HYPERKALAEMIA IN HF PATIENTS

Hyperkalaemia can be life-threatening in patients with heart failure1

Although patients with hyperkalaemia are typically asymptomatic, the condition can become life-threatening if left untreated1

Small body figure image with heart highlighted
Small body figure image with heart highlighted
Yellow clipboard icon
Yellow clipboard icon

To increase the chance of early diagnosis and treatment, it’s important to be able to identify patients at high risk of developing hyperkalaemia.1

High-risk patients include individuals with:

  • Heart failure (HF) with recurrent hyperkalaemia2,3
  • HF and undergoing optimisation with RAASi therapy1,2,4

In addition, there are other patient groups at high risk of hyperkalaemia, including those with chronic kidney disease (CKD), resistant hypertension and diabetic nephropathy.1

Learn more about hyperkalaemia with expert cardiologist Dr Javed Butler

  1. Renal Association Clinical Practice Guidelines 2014. Treatment of Acute Hyperkalemia in Adults. 
  2. Nilsson E, et al. ERA-EDTA, Madrid, 2017. Poster presentation SP313. 
  3. Kovesdy, CP. Nat. Rev. Nephrol. 2014; 10: 653–662. 
  4. Vardeny O, et al. Circ Heart Fail. 2014; 7: 573-579.  

HYPERKALAEMIA IN HF PATIENTS

Mechanism of HF & RAASi therapy that could lead to hyperkalaemia

Renal function often declines with progressive HF, which results in reduced GFR and depleted potassium excretion.1,2

A number of medications, including commonly used HF treatments disrupt the RAAS, which results in decreased aldosterone production and depleted potassium excretion.1,2

Diagram to show how different pharmacological interventions can disrupt the renin–angiotensin–aldosterone system and its effects on the kidneys, resulting in hyperkalaemia
Diagram to show how different pharmacological interventions can disrupt the renin–angiotensin–aldosterone system and its effects on the kidneys, resulting in hyperkalaemia

Adapted Palmer BF. N Engl J Med. 2004;351:585-92.3

RAASi, renin-angiotensin-aldosterone system inhibitors

GFR, glomerular filtration rate

References:

  1. Desai AS et al. J Am Coll Cardiol. 2007;50:1959-66.
  2. National Kidney Foundation. 2014. Clinical update on hyperkalemia.
  3. Palmer BF. N Engl J Med. 2004;351:585-92.

HYPERKALAEMIA IN HF PATIENTS

Hyperkalaemia is common in heart failure patients, and often prevents patients achieving guideline recommended RAASi1-3

In an observational study in Sweden:1

24% of adult patients with CHF developed hyperkalaemia within 3 years
24% of adult patients with CHF developed hyperkalaemia within 3 years

of adult patients with HF developed hyperkalaemia within 3 years

13% of adult patients using RAASi developed hyperkalaemia within 3 years
13% of adult patients using RAASi developed hyperkalaemia within 3 years

of adult patients using RAASi developed hyperkalaemia within 3 years

ADJUSTED
OR 1.14

for hyperkalaemia
patients with HF*1

RAASi, renin-angiotensin-aldosterone system inhibitors

*Reference group: patients without HF

References:

  1. Nilsson E, et al. ERA-EDTA, Madrid, 2017. Poster presentation SP313.
  2. Epstein M et al. Am J Manag Care 2015; 21: S212-S220.
  3. Maggioni AP et al. Eur J Heart Fail. 2013; 15: 1173-84.

HYPERKALAEMIA IN HF PATIENTS

RAASi use is associated with a higher risk of hyperkalaemia*1,2

A high number of heart failure patients are on not on guideline recommended RAASi treatment3,4

In the ESC-HF Long-Term Registry, 2-12% of patients were not receiving the guideline-recommended target dose of pharmacological treatment due to past or current hyperkalaemia.4

Risk of hyperkalaemia with RAASi use1,2

An important risk factor for an incident hyperkalaemia event was concomitant use of RAASi.**2

UK study

ACEis
OR 13.63

ARBs
OR 15.89

MRAs
OR 7.7

Sweden study

ACEis
OR 1.5

ARBs
OR 1.21

MRAs
OR 1.66

RAASi, renin-angiotensin-aldosterone system inhibitors

MRA, mineralocorticoid-receptor antagonist

ACEi, angiotensin-converting-enzyme inhibitor

ARB, angiotensin receptor blocker

*Based on a multivariable logistic regression analysis in an observational study in Sweden. Reference group: a large group of heterogeneous healthcare users that did not use ACEis, ARBs or MRAs1

**Based on retrospective population-based risk factor analysis in the UK. Reference group: Patients with hyperkalaemia that did not use ACEis, ARBs or MRAs.2

References:

  1. Nilsson E, et al. ERA-EDTA, Madrid, 2017. Poster presentation SP313.
  2. Horne L, et al. ERA-EDTA, Madrid, 2017. Poster presentation MP370.
  3. Epstein M et al. Am J Manag Care 2015; 21: S212-S220.
  4. Maggioni AP et al. Eur J Heart Fail. 2013; 15: 1173-84.

HYPERKALAEMIA IN HF PATIENTS

RAASi, renin-angiotensin-aldosterone system inhibitors

*Compared to optimal RAASi treatment.

**Compared to normokalaemia (serum K+ ≤5.0 mEq/L ) in a retrospective US cohort (N=15,803) of cardiovascular disease patients treated with antihypertensives.

References:

  1. Epstein M et al. Am J Manag Care 2015; 21: S212-S220.
  2. Jain N, et al. Am J Cardiol 2012;109:1510–1513.
  3. Michel A et al. Eur J Heart Fail. 2015;17(2):205-13.

HYPERKALAEMIA IN HF PATIENTS

Burden of RAASi dose reduction or discontinuation

Patients on sub-maximum or discontinued RAASi are at 2x higher risk of death*1 

In a retrospective observational cohort study over 12 months, 20% patients on ACEis and 31% patients on ARBs had serum potassium levels >5.0 mEq/L.2

RAASi, renin-angiotensin-aldosterone system inhibitors

ACEi, angiotensin-converting-enzyme inhibitor

ARB, angiotensin receptor blocker

*Maximum RAASi was defined as the labelled dose

References:

  1. Epstein M et al. Am J Manag Care 2015; 21: S212-S220.
  2. Sadjadi SA et al. Ther Clin Risk Manag. 2009; 5(3): 547-552.

HYPERKALAEMIA IN HF PATIENTS

There is a need for additional treatment options for hyperkalaemia1

The goal of long-term control of serum potassium is to prevent recurrence of hyperkalaemia

 

Critical care management of hyperkalaemia

Many hyperkalaemia patients are treated in the acute setting, where the main goal is to restore normal membrane
potential and prevent cardiac arrhythmia.1

Protect the heart:2

  • Intravenous calcium salts

Shift potassium into cells:2

  • Sodium bicarbonate
  • Insulin/glucose
  • β2 agonists

Remove excess potassium from the body:2

  • Diuretics
  • Cation exchange resin (mild-moderate hyperkalaemia)
  • Dialysis

 

Long-term management of hyperkalaemia

Hyperkalaemia is episodic and may represent a chronic problem for patients with HF. Ongoing monitoring and long-term maintenance therapy may be necessary to avoid further risk of recurrent hyperkalaemia.3,4

Historically, there have been number of therapeutic options available, both pharmacological and non-pharmacological. Whilst they are associated with some benefits, treatment options are still limited.

PHARMALOGICAL THERAPIES

Caution exchange resins

  • Cases of intestinal injury have been reported in association with calcium polystyrene sulfonate (CPS) and sodium polystyrene sulfonate (SPS)5-8
  • Lack of clinical data to support use beyond 7 days of treatment9-12
  • Intestinal intolerance has been reported in association with CPS and SPS, including nausea, vomiting, gastric irritation, constipation and diarrhoea5-8

Patiromer

  • Indicated in the treatment of hyperkalaemia, but should not replace emergency treatment for life-threatening hyperkalaemia13

NON-PHARMALOGICAL THERPAIES

Low potassium diet

  • Doesn’t tackle the underlying cause of hyperkalaemia and has limited effectiveness and variable patient compliance14,15

OTHER OPTIONS

Renin-angiotensin-aldosterone system inhibition (RAASi) dose reduction

  • RAASi is beneficial for the preservation of cardio-renal function, and dose reduction is associated with an increased risk of mortality*16,17

*Compared to patients on maximum doses of RAASi

References:

  1. National Kidney Foundation, 2014. Clinical Update on Hyperkalaemia.
  2. Renal Association Clinical Practice Guidelines 2014. Treatment of Acute Hyperkalemia in Adults.
  3. Einhorn LM et al. Arch Intern Med. 2009; 169: 1156-62.
  4. Sarwar CMS et al. J Am Coll Cardiol. 2016; 68: 1575-89.
  5. Sanofi-Aventis. Calcium resonium® Summary of Product Characteristics.
  6. Sanofi-Aventis. Resonium A® Summary of Product Characteristics.
  7. Sanofi-Aventis. Calcium resonium® Prescribing information.
  8. Sanofi-Aventis. Kayexalate® Prescribing information.
  9. Lepage L et al. Clin J Am Soc Nephrol. 2015;10:2136-42.
  10. Nasir K & Ahmad A. J Ayub Coll Abbottabad. 2014; 26:455-8.
  11. Gruy-Kapral C et al. J Am Soc Nephrol. 1998;9:1924-30.
  12. Emmett M et al. Gastroenterol. 1995 Mar;108:752-60.
  13. Vifor Pharma. Veltessa (patiromer) summary of product characteristics.
  14. Packham DK & Kosiborod M. Am J Cardiovasc Drugs. 2016;16:19-31.
  15. Sanghavis S et al. Semin Dial. 2013;26:597-603.
  16. Epstein M et al. Am J Manag Care 2015; 21: S212-S220.
  17. Maggioni AP et al. Eur J Heart Fail. 2013;15:1173-84.

HYPERKALAEMIA IN HF PATIENTS

Summary

Hyperkalaemia is a metabolic condition characterised by elevated serum K+ levels (>5.0 mEq/L)1

Hyperkalaemia is common in heart failure patients, and often prevents patients achieving guideline recommended RAASi2-4

Hyperkalaemia and subsequent suboptimal RAASi treatment is associated with increased morbidity and mortality*3

There is a need for additional treatment approaches in hyperkalaemia5

RAASi, renin-angiotensin-aldosterone system inhibitors

*Compared to optimal RAASi therapy

References:

  1. Rastergar MS. Postgrad Med J. 2001;77: 759-764. 
  2. Nilsson E, et al. ERA-EDTA, Madrid, 2017. Poster presentation SP313
  3. Epstein M et al. Am J Manag Care 2015; 21: S212-S220.
  4. Maggioni AP et al. Eur J Heart Fail. 2013;15:1173-84.
  5. National Kidney Foundation. 2014. Clinical update on hyperkalemia.