Heart failure module 5: special cases in heart failure

Released1 November 2017     Expires: 01 November 2019      Programme:

Hyperkalaemia treatment

The goal of emergency treatment of hyperkalaemia is to treat/prevent the associated arrhythmic complications and is generally only required for patients with serum potassium greater than 6.0 mmol/L (figure 5).

Figure 5. Emergency management of hyperkalaemia
Figure 5. Emergency management of hyperkalaemia
Potassium binders

Until recently, there have been limited options for patients who develop drug-related hyperkalaemia; the usual compromise is either dose reduction or withdrawal of the medication altogether.50

Calcium resonium, a polymer derived from polystyrene which absorbs potassium ions in the gut, is useful in the acute setting to increase potassium excretion. However, the polymer swells when in contact with water and gastrointestinal (GI) complications are common making it unsuitable for longer term use.51

Newer potassium binders are non-absorbable compounds that bind potassium in the gut without such high rates of GI side effects. Two drugs have been investigated for the treatment and prevention of hyperkalaemia in patients with heart failure; patiromer and sodium zirconium cyclosilicate (ZS-9).52


Patiromer for the treatment of hyperkalaemia in patients with heart failure was studied in the PEARL-HF (Evaluation of RLY016 in Heart Failure Patients) trial (n =105, average age 68 years, average LVEF 40%, patients had previously had medication discontinued for hyperkalaemia or had CKD). All patients (except two in the placebo arm) were taking an ACE inhibitor or an ARB and all patients started spironolactone 25 mg on the same day as the study drug.53

Treatment with patiromer (30 g per day for four weeks) was associated with a lower rate of hyperkalaemia (≥5.5 mmol/L) compared to placebo (7% vs. 25%). This allowed the dose of spironolactone to be increased (from 25 mg to 50 mg, once daily) in a higher proportion of patients taking patiromer compared with placebo (91% vs. 74%, respectively).

Adverse event rate was low: 7% of patients required discontinuation of the study drug. GI disturbances such as flatulence, diarrhoea and constipation were the most commonly reported in the patiromer group.


Subgroup analysis of HARMONIZE (Hyperkalaemia Randomised Interventions Multi-dose ZS-9 Maintenance Study) found that ZS-9 is a safe and effective treatment for hyperkalaemia (> 5.1 mmol/L) in patients with heart failure (n=94, 70% had CKD or diabetes, 69% taking ACE inhibitors, ARBs or MRAs).54

ZS-9 reduced potassium levels to <5.0 mmol/L in 93% of patients during the initial ‘treatment’ phase of the study, during which all patients received the drug. ZS-9 was more effective for maintaining serum potassium levels <5.0 mmol/L compared to placebo in the subsequent ‘maintenance’ phase (83% vs. 40%, p<0.01).

There were no serious adverse events or events that led to study drug discontinuation during the treatment phase. The adverse event rate was similar between the ZS-9 and placebo groups during the maintenance phase. The most common adverse event in the ZS-9 group was peripheral oedema, the clinical significance of which is not clear with such small numbers.

Additionally, analysis of patients with potassium levels ≥6.0 mmol/L (n=45) from all studies of ZS-9 has found that 80% of patients achieved potassium levels <6.0 mmol/L within four hours of starting treatment:55 ZS-9 may also be helpful for the emergency management of severe hyperkalaemia but is not yet licenced for use in either the acute or chronic setting.

The problem of hypokalaemia
Although potassium levels ≤3.5 mmol/L was uncommon in PEARL-HF (6%), almost half of patients taking patiromer had potassium levels ≤4.0 mmol/L after four weeks of treatment.

It’s not at all clear whether MRAs mediate some or all of their effect by preventing hypokalaemia: patients with heart failure who take potassium-sparing diuretics have lower risk of adverse outcome compared to those taking non-potassium sparing diuretics.56 Furthermore, potassium levels 5.0–5.5 mmol/L are associated with the lowest risk of adverse outcome in patients with chronic heart failure.5 In a patient who has to stop or reduce MRA for hyperkalaemia, there is no evidence that taking both an MRA and a potassium binder is better than taking neither.


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