ENGAGE AF- TIMI 48 試験におけるエドキサバンによる結末に対する腎機能の影響
Erin A Bohula1, Robert P Giugliano2, Christian T Ruff2
1From the TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. ebohula@partners.org.
Circulation
|July 1, 2016
まとめ
エドキサバン (高用量療法) は,すべての腎臓機能レベルにおいて,脳卒中予防におけるワルファリンと同様の効果と出血の減少を示した. エドキサバンが優れている.
科学分野:
- 心臓病科
- 薬理学について
- 腎臓科
背景:
- エドキサバンは口服用ファクターXA阻害剤で,以前は心臓発作や全身栓塞 (S/ SE) の予防にワーファリンに劣らず,心房細動 (AF) の患者で出血の減少が顕著であった.
- この研究は,ENGAGE AF- TIMI 48試験のベースラインクレアチニンクリアランス (CrCl) の異なる度合いにおける高用量エドキサバン療法の有効性と安全性に焦点を当てています.
研究 の 目的:
- エドキサバンとワルファリンの有効性と安全性を評価する.
- 高用量エドキサバン療法 (HDER) の腎機能に関する効果を特に分析し,脳卒中/全身栓塞 (S/ SE) の予防と出血リスクに焦点を当てた.
主な方法:
- 中等から高度の脳卒中リスクのある14, 071人のAF患者は,ウォルファリンまたはHDER (特定のCrCl,体重,または併用薬の基準に応じて,投与量を30mgに減らす) にランダムに割り当てられました.
- CrCl < 30 mL/ min の患者は除外された. 効果 (S/ SE),安全性 (重度の出血),および臨床結果は,治療意図分析を用いて評価された.
- 分析は,事前に指定されたCrCl切断点 (50 mL/min) と,腎機能推定のためのCKD-EPI式を用いた感度分析を用いた.
主要な成果:
- ウォルファリンとHDERによるS/ SEの相対的なリスクは,CrCl>50mL/ minとCrCl>50mL/ minで類似していた (相互作用のP=0. 94).
- 探索的分析では,より高いCrClレベルでのHDERでS/ SEの予防に対する相対的な有効性が低いことが示された (CrCl>95mL/ min:HR1. 36,95%CI 0. 88- 2. 10;相互作用のP=0. 08).
- すべてのCrCl値において,HDERで出血率は一貫して低かった (相互作用のP=0. 11),腎機能に関係なくHDERでより好ましい臨床結果をもたらした (相互作用のP=0. 73).
結論:
- 血栓塞栓症を予防する相対的な有効性の潜在的低下は,CrClの上の範囲でHDERで観察されましたが,その安全性プロファイルは一貫しています.
- ウォルファリンと比較して,HDERの臨床上の純利益は腎機能の全スペクトルにわたって維持され,主に有利な出血プロフィールによる.
- これらの発見は,異なるレベルの腎機能を有するAF患者のHDERの使用を支持し,有効性と安全性のバランスを取る重要性を強調しています.
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