新たなカリウム結合薬は心不全患者における高カリウム血症を軽減させる

PEARL-HF：新たな経口カリウム結合薬は心不全患者および慢性腎臓病を有する心不全患者における高カリウム血症を軽減させる

PEARL-HF: New oral potassium-binding agent reduces hyperkalemia in patients with heart failure and heart failure with chronic kidney disease

Phase 2b臨床試験の結果から、心不全患者および慢性腎臓病を有する心不全患者における高カリウム血症を管理する新たな治療法が得られる可能性がある、と2010年European Society of Cardiology学会のホットラインセッションで発表された。PEARL-HF（Parallel Evaluation of RLY5016 in Heart Failure：心不全におけるRLY5016のパラレル評価）スタディにより、新たに開発されたカリウム結合薬RLY5016が、アルドステロン拮抗薬を投与されている場合であっても、心不全患者や慢性腎臓病を有する心不全患者において高カリウム血症を調整するのに役立つことが示された。この多施設無作為化二重盲検プラセボコントロールトライアルは、104人の患者に治療用量のRLY5016（55人）またはプラセボ（49人）を投与し評価した。血清カリウムが4.3～5.1mEq/Lで慢性腎臓病を有し現在心不全治療薬を1種類以上内服している患者、または高カリウム血症により心不全治療を中断したことのある患者は、25～50mg/dayのアルドステロン拮抗薬スピロノラクトンも投与された。その結果、RLY5016はプラセボと比較し高カリウム血症の発現を有意に減少させた（7%対25%、P=0.015）。スピロノラクトンの用量を増加させることのできた患者の割合も多かった（91%対74%）。RLY5016の忍容性は良好で薬剤誘発性の重篤な有害事象は認められなかった。

Results from a recent phase 2b clinical trial presented during a Hotline session at ESC Congress 2010 may provide a new approach to managing excess potassium levels in patients with heart failure and heart failure with chronic kidney disease. The PEARL-HF study has shown that a newly developed potassium binder - known as RLY5016 - can help regulate hyperkalemia in such patients, even those receiving aldosterone antagonists.

Hyperkalemia is characterized by elevated serum potassium, which increases a patient's risk of cardiac arrhythmia and sudden death. At particular risk are heart failure patients, especially those with an underlying chronic kidney disease being treated with aldosterone antagonists. Although these drugs have shown life-saving benefits in multiple large outcome studies, their use is limited by the occurrence or fear of hyperkalemia.

Professor Bertram Pitt from the Division of Cardiovascular Medicine, University of Michigan School of Medicine, USA, who was steering committee chairman of the PEARL-HF (Parallel Evaluation of RLY5016 in Heart Failure), said: "The PEARL-HF trial demonstrates that RLY5016 effectively and safely lowers serum potassium and prevents hyperkalemia in patients with heart failure or heart failure with underlying renal impairment, even those using renin-angiotensin-aldosterone system antagonists. Currently, the risk of hyperkalemia has limited the use of these RAAS inhibitors, which exposes patients to further cardiac risk. These trial data are therefore very significant."

PEARL-HF was a multicentre, randomized, double blind, placebo-controlled trial, designed to evaluate the efficacy, safety and tolerability of RLY5016 in the prevention of hyperkalemia in heart failure patients. The study tested a total of 104 patients over four weeks; 55 with a therapeutic dose of RLY5016 and 49 with placebo. Patients with a serum potassium level of 4.3-5.1 mEq/L and chronic kidney disease currently taking one or more heart-failure therapies, or patients with a documented history of hyperkalemia that led to the discontinuation of a heart failure therapy, were also given a daily 25-50 mg dose of the aldosterone antagonist spironolactone.

The primary endpoint was the measured change from baseline in serum potassium. Efficacy was also evaluated by the proportion of patients with hyperkalemia and the proportion of patients whose spironolactone dose could be increased.

Results showed that RLY5016 significantly reduced the incidence of hyperkalemia compared to the placebo (7% vs. 25%, p=0.015). It also increased the proportion of patients whose spironolactone dose could be increased (91 percent vs. 74 percent, p=0.019). RLY5016 seemed well tolerated by patients, with a withdrawal rate from the study due to an adverse event of 7% (compared to 6% with the placebo), and there were no drug-related serious adverse events.