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Can Fam Physician. 2017 September; 63(9): 697.
PMCID: PMC5597015

Sacubitril-valsartan: novel therapy for heart failure

Evan Sehn
Doctor of Pharmacy student at the University of Alberta in Edmonton.
Terrence McDonald, MD MSc CCFP(SEM) DipSportMed
Assistant Clinical Professor and Researcher in the Department of Family Medicine at the University of Calgary in Alberta.

Clinical question

Is sacubitril-valsartan effective for systolic heart failure (HF)?

Bottom line

If 36 patients with HF are switched from angiotensin-converting enzyme inhibitors (ACEIs) to sacubitril-valsartan, 1 fewer dies and 1 fewer is admitted for HF over 27 months. Aldosterone antagonists and β-blockers should be given first and continued concurrently.

Evidence

  • In 1 RCT,1 8399 patients with systolic HF (mean age 64, about 94% class II or III, B-type natriuretic peptide [BNP] level about 250 ng/L, about 7% North American) switched from ACEIs to sacubitril-valsartan (200 mg) twice daily or enalapril (10 mg) twice daily.
    • -At 27 months, sacubitril-valsartan statistically significantly reduced cardiovascular death or HF hospitalization (22% vs 27%, number needed to treat [NNT] = 22); cardiovascular death (13% vs 17%, NNT = 32); HF hospitalization (13% vs 16%, NNT = 36); all-cause mortality (17% vs 20%, NNT = 36); and mean blood pressure by about 3 mm Hg. There were fewer discontinuations for renal impairment (0.7% vs 1.4%, NNT = 143).
    • -Adverse effects were fewer (10.7% vs 12.3%, NNT = 63), but symptomatic hypotension (14% vs 9.2%, number needed to harm = 20) and angioedema (19 vs 10 patients) increased.
    • -Limitations of the trial: about 20% withdrew during runin, it stopped early, and it was industry sponsored.

Context

  • The usefulness of initiating therapy based on BNP levels is unknown, as most HF patients have elevated levels.2
  • About 93% of participants were taking β-blockers and half were taking aldosterone antagonists concurrently.1
  • Aldosterone antagonists, ACEIs, and β-blockers each reduce relative risk all-cause mortality by 20% to 30%.3
  • Guidelines recommend replacing ACEIs or angiotensin receptor blockers with sacubitril-valsartan if patients take ACEIs, β-blockers, and aldosterone antagonists with elevated natriuretic peptide levels or were hospitalized for HF in the past 12 months.4,5
  • Initial dose is 50 to 100 mg twice daily with possible titration to 200 mg in 2 to 4 weeks.6 About 40% need a reduction (but one-third are able to return to the full dose).7
  • Although not covered by many insurance plans, it is a recommended benefit.8 Cost is about $250 per month.

Implementation

To switch between sacubitril-valsartan and ACEIs, a 36-hour washout is recommended to prevent angioedema.6 The valsartan in the 50-, 100-, and 200-mg combinations is equivalent to common valsartan doses of 40, 80, and 160 mg.6 Sacubitril-valsartan might have stronger diuretic and natriuretic effects than valsartan alone,9 and blood pressure, fluid status, and diuretic dose should be monitored. Sacubitril-valsartan raises BNP levels. If natriuretic peptide measurement is needed, N-terminal pro-BNP level is preferred, as it is not affected by sacubitril-valsartan.6

Notes

Tools for Practice articles in Canadian Family Physician (CFP) are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in CFP are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to ac.cpfc@ecitcarprofsloot. Archived articles are available on the ACFP website: www.acfp.ca.

Footnotes

This article is eligible for Mainpro+ certified Self-Learning credits. To earn credits, go to www.cfp.ca and click on the Mainpro+ link.

Cet article se trouve aussi en français à la page 698.

Competing interests

None declared

The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

References

1. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004. [PubMed]
2. Latour-Pérez J, Coves-Orts FJ, Abad-Terrado C, Abraira V, Zamora J. Accuracy of B-type natriuretic peptide levels in the diagnosis of left ventricular dysfunction and heart failure: a systematic review. Eur J Heart Fail. 2006;8(4):390–9. [PubMed]
3. Lindblad AJ, Allan GM. Aldosterone antagonists in systolic heart failure. Can Fam Physician. 2014;60:e104. Available from: www.cfp.ca/content/cfp/60/2/e104.full.pdf. Accessed 2017 Jul 28. [PMC free article] [PubMed]
4. Moe GW, Ezekowitz JA, O’Meara E, Lepage S, Howlett JG, Fremes S, et al. The 2014 Canadian Cardiovascular Society heart failure management guidelines focus update: anemia, biomarkers, and recent therapeutic trial implications. Can J Cardiol. 2015;31(1):3–16. Erratum in: Can J Cardiol 2016;32(3):394. [PubMed]
5. Howlett JG, Chan M, Ezekowitz JA, Harkness K, Heckman GA, Kouz S, et al. The Canadian Cardiovascular Society heart failure companion: bridging guidelines to your practice. Can J Cardiol. 2016;32(3):296–310. [PubMed]
6. Entresto [product monograph]. Dorval, QC: Novartis Pharmaceuticals Canada Inc; 2016.
7. Vardeny O, Claggett B, Packer M, Zile MR, Rouleau J, Swedberg K, et al. Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial. Eur J Heart Fail. 2016;18(10):1228–34. [PMC free article] [PubMed]
8. Canadian Agency for Drugs and Technologies in Health. CADTH Canadian Drug Expert Committee final recommendation: sacubitril/valsartan. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health; 2016.
9. Wang TD, Tan RS, Lee HY, Ihm SH, Rhee MY, Tomlinson B, et al. Effects of sacubitril/valsartan (LCZ696) on natriuresis, diuresis, blood pressures, and NT-proBNP in salt-sensitive hypertension. Hypertension. 2017;69(1):32–41. [PubMed]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada