Titration and Tolerability of Sacubitril/Valsartan for Patients With Heart Failure in Clinical Practice

J Cardiovasc Pharmacol. 2019 Mar;73(3):149-154. doi: 10.1097/FJC.0000000000000643.

Abstract

Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class ≥II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patients' medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aminobutyrates / administration & dosage*
  • Aminobutyrates / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage*
  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Neprilysin / antagonists & inhibitors
  • Protease Inhibitors / administration & dosage*
  • Protease Inhibitors / adverse effects
  • Retrospective Studies
  • Tertiary Care Centers
  • Tetrazoles / administration & dosage*
  • Tetrazoles / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

  • Aminobutyrates
  • Angiotensin II Type 1 Receptor Blockers
  • Protease Inhibitors
  • Tetrazoles
  • Neprilysin
  • sacubitril-valsartan