A Review of New Pharmacologic Treatments for Patients With Chronic Heart Failure With Reduced Ejection Fraction

J Clin Pharmacol. 2016 Aug;56(8):936-47. doi: 10.1002/jcph.677. Epub 2015 Dec 30.


Heart failure (HF) impacts an estimated 5.7 million Americans, and its prevalence is projected to increase to more than 8 million Americans in the next 15 years. Key clinical trials have established an evidence-based foundation for treatment of heart failure with reduced ejection fraction (HFrEF). Ivabradine and sacubitril/valsartan, which inhibit the f-channel and the angiotensin receptor and neprilysin, respectively, were recently approved by the Food and Drug Administration for HFrEF. In systolic heart failure, treatment with the If inhibitor ivabradine significantly reduced the combined endpoint of cardiovascular mortality or heart failure hospital admission vs placebo (P < .05). In the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with angiotensin-converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure trial, sacubitril/valsartan significantly reduced the combined endpoint of cardiovascular death or heart failure hospitalization vs enalapril (P < .001). The place of therapy with ivabradine and sacubitril/valsartan is defined by these trials and their interplay with guideline-directed medical therapy. Ivabradine and sacubitril/valsartan increase pharmacotherapy options for the treatment of HFrEF but are not yet first-line agents. Clinical application will be better defined in the coming years as practitioners increase their familiarity with ivabradine and sacubitril/valsartan.

Keywords: f-channel inhibitor; heart failure with reduced ejection fraction; ivabradine; neprilysin inhibitor; sacubitril; valsartan.

Publication types

  • Review

MeSH terms

  • Aminobutyrates / pharmacology
  • Aminobutyrates / therapeutic use*
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Benzazepines / pharmacology
  • Benzazepines / therapeutic use*
  • Cardiovascular Agents / pharmacology
  • Cardiovascular Agents / therapeutic use
  • Chronic Disease
  • Clinical Trials as Topic / methods
  • Drug Combinations
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology*
  • Humans
  • Ivabradine
  • Neprilysin / antagonists & inhibitors
  • Prospective Studies
  • Stroke Volume / drug effects
  • Stroke Volume / physiology*
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use*
  • Treatment Outcome


  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzazepines
  • Cardiovascular Agents
  • Drug Combinations
  • Tetrazoles
  • Ivabradine
  • Neprilysin
  • sacubitril-valsartan