Chronic heart failure with reduced ejection fraction

Research Review E-Learning Module

Begin

Chronic heart failure with reduced ejection fraction

This Research Review E-Learning Module is intended for New Zealand pharmacists and covers the use of angiotensin receptor neprilysin inhibitors (ARNIs) in heart failure with reduced ejection fraction. It is based on the Research Review Product Review of sacubitril/valsartan (Entresto®).


Before starting the module please read the Research Review Product Review publication, accessed through the link below:

Sacubitril/valsartan (Entresto®) Product Review

The PDF can be viewed on screen, saved and printed through the link above. 

This E-Learning Module covers:

  • Heart failure epidemiology & burden of disease
  • Angiotensin receptor neprilysin inhibitors (ARNIs)
  • Mechanism of action of ARNIs
  • Indications and funding for sacubitril/valsartan
  • Pharmacological properties of sacubitril/valsartan
  • Efficacy & safety of sacubitril/valsartan
  • Patient selection for sacubitril/valsartan
  • Dosing & titration of sacubitril/valsartan

Learning outcomes

After completing this module you should have an improved understanding of:

  • Heart failure epidemiology & burden of disease
  • Angiotensin receptor neprilysin inhibitors (ARNIs)
  • Mechanism of action of ARNIs
  • Indications and funding for sacubitril/valsartan
  • Pharmacological properties of sacubitril/valsartan
  • Efficacy & safety of sacubitril/valsartan
  • Patient selection for sacubitril/valsartan
  • Dosing & titration of sacubitril/valsartan

Contributing experts

Expert commentary is provided by Dr Raewyn Fisher, cardiologist at Waikato DHB, clinical director of the Waikato community-based Heart Failure Service and current Chair of the Heart Failure Working Group of the NZ Cardiac Society. 

Module questions have been developed by Dr Chris Tofield who works part time in General Practice in Tauranga, New Zealand, is involved in clinical research and is a clinical advisor to the Bay of Plenty District Health Board.

Accreditation

Accreditation number: 2020/03; Expiry 11/02/2022. This online learning activity has been accredited by PSNZ ENHANCE for 1 hour of group 2 learning and pharmacists may allocate 2 group 2 points on successful completion of this learning activity evidenced by receipt of Research Review Certificate of Completion.

References

  1. McMurray JJ, et al. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail. 2013 Sep;15(9):1062-73.
  2. Medsafe. New Zealand Data Sheet. Entresto 24/26® film-coated tablets; Entresto 49/51® film-coated tablets; Entresto 97/103® film-coated tablets. Available at: https://www.medsafe.govt.nz/profs/Datasheet/e/entrestotab.pdf [Accessed April 2019].
  3. Pharmac. Online Pharmaceutical Schedule. April 2019. Angiotensin II Antagonists with Neprilysin Inhibitors. Available at: https://www.pharmac.govt.nz/.
  4. Mosterd A & Hoes AW. Clinical epidemiology of heart failure. Heart. 2007 Sep;93(9):1137-1146.
  5. Bleumink GS, et al. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure: The Rotterdam Study. Eur Heart J. 2004 Sep;25(18):1614-1619.
  6. Redfield MM, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003 Jan 8;289(2):194-202.
  7. Van Riet EE, et al. Prevalence of unrecognized heart failure in older persons with shortness of breath on exertion. Eur J Heart Fail. 2014 Jul;16(7):772-777.
  8. Filippatos G, et al. Heart failure diagnosis and prognosis in the elderly: the proof of the pudding is in the eating. Eur J Heart Fail. 2011 May;13(5):467-471.
  9. Maggioni AP, et al. EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Study (ESC-HF Pilot). Eur J Heart Fail. 2013 Jul;15(7):808-817.
  10. McMurray JJ, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004.
  11. NHFA CSANZ Heart Failure Guidelines Working Group. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Guidelines for the Prevention, Detection, and Management of Heart Failure in Australia 2018. Heart Lung Circ. 2018 Oct;27(10):1123-1208.
  12. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med. 1991 Aug 1;325(5):293–302.
  13. Granger CB, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003 Sep 6;362(9386):772–776.
  14. Packer M, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS study group. Circulation. 1999 Dec 7;100(23):2312–2318.
  15. Konstam MA, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009 Nov 28;374(9704):1840–1848.
  16. Desai AS, et al. Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. Eur Heart J. 2015 Aug 7;36(30):1990-7.
  17. Packer M. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation. 2015 Jan 6;131(1):54-61.
  18. Jhund PS, et al. Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF. Eur Heart J. 2015 Oct 7;36(38):2576-84.
  19. Centers for Medicare & Medicacid Services. Readmissions Reduction Program (HRRP). Nov 2017. Available at: https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/AcuteInpatientPPS/Readmissions-Reduction-Program.html [Accessed April 2019].
  20. Desai AS, et al. Influence of sacubitril/valsartan (LCZ696) on 30-day readmission after heart failure hospitalization. JACC 2016 Jul 19;48(3):241-248.
  21. Lewis EF, et al. Preferences for quality of life or survival expressed by patients with heart failure. J Heart Lung Transplant. 2001 Sep;20(9):1016–1024.
  22. Lewis EF, et al. Health-related quality of life outcomes in PARADIGM-HF. Circ Heart Fail. 2017 Aug;10(8). pii: e003430. doi: 10.1161/CIRCHEARTFAILURE.116.003430.
  23. Chandra A, et al. Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. 2018 Jun 1;3(6):498-505.
  24. Vicent L, et al. Sacubitril/Valsartan in Daily Clinical Practice: Data From a Prospective Registry. J Cardiovasc Pharmacol. 2019 Feb;73(2):118-124.
  25. Martens P, et al. Impact of sacubitril/valsartan on heart failure admissions: insights from real-world patient prescriptions. Acta Cardiol. 2019 Apr;74(2):115-122.
  26. Lau CW, et al. Effects of sacubitril/valsartan on functional status and exercise capacity in real-world patients. Acta Cardiol. 2018 Nov 25:1-8. doi:10.1080/00015385.2018.1521 054. [Epub ahead of print].
  27. Antol DD, et al. An Early View of Real-World Patient Response to Sacubitril/Valsartan: A Retrospective Study of Patients with Heart Failure with Reduced Ejection Fraction. Adv Ther. 2018 Jun;35(6):785-795.
  28. Velazquez EJ, et al. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548.
  29. Gu J, et al. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010 Apr;50(4):401-14.
  30. Kobalava Z, et al. Pharmacodynamic and pharmacokinetic profiles of sacubitril/valsartan (LCZ696) in patients with heart failure and reduced ejection fraction. Cardiovasc Ther. 2016 Aug;349(4):191-198.
  31. Senni M, et al. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail. 2016 Sep:18(9):1193-1202.