非ステロイド抗炎症薬の心血管安全性の評価
1From Cardiovascular Division, Brigham and Women's Hospital, Boston, MA; and Clinical and Translational Science Center, Harvard Medical School, Boston, MA. eantman@rics.bwh.harvard.edu.
Circulation
|May 24, 2017
まとめ
薬剤の心血管安全性を評価するランドマイズされた第4相試験 (RCT) が実施された. 非ステロイド性抗炎症薬 (NSAID) の関節炎に対する試験は困難で,低用量セレコキシブは同様の心血管リスクを示しているが,痛み緩和は少ない.
科学分野:
- 薬理学について
- 心血管医学
- 臨床試験の設計
背景:
- 非心臓血管薬は心臓血管の健康に悪影響を及ぼします.
- 米国食品医薬品局は,重要な心血管安全上の懸念を考慮して,市場公開後の4段階のランダム化比較試験 (RCT) を義務付けています.
- 現在進行中の第4段階RCTでは,安全性が有効性より優先され,非劣等性設計を用いる.
研究 の 目的:
- 市場投入後の第4段階RCTにおける心血管安全性評価に影響を与える要因を調査する.
- 関節炎における非ステロイド性抗炎症薬 (NSAID) の心臓血管安全性試験の実施と解釈における課題を評価する.
- セルコキシブの心血管リスクと有効性を他のNSAIDと比較する.
主な方法:
- 心血管安全に関する第4段階RCTにおける計画段階の選択の分析
- プロトコル遵守と中断率を含む,心血管安全信号の解釈に影響を与える要因の評価.
- 関節炎に使用されるNSAIDに関する既存の第4相RCTのレビュー.
主要な成果:
- プロトコルの遵守と試験の継続は,心血管安全信号のバイアスと解釈に大きな影響を与えます.
- 関節炎におけるNSAIDの試験では,鎮痛効果と患者のアデランスとリテランスの維持を比較する上で困難に直面しています.
- 低リスクの被験者における低用量のセレコキシブは,NSAIDと比較して心臓血管リスクが低かったが,鎮痛効果は低下した.
結論:
- 第4段階RCTにおける方法論的選択は,心血管安全性評価に重大な影響を及ぼします.
- NSAIDの心血管安全性試験の実施と解釈は,有効性,適合性,保持性を慎重に検討する必要があります.
- NSAID,特にセレコキシブを選択する際には,心血管安全性と鎮痛効果のバランスが重要です.
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