and mortality associated with the condition remain high, suggesting the need for additional treatment options, particularly haemodynamically neutral treatments that do not alter blood pressure, heart rate, or renal function. HF with preserved ejection fraction (HFpEF) is also associated with high morbidity and mortality and adequate treatment options are limited; thus there is a critical unmet need for the development of novel therapies for HFpEF. Chronic HFrEF and HFpEF are both systemic disorders that affect not only the heart but several other tissues and organs including skeletal muscle, leading to exercise intolerance and dyspnoea. Partial adenosine A1-receptor agonists represent a novel potential therapy for HF regardless of underlying ejection fraction given their minimal effect on heart rate and blood pressure, and preclinical data demonstrate several possible beneficial mechanisms, including improved mitochondrial function and sarcoplasmic reticulum Ca2+ -ATPase (SERCA2a) activity, enhanced energy substrate utilization, reverse ventricular remodelling, and anti-ischemic, cardioprotective properties. H...Continue Reading

References

Oct 12, 2010·The New England Journal of Medicine·Barry M MassieUNKNOWN PROTECT Investigators and Committees
Dec 25, 2015·Heart Failure Reviews·Stephen J GreeneMihai Gheorghiade
Oct 23, 2016·Handbook of Experimental Pharmacology·Wilfried DinhHani N Sabbah
Nov 4, 2017·Journal of the American College of Cardiology·Franz H MesserliMatthias Wilhelm

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Citations

Jul 6, 2019·Journal of Cardiovascular Pharmacology·Aldo BonaventuraAntonio Abbate
Aug 22, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Bernhard Wernly, Zhichao Zhou 周稚超
Nov 21, 2019·European Journal of Heart Failure·Marianna AdamoMarco Metra
Nov 22, 2019·Frontiers in Physiology·Domenico D'AmarioFilippo Crea
Apr 12, 2019·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Allison B ReissJoshua DeLeon
Jan 28, 2020·Heart Failure Reviews·Ampadu O JacksonKai Yin
Apr 3, 2020·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·Jan WintrichMichael Böhm
Oct 2, 2021·European Heart Journal. Quality of Care & Clinical Outcomes·Yvonne Mei Fong LimStefan Koudstaal

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