Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases

• Project/Area Number: 18K14954
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Nagoya City University
• Principal Investigator: HAGIWARA HIROMI 名古屋市立大学, 医薬学総合研究院(医学), 助教 (70793727)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 抗血小板薬 / 大規模医療情報 / リアルワールドデータ / 国際共同治験 / 民族差 / プラスグレル / クロピドグレル / 治験 / 大規模医療情報データベース

Outline of Final Research Achievements

Prasugrel inhibits platelet aggregation more potently and exerts therapeutic action faster than clopidogrel. In the global phase III trial conducted in Western and South American countries that excluded Asian countries, prasugrel reduced ischemic events but increased hemorrhagic risk compared with clopidogrel in patients with acute coronary syndrome scheduled for percutaneous coronary intervention. In the Japanese phase III trial for similar patients, the efficacy of prasugrel compared with clopidogrel was comparable to the global trial, but the safety could not be confirmed because of an insufficient number of patients.
Furthermore, given the strict enrollment criteria, the results of these trials may not be applicable to routine clinical practice. Accordingly, we compared the hemorrhagic risk of prasugrel and clopidogrel in real-world settings.The hemorrhagic risk was found to be greater with prasugrel than clopidogrel.

Academic Significance and Societal Importance of the Research Achievements

昨今の国際共同治験の促進により、日本人症例の組み入れが少ないまま有効性や安全性が検証され、承認される医薬品が多くなってきている。そこで、本研究では、治験時に日本人症例が少なく、日本人における有効性や安全性が明らかにされていないことに関し、日本人データを多数含む大規模医療情報データベースを活用した市販後の調査をすることを目的とした。本研究により、大規模データを用いた調査が、臨床試験時の民族差の課題を解決する一助となることを示した。出血リスクがより低く、かつ抗血小板効果が高く使用できる薬剤選択について検討し、日本人における抗血小板薬の適正使用につなげることができた。

Research Products

• [Journal Article] A comparison of the safety and effectiveness of prasugrel and clopidogrel in younger population undergoing percutaneous coronary intervention: A retrospective study using a Japanese claims database (2021)
  • Author(s): Hagiwara H, Fukuta H, Hashimoto H, Niimura T, Zamami Y, Ishizawa K, Kamiya T, Ohte N.
  • Journal Title: Journal of Cardiology Volume: 77 Issue: 3 Pages: 285-291
  • DOI: 10.1016/j.jjcc.2020.10.001
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases (2020)
  • Author(s): Hagiwara Hiromi、Fukuta Hidekatsu、Niimura Takahiro、Zamami Yoshito、Ishizawa Keisuke、Kimura Kazunori、Kamiya Takeshi、Ohte Nobuyuki
  • Journal Title: International Journal of Medical Sciences Volume: 17 Issue: 6 Pages: 728-733
  • DOI: 10.7150/ijms.43168
  • NAID: 120006956856
  • Peer Reviewed / Open Access
• [Presentation] Comparison of breeding risk between prasugrel and clopidogrel using the spontaneous reporting system of adverse drug events (2018)
  • Author(s): Hiromi Hagiwara, Hidekatsu Fukuta, Tatsuya Muto, Masahiro Tohkin, Takeshi Kamiya
  • Organizer: Ｔhe 18th World Congress of Basic and Clinical Pharmacology (WCP2018)
  • Int'l Joint Research
• [Presentation] 抗血小板薬クロピドグレルとプロトンポンプ阻害薬併用時における消化管出血リスクについて (2018)
  • Author(s): 萩原宏美、福田英克、神谷武
  • Organizer: 第3回日本臨床薬理学会 東海・北陸地方会