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Metabolic modulation in heart failure: high time for a definitive clinical trial
  1. Houman Ashrafian,
  2. Stefan Neubauer
  1. Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
  1. Correspondence to Professor Stefan Neubauer, Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; stefan.neubauer{at}

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In developed countries the prevalence of heart failure (HF) is approximately 2% rising to approximately 10% in those greater than 70 years of age. Systolic HF, occurring in more than half of all HF patients, is a major cause of morbidity and mortality and, in the USA, constitutes Medicare's biggest expenditure (driven by inpatient care) at an annual cost in excess of US$39.2 billion. The standard of care has been influenced by three decades of randomised trials extolling the benefits of lifestyle modification, pharmacological therapies (ACE inhibitors, angiotensin receptor blockers, β-blockers, spironolactone and hydralazine–isosorbide dinitrate), implantable devices and, in a minority of cases, surgery. The success of these therapies is exemplified by the observation that HF mortality has declined by approximately a third from the 1950s to the 1990s. Despite this success, mortality rates for HF are approximately 20% and 40–54% at 1 year and 5 years, respectively.1 The persisting human and financial cost attributable to HF and the disappointing results of trials with drugs modulating promising pathways (eg, endothelin receptor blockers and anti-tumour necrosis factor therapy) mandates the identification of novel pathways and strategies for its treatment.

The putative role for myocardial energetic deficiency in the pathogenesis of HF,2 and the consequent rationale for treating this energy deficiency clinically by metabolic modulation using 3-ketoacyl coenzyme A thiolase inhibition (eg, trimetazidine), late sodium current inhibition (eg, ranolazine) and carnitine palmitoyl transferase inhibition (eg, perhexiline) is increasingly recognised.3 In their article published in this issue …

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  • Linked articles 208751.

  • Funding The authors acknowledge funding by the British Heart Foundation and the NIHR Oxford Biomedical Research Centre.

  • Competing interests HA has in partnership successfully applied for method of use patents for the use of perhexiline in heart failure and cardiomyopathies.

  • Provenance and peer review Commissioned; externally peer reviewed.

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