• Cardiology Clinical Trials
• Heart Failure

An investigational potassium binder, RLY5016, prevented hyperkalemia in patients with heart failure (HF), according to findings from the phase II PEARL-HF study (NCT00868439). The new agent may allow more HF patients to use renin-aldosterone-angiotensin system (RAAS) blockers, which have been shown to reduce mortality but cause hyperkalemia in up to 25% of HF patients.

The PEARL-HF study included 104 patients with HF and either stage 3 or 4 chronic kidney disease or a history of hyperkalemia that resulted in RAAS inhibitor discontinuation. Patients were randomly assigned to treatment with RLY5016 30 mg/day (n=55) or placebo (n=49). The primary endpoint was the change from baseline in serum potassium by Week 4. Bertram Pitt, MD, University of Michigan School of Medicine, Ann Arbor, Michigan, USA, presented findings from the PEARL-HF study.

At baseline, all patients were receiving standard heart failure therapy with a RAAS inhibitor or β-blocker. Patients also received spironolactone 25 mg/day for the first 2 weeks of the study, and those with serum potassium levels ≤5.1 mEq/L on Day 15 increased the spironolactone dose to 50 mg/day. More RLY5016-treated patients than patients in the placebo group were able to increase the spironolactone dose for the remaining 2 weeks of treatment (91% vs 74%; p=0.019).

After 4 weeks, treatment with RLY5016 reduced mean serum potassium levels from 4.69 mEq/L at baseline to 4.48 mEq/L (mean change, −0.22 mEq/L). By comparison, potassium levels increased in the placebo group from 4.65 mEq/L to 4.93 mEq/L (mean change, +0.23 mEq/L), resulting in a between-group difference of 0.45 mEq/L that favored RLY5016 (p<0.001).

The new potassium binder also provided protection against hyperkalemia, which was defined as serum potassium ≥5.5 mEq/L. Fewer patients in the RLY5016 group than in the placebo group developed hyperkalemia at any point during the study (7% vs 25%; p<0.05), regardless of the severity of renal dysfunction.

Currently available potassium binders are poorly tolerated, with a high risk of severe gastrointestinal side effects. In the PEARL-HF study, RLY5016 was well tolerated, with a withdrawal rate that was comparable to that seen in the placebo group (7% vs 6%). More patients reported at least 1 adverse event in the RLY5016 group than in the placebo group (54% vs 31%; p=0.019), but they were mostly mild gastrointestinal side effects.

Three patients in the RLY5016 group developed hypokalemia, which may be prevented by lower doses of the phosphate binder, Prof. Pitt said. Future studies will evaluate whether lower doses of RLY5016 can prevent hyperkalemia among patients who are taking life-saving RAAS inhibitors for the treatment of HF, she concluded.

• © 2010 MD Conference Express