![]() Upon withdrawal of the drug, potassium levels increased again. This revealed a significant dose-dependent decrease in potassium levels within hours. Several large trials have been performed with ZS-9, the most important being a multicentre phase 3 trial (12) that included all kinds of patients with hyperkalaemia (n=753) receiving different doses of ZS-9 or placebo. ZS-9 is the other new potassium binder, which is more selective. *“The novel potassium binders patiromer and ZS-9 are highly effective in lowering serum potassium levels”* Adverse events were also slightly more common in patiromer-treated patients, however there was no difference in the frequency of serious side effects or events leading to discontinuation. ![]() But most importantly, 91% of the patiromer-treated patients could tolerate 50 mg/day spironolactone instead of 74% of the placebo-treated patients, which was a significant difference. However, 6% of the patients treated with patiromer were hypokalaemic (3.5 mmol/L), versus none in the placebo group. This translated into an efficacy (number of patients with hyperkalaemia) that was significantly higher in de patiromer versus the placebo group. After 2 weeks, spironolactone dose was uptitrated to 50 mg/day, and resulted a slight potassium level increase in both groups. This showed that potassium levels clearly decreased when patients were treated with patiromer, in contrast to potassium levels of placebo-treated patients, which increased upon spironolactone treatment. However, it was difficult to determine whether these adverse events were truly related to treatment, as this trial did not include a placebo group for comparison.Īnother study with patiromer is the PEARL-HF trial, which investigated the efficacy and safety of patiromer in 104 spironolactone-treated (25 mg/day) HF patients with high risk for hyperkalaemia (history of hyperkalaemia or eGFR <60 mL/min), in order to evaluate whether the dose of spironolactone could be enhanced when patiromer was used (11). Adverse events were modest and included worsening of CKD, hypomagnesaemia, worsening of hypertension, constipation, diarrhoea and hypoglycaemia. For both conditions a significant decrease in potassium levels was seen, which remained stable and increased again upon withdrawal of the treatment. The efficacy and safety of low- and high dose patiromer treatment were evaluated. One of few trials evaluating patiromer is the AMETHYST-DN trial, which included 306 diabetic patients that had low eGFR (15-60 mL/min), who were on RAAS inhibition (RAASi) and had potassium levels >5mmol/L (10). ![]() By binding to potassium, potassium levels in the circulation are lowered. Patiromer and ZS-9 (sodium zirconium cyclosilicate) are two novel potassium binders that are currently under investigation. Therefore, there is a need for new treatment options for hyperkalaemia that are effective, safe and well-tolerated. These medications have, however, severe side effects, for instance affecting the gastrointestinal tract. These drugs exchange potassium for calcium. For chronic treatment, kayexalate and resonium calcium are indicated. ![]() This is, however, invasive and expensive and therefore not a preferable option. In case of very high potassium levels, dialysis can be done. Insulin, beta-adrenergic agonists and sodium bicarbonate are used in acute situations. Several therapeutic options exist for hyperkalaemia.
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