Pharmacology of heart failure: From basic science to novel therapies

Pharmacol Ther. 2016 Oct:166:136-49. doi: 10.1016/j.pharmthera.2016.07.004. Epub 2016 Jul 25.

Abstract

Chronic heart failure is one of the leading causes for hospitalization in the United States and Europe, and is accompanied by high mortality. Current pharmacological therapy of chronic heart failure with reduced ejection fraction is largely based on compounds that inhibit the detrimental action of the adrenergic and the renin-angiotensin-aldosterone systems on the heart. More than one decade after spironolactone, two novel therapeutic principles have been added to the very recently released guidelines on heart failure therapy: the HCN-channel inhibitor ivabradine and the combined angiotensin and neprilysin inhibitor valsartan/sacubitril. New compounds that are in phase II or III clinical evaluation include novel non-steroidal mineralocorticoid receptor antagonists, guanylate cyclase activators or myosine activators. A variety of novel candidate targets have been identified and the availability of gene transfer has just begun to accelerate translation from basic science to clinical application. This review provides an overview of current pharmacology and pharmacotherapy in chronic heart failure at three stages: the updated clinical guidelines of the American Heart Association and the European Society of Cardiology, new drugs which are in clinical development, and finally innovative drug targets and their mechanisms in heart failure which are emerging from preclinical studies will be discussed.

Keywords: Angiotensin receptor and neprilysin inhibitor; Epigenetics; Heart failure; Ivabradine; Mineralocorticoid receptor; Omecamtiv mecarbil.

Publication types

  • Review

MeSH terms

  • Aminobutyrates / pharmacology
  • Angiotensin Receptor Antagonists / pharmacology
  • Benzazepines / pharmacology
  • Biphenyl Compounds
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / pharmacology*
  • Cardiovascular Agents / therapeutic use*
  • Chronic Disease
  • Clinical Trials as Topic
  • Drug Combinations
  • Guanylate Cyclase / biosynthesis
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology*
  • Humans
  • Ivabradine
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Myosins / biosynthesis
  • Neprilysin / antagonists & inhibitors
  • Practice Guidelines as Topic
  • Renin-Angiotensin System
  • Tetrazoles / pharmacology
  • Valsartan

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Benzazepines
  • Biphenyl Compounds
  • Cardiovascular Agents
  • Drug Combinations
  • Mineralocorticoid Receptor Antagonists
  • Tetrazoles
  • Ivabradine
  • Valsartan
  • Neprilysin
  • Myosins
  • Guanylate Cyclase
  • sacubitril and valsartan sodium hydrate drug combination