The future of HF management: How does potassium binding fit within pharmacological treatment of heart failure


News - May 22, 2016

Dickstein started off outlining the concept that HF is not a disease but a syndrome with multiple causes and converges many symptoms, making it a very large and heterogeneous population. This population is rapidly growing and prevalence estimates depend on how HF is defined. The costs of treating HF are enormous and are largely due to hospitalisation (60-65% of all costs).

Next to direct HF treatment, a substantial part of HF management is represented by treatment of concomitant therapeutic effects. In HF, guidelines recommend to use medications such as ACEi, ARBs and MRAs, which block the neurohormonal angiotensin system. Overactivity of this system dominates and worsens patient’s symptoms. Activity of this system is not only affected by the body itself but can also be affected by treatment, such as increased aldosterone plasma levels upon diuretic therapy.

*“A substantial part of HF management is represented by treatment of concomitant therapeutic effects”*

To improve management, several trials have been done to block the angiotensin system more strongly, such as VALIANT in 2003, CHARM-added in 2003, ValHeFT in 2002 and RESOLVD in 1999, including for example combination therapy of ACEi and ARBs. Nevertheless, these demonstrated only non-inferiority or slight benefit and included an increased frequency of adverse events such as worsening renal function and hyperkalaemia (13). Also the renin inhibitor aliskiren and the ACEi enalapril were tested as monotherapy as well as in combination, in patients with HF (ATMOSPHERE and PARADIGM trials) (14). This showed no difference in terms of long-term clinical outcome between monotherapy and combination therapy, however a significantly higher frequency of hyperkalaemia development was observed when treated with combination therapy, compared to monotherapy. This was even more apparent when MRAs were used at baseline.

A new agent in clinical trial that may improve HF management is LCZ696 (sacubitril/valsartan or ARNI therapy) (15). However, a study suggested that prior therapy optimisation resulted in a high frequency of patients with a contraindication for ARNI therapy as a result of side effects, such as hyperkalaemia.

Overall, the barriers of HF treatment with RAAS inhibition are similar to those that have been observed over the last 20 years, including creatinine increase, hypotension and risk for hyperkalaemia, as was demonstrated by the RALES, EPHESUS and EMPHASIS trials (16-18).

Nevertheless, insights have emerged on how to manage hyperkalaemia in HF. One study found eGFR<45 mL/min/1.73 m2, baseline [K+]>4.5 mEq/L on diuretics and BMI<26 kg/m2 as predictors of hyperkalaemia (K+>5.5 mE1/L) (19) and risk factors for hyperkalaemia with use of RAAS inhibitors include chronic kidney disease, decompensated HF, diabetes, volume depletion with decreased GFR and advanced age (20). Standard care in case of hyperkalaemia includes a low potassium diet, assessing renal function, reviewing medication history, titrating or discontinuing RAASi, applying diuretic therapy and/or potassium binder therapy.

Hyperkalaemia in at-risk patients is associated with increased mortality and frequent visits to the emergency department when potassium levels increase. Fear of hyperkalaemia can therefore be in the way of prescribing or optimally dosing RAAS inhibitor therapy. Indeed, uptake of guideline-recommended therapy for eligible patients is poor. If hyperkalaemia can be prevented with new agents such as patiromer and ZS-9, this will allow better treatment of a larger number of HF patients.


1. Courtesy, ESC Eurobservational 2015

2. Maggioni AP, et al., Eur J Heart Fail. 2013;15:1173-1184

3. Gheorghiade M, et al., Congest heart fail. 2012;18:9-17

4. Shirazian S, et al., Am J Med Sci. 2015 Jun;349(6):510-5

5. Epstein M, et al., Am J manag care 2015;21:S212-S220

6. Di Tano G, et al., Eur J Heart Fail. 2015;17:1032-1041

7. Vardeny O, et al., Circ Heart Fail 2014;7:573-579

8. Rossignol P, et al., Circ Heart Fail. 2014;7:51-58

9. Raebel MA, et al., Pharmacoepidemiology and drug safety 2007;16:55-64

10. Bakris GL, et al., JAMA. 2015 Jul 14;314:151-61.

11. Pitt B, et al., Eur Heart J 2011;32:820-828.

12. Packham DK, et al., N Engl J Med. 2015 Jan 15;372(3):222-31.

13. Phillips CO, et al., Arch intern med. 2007;167:1930-1936

14. Krum H, et al., Eur J Heart Fail. 2015;17:1075-1083

15. McMurray JJV, et al., N Engl J med. 2014;371:993-1004

16. Pitt B, et al., N Engl J Med 1999;341:709-717

17. Pitt B, et al., N Engl J Med 2003;348:1309-1321

18. Zannad F, et al., N Engl J Med 2011;364:11-21

19. Lazich I, et al., Semin Nephrol. 2014;34:333-339

20. Palmer BV. N Engl J Med 2004;351:585-592

Facebook Comments


We’re glad to see you’re enjoying PACE-CME…
but how about a more personalized experience?

Register for free