非維生素K拮抗劑口服抗凝血劑發生出血併發症對處方持續性的影響

The Impact of Bleeding Complications on Prescription Persistence of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs)

此研究藉由病歷回顧方式，分析心房纖維顫動（atrial fibrillation, AF）病人投與apixaban、dabigatran及rivaroxaban三種非維生素K拮抗劑口服抗凝血劑（non-vitamin K antagonist oral anticoagulants, NOACs）2年內中斷用藥原因，發生出血副作用對於處方持續性的影響。研究發現，出血副作用為中斷用藥因素，在apixaban、dabigatran、rivaroxaban組分別為22.2％、26.7％、25.0％。發生重大出血的部位為顱內出血（intracranial hemorrhage, ICH）及胃腸出血，個案人數apixaban有7位（皆為胃腸出血），dabigatran 10位（1位ICH，9位胃腸出血），rivaroxaban 9位（3位ICH，6位胃腸出血），4位ICH個案治療結果皆死亡。出血個案臨床特徵，dabigatran出血個案有年齡較高趨勢，重大出血、輕微出血及未出血組三組平均年齡分別為81.5±5.6、75.1±10.5及71.7±9.6歲（p＜0.05）；估算的腎絲球過濾率較低，三組平均值分別為38.8±12.7、56.3±14.5及63.0±6.1 ml／min／1.73m^2（p＜0.05）；女性發生比率較高，三組女性分布比率分別為60.6％、58.1％及34.5％（p＜0.05）。發生出血後用藥分析，多數個案仍會持續使用NOACs（重大出血：apixaban組71.4％、dabigatran組60.0％、rivaroxaban組44.4％；輕微出血：apixaban組83.3％、dabigatran組74.2％、rivaroxaban組64.7％），用藥方式包括維持原處方、降低原使用劑量或變更為其他NOACs。未持續使用NOACs，則將用藥轉換為warfarin、抗血小板製劑或長期停用所有抗血栓藥物。因發生出血而未繼續使用抗凝血劑個案，其平均CHA_2DS_2-VASc分數為3分以上，考量中風風險，停藥適宜性即有檢討之必要。

We conducted a chart review study to analyze the reasons of interrupting medications in atrial fibrillation patients who took non-vitamin K antagonist oral anticoagulants (NOACs)-apixaban, dabigatran and rivaroxaban during 2 years, and the impact of bleeding side effects on prescription persistence of NOACs. We found that the ratios of bleeding side effects as the reason of interrupting medications in apixaban, dabigatran and rivaroxaban group were 22.2%, 26.7%, 25.0% respectively. The occurrences of major bleeding events were intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding. There were 7 major bleeding cases in apixaban group (all GI bleeding), 10 in dabigatran (1 ICH, 9 GI bleeding) and 9 in rivaroxaban (3 ICH, 6 GI bleeding), the therapeutic outcomes of all the ICH cases were death. The clinical characteristics of dabigatran bleeding cases were older age [the mean age of major bleeding, minor bleeding and non-bleeding group were 81.5±5.6, 75.5.1±10.5 and 71.7±9.6 years (p ＜0.05)]; lower eGFR[ 38.8±12.7, 56.3±14.5 and 63.0±6.1 ml/min/1.73m^2 (p ＜0.05)] and female predominance[60.6%, 58.1% and 34.5% (p ＜0.05)]. After bleeding events, most patients took NOACs continuously (major bleeding: apixaban group 71.4%, dabigatran group 60.0%, rivaroxaban group 44.4%; minor bleeding: apixaban group 83.3%, dabigatran group 74.2%, rivaroxaban group 64.7%), including maintaining the original prescriptions, lowering doses or changing to other NOACs, some cases changed medications from NOACs to warfarin or antiplatelet agents and some discontinued all antithrombotic drugs. The cases who discontinued anticoagulants after bleeding events had average CHA_2DS_2-VASc score of more than 3. In consideration of the stroke risk, it is necessary to review the appropriateness of discontinuing drugs.