高齡患者服用新型抗凝藥重大出血研究

Major bleeding in the oldest patients taking novel oral anticoagulants

目的探討≧80歲高齡患者服用新型抗凝血藥(novel oral anticoagulants,NOACs)併用潛在相互作用藥物與重大出血發生的相關性。方法本研究為回顧性隊列研究,用本院醫療資訊系統採集2016年7月1日~2021年5月31日中服用NOACs(含Apixaban、Dabigatran、Edoxaban及Rivaroxaban)≧80歲患者資訊,包括人口統計學、共病、生理因素及藥物。結局終點設定為重大出血發生,以人-時間為概念計算結局發生率(incident rate,IR)、校正後發生率(adjusted incident rate,adjusted IR)、校正後發生率差(adjusted incident rate difference,adjusted IRD)及校正後發生率比值(adjusted rate ratio,adjusted RR)。本研究共納入12種有潛在相互作用的藥物,用泊松回歸模型分析每種藥物與NOACs併用的出血相關性,P<0.05有顯著性差異。結果在12種有潛在相互作用藥物中,與單獨應用NOACs相比,併用Amiodarone每人年重大出血的adjusted RR為3.82(95%CI,1.94-7.40),Aspirin為2.03(95%CI,1.02-3.84),Clopidogrel為2.27(95%CI,1.13-4.39),選擇性5-羥色胺再攝取抑制劑為3.12(95%CI,1.01-9.07),血栓通為3.92(95%CI,1.12-12.89);而Ginkgo組的adjusted RR為0.24(95%CI,0.05-0.74)。以上對比組P值均小於0.05,其餘藥物組無顯著性差異。結論≧80歲高齡患者服用NOACs時,當與Amiodarone、Aspirin、Clopidegrel、SSRIs或血栓通合用會增加重大出血的發生,臨床上須關注相互作用誘發的不良反應。

Objective To investigate whether there is a correlation between the occurrence of major bleeding and the use of potentially interacting drugs in the oldest patients(≥80 years old)taking novel oral anticoagulants(NOACs).Methods This was a retrospective cohort study.The hospital information system of Kiang Wu Hospital was used to collect information on patients aged 80 and above who received NOACs(including apixaban,dabigatran,edoxaban and rivaroxaban)from July 1,2016,to May 31,2021,which included basic demographics,comorbid factors,physiological factors,and medication records.The primary endpoint was the incidence of major bleeding.The incidence rate(IR),adjusted incidence rate(adjusted IR),adjusted incidence rate difference(adjusted IRD)and adjusted rate ratio(adjusted RR)were calculated based on the concept of persontime.A total of 12 interacting drugs were studied.The major bleeding correlation of each drug when combined with NOACs was analyzed by a Poisson regression model.There was a significant difference when the P value was less than 0.05.Results Among 12 drugs with potential interactions with NOACs,when compared with NOACs alone,the adjusted RR for major bleeding per person-year was 3.82(95%CI,1.94-7.40)for amiodarone and 2.03(95%CI,1.02-3.84)for aspirin.Clopidogrel and SSRIs were approximately 2.27(95%CI,1.13-4.39)and 3.12(95%CI,1.01-9.07),respectively.In addition,3.92(95%CI,1.12-12.89)was found for the Xue Shuan Tong group.The adjusted RR of the Ginkgo group was 0.24(95%CI,0.05-0.74).The P values of the above comparison groups were all less than 0.05.Other groups had no significant difference.Conclusion In the oldest patients taking NOACs,there was an increased incidence of major bleeding when combined with amiodarone,aspirin,clopidogrel,SSRIs,or Xue Shuan Tong.Clinically,attention should be given to safety issues induced by interactions.