HYPERKALAEMIA CHALLENGE IN HF

Hyperkalaemia is a prevalent condition in your patients with heart failure1 and can jeopardise their beneficial RAASi therapy2

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RAASi therapy is vital

HK risk is exacerbated by RAASi

HK leads to suboptimal RAASi use

Current treatment options are limited

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Hyperkalaemia challenge in HF

RAASi therapy is vital

The goals of treatment in patients with HF are to improve their clinical status, functional capacity and quality of life, prevent hospital admission and reduce mortality.3 

  • Numerous landmark studies have shown that RAASi reduce mortality and morbidity and are associated with lower rates of hospitalisation in patients with HF.4-10
  • RAASi are the cornerstone of therapy in HF, and their use at the highest tolerated dose is recommended by multiple organisations.3,11

ACEis

HOPE (N=3,577)4
SOLVD (N=2,569)5

25%

Reduction in combined outcome of MI, stroke or CV mortality in patients at high CV risk4

26%

Risk reduction of HF-related hospital admissions or mortality in patients with congestive HF5

ARBs

CHARM (N=7,599)6

16%

Risk reduction in CV mortality or HF hospitalisation in patients with HF6

MRAs

RALES (N=1,663)7
EMPHASIS (N=2,737)8

30%

Reduction in risk of mortality in patients with HFrEF7

41%

Improvement in NYHA class7

35%

Lower frequency of hospitalisation for worsening HFrEF7

37%

Risk reduction in CV mortality or hospitalisation due to HFrEF8

ARNis

PARADIGM-HF (N=8,442)9
PARAGON-HF (N=4,822)10

21%

Reduction in risk of hospitalisation in patients with HFrEF9

20%

Reduction in risk of CV mortality in patients with HFrEF9

15%

Reduction in risk of HF hospitalisations in patients with HFpEF10
HR 0.85; 95% CI, 0.72–1.00

5%

Reduction in risk of CV mortality in patients with HFpEF10
HR 0.95; 95% CI, 0.79–1.16

HYPERKALAEMIA risk is exacerbated by RAASi

Guideline-directed use of RAASi has been cited as a major factor in the development of hyperkalaemia in patients with HF.12

  • In multiple clinical trials, RAASi use has been associated with an increased risk of hyperkalaemia, despite exclusion of high-risk groups.1,8,9,13

RAASi use has been associated with increased risk of hyperkalaemia in multiple clinical trials13

Bar chart: heart failure trials show RAASi linked to higher hyperkalaemia risk
Bar chart: heart failure trials show RAASi linked to higher hyperkalaemia risk

The impact of RAASi on the renin−angiotensin−aldosterone system12

Diagram: impact of RAASi on renal function
Diagram: impact of RAASi on renal function
Increased risk of
HK in clinical trials
Impact of RAASi on the renin–
angiotensin–aldosterone system

HYPERKALAEMIA leads to suboptimal RAASi use

Current guidelines recommend dose reduction or discontinuation of RAASi if persistent hyperkalaemia is a problem.3,14,15 As a result, hyperkalaemia is often a reason for withholding RAASi treatment.2

  • In a large Swedish study16 almost half of all patients discontinued MRA following an episode of hyperkalaemia within the first year of treatment, and in most patients therapy was not reintroduced during the following year. Discontinuation of concomitant ACEi/ARB use occurred in 23% of patients.

RAASi therapy is often withheld due to hyperkalaemia2

7,092
Outpatients

63.1
Mean age

82%
NYHA class II/III

Baseline 
comorbidities

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64.6%
With HTN

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34.3%
With DM

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17.8%
With CKD

Graphic: RAASi therapy is often withheld due to hyperkalaemia
Graphic: RAASi therapy is often withheld due to hyperkalaemia
Graphic: RAASi therapy is often withheld due to hyperkalaemia

Study information
QUALIFY was an international prospective longitudinal survey of outpatients with chronic HF recruited 1–15 months after hospitalisation for HF

However, reducing or stopping RAASi is associated with an increased risk of mortality and morbidity,17-19 and an increased likelihood of hospitalisation.18 

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Physicians, therefore, are faced with the dilemma of using RAASi and accepting hyperkalaemia or reducing/stopping RAASi and accepting poorer clinical outcomes

What is needed is a therapy that allows HF patients to stay on beneficial RAASi therapy with reliable and predictable long-term control of serum K+ levels.

Mortality risk doubles when RAASi is reduced or stopped17

Bar chart: mortality risk in HF doubles when RAASi is reduced or stopped

Current treatment options for chronic HYPERKALAEMIA are limited

Both short- and long-term treatment strategies are critical for the management of hyperkalaemia.20 However, currently available options focus mainly on emergency and intermediate care, and there are substantial limitations associated with current treatment options for chronic hyperkalaemia:20

Image: current treatment options for chronic hyperkalaemia are limited

Dietary modifications may lead to restricted consumption of healthy foods,21 and it may be very difficult for patients already on a restricted diet to adhere to further dietary modifications.22,23 The effects of dietary interventions on outcomes are uncertain22

Image: current treatment options for chronic hyperkalaemia are limited

Traditional K+-binders (SPS and CPS) can be associated with life-threatening GI side effects and hypokalaemia24,25 and may not be suitable in those who cannot tolerate an increase in sodium (SPS)25

Image: current treatment options for chronic hyperkalaemia are limited

Loop diuretics at the lowest achievable dose are recommended for the symptomatic management of congestion in patients with HFrEF26

Their use in patients to manage hyperkalaemia can result in worsening of renal function, contraction of plasma volume, and lower blood pressure26 

Their use may also hamper the up-titration of guideline-recommended doses of ACEi/ARB26

In a real-world observational study reduction in dose of loop diuretics was associated with better clinical outcomes vs no dose reduction, but 76% of patients remained on the same dose, contrary to guidelines27

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There is an unmet need for a reliable long-term option for the management of chronic hyperkalaemia that enables patients to continue RAASi therapy at target doses20

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Notice how reliable and easy to use Veltassa® can help
keep your HF patients on their vital RAASi therapy

References & footnotes

ACEi, angiotensin II converting enzyme inhibitor; ARB, angiotensin II-receptor blocker; ARNi, angiotensin-receptor neprilysin inhibitor; CHARM, Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity; CI, confidence interval; CONSENSUS, Cooperative North Scandinavian Enalapril Survival Study; CPS, calcium polystyrene sulfonate; CKD, chronic kidney disease; CV, cardiovascular; DM, diabetes mellitus; EMPHASIS, Eplerenone in Mild Patients Hospitalization and Survival Study; EPHESUS, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HK, hyperkalaemia; HOPE, Heart Outcomes Prevention Evaluation; HR, hazard ratio; HTN, hypertension; I-PRESERVE, Irbesartan in HF patients with a preserved ejection fraction; K+, potassium ions; MI, myocardial infarction; MRA, mineralocorticoid-receptor antagonist; NYHA, New York Heart Association; PARADIGM, Prospective Comparison of ARNi with ACEi to Determine Impact on Global Mortality and Morbidity; PARAGON, Prospective Comparison of ARNi with ARBi Global Outcomes in HF with Preserved Ejection Fraction; QUALIFY, The Quality of Adherence to Guideline Recommendations for Life-saving Treatment in Heart Failure; RAASi, renin−angiotensin−aldosterone system inhibitors; RALES, Randomized Aldactone Evaluation Study; SOLVD, Studies of Left Ventricular Dysfunction; SPS, sodium polystyrene sulfonate; TOPCAT, Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist.

References: 

1. Thomsen RW, et al. J Am Heart Assoc 2018;7(11):e008912. 2. Komajda M, et al. Eur J Heart Fail 2016;18(5):514−22. 3. Ponikowski P, et al. Eur J Heart Fail 2016;18(8):891−975. 4. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000;355(9200):253−9. 5. SOLVD Investigators. N Engl J Med 1991;325(5):293−302. 6. Desai AS, et al. J Am Coll Cardiol 2007;50(20):1959–66. 7. Pitt B, et al. N Engl J Med 1999;341(10):709−17. 8. Zannad F, et al. N Engl J Med 2011;364:11–21. 9. McMurray JJ, et al. N Engl J Med 2014;371(11):993−1004. 10. Solomon SD, et al. N Engl J Med 2019;381(17):1609−20. 11. Yancy CW, et al. Circulation 2017;136(6):e137−e161. 12. Palmer BF. N Engl J Med 2004;351(6):585−92. 13. Tromp T, van der Meer P. Eur Heart J 2019;21(Suppl A):A6−11. 14. Yancy CW, et al. J Am Coll Cardiol 2013;62(16):e147−e239. 15. Lindenfeld J, et al. J Card Fail 2010;16(6):e1−e194. 16. Trevisan M, et al. Eur J Heart Fail 2018;20(8):1217−26. 17. Epstein M, et al. Am J Manag Care 2015;21(11 Suppl):S212−S220. 18. Ouwerkerk W, et al. Eur Heart J 2017;38(24):1883−90. 19. Martens P, et al. Acta Cardiol 2020; doi: 10.1080/00015385.2020.1771885. 20. Dunn JD, et al. Am J Manag Care 2015;21(15 Suppl):S307−S315. 21. National Kidney Foundation. The DASH Diet. Available at: kidney.org/atoz/content/Dash_Diet (accessed July 2020). 22. Palmer SC, et al. Cochrane Database Syst Rev 2017;4:CD011998. 23. Vendramini LC, et al. Braz J Med Biol Res 2012;45(9):834−40. 24. Calcium Resonium PI. Sanofi 2018. 25. Kayexalate® US PI. Sanofi 2017. 26. Ter Maaten JM, et al. Clin Res Cardiol 2020;109(8):1048−59. 27. Kapelios CJ, et al. Eur J Heart Fail 2020; doi: 10.1002/ejhf.1796.