A study on the mechanism of xanthine oxidase inhibitor withdrawal syndrome

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17168
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Okinaka Memorial Institute for Medical Research
• Principal Investigator: Kuwabara Masanari (財)冲中記念成人病研究所, その他部局等, 研究員 (20728290)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: キサンチンオキシダーゼ阻害薬 / 離脱症候群 / 尿酸 / 併用薬 / 死亡 / 心血管疾患

Outline of Final Research Achievements

In order to clarify the existence of xanthine oxidase inhibitor (XOI) withdrawal syndrome, we investigated the relationship between the onset of cardiovascular disease and death following discontinuation of XOI drugs. We purchased the receipt data from the JMDC (formerly the Japan Medical Data Center) and data from the Japanese Registry Of All cardiac and vascular Diseases (JROAD) in Japanese Circulation Society, and the analysis was approved by the Ethics Committee of Toranomon Hospital.
The results showed that the frequency of death was higher in the XOI discontinuation group, but most of the deaths occurred at the same time as other medications. On the other hand, few deaths were observed after discontinuation of XOI alone, and a direct causal relationship between XOI withdrawal and death could not be determined.
Additional detailed analysis about XOI withdrawal syndrome should be conducted in the future.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

本研究の結果として、これまでの報告と同様に、キサンチンオキシダーゼ阻害薬（XOI）の中止群で死亡の割合が高かったが、XOI中止した死亡患者のほとんどが他の薬も中止されていることが明らかとなり、XOI離脱と死亡との直接の因果関係については明らかにはできなかった。
本研究と通じて、薬の離脱においては、他の薬との関係についても調べることの重要性が明らかにされた。単剤を中止している患者を抽出することの難しさが本研究で明らかとなり、今後の研究を進める際には、他の薬との関係性も考慮に入れた解析が求められる。
今後も、他の交絡因子を踏まえたXOI離脱症候群の検討が必要と考えられる。