非維他命K拮抗劑口服抗凝血劑在亞洲心房纖維顫動病人的使用評估

Evaluation of the Real-World Non-Vitamin K Antagonist Oral Anticoagulants Use in Asian Patients with Atrial Fibrillation

林欣儀(Shin-Yi Lin) ； 郭錦樺(Ching-Hua Kuo) ； 黃織芬(Chih-Fen Huang) ； 湯頌君(Sung-Chun Tang) ； 沈麗娟(Li-Jiuan Shen) ； 鄭建興(Jiann-Shing Jeng)

《台灣中風醫誌》 2卷3期 (2020/09) Pp. 206-212

https://doi.org/10.6318/FJS.202009_2(3).0002

摘要

非維他命K拮抗劑口服抗凝血劑（non-vitamin K antagonist oral anticoagulants﹝NOACs﹞）劑量固定、不須定期監測凝血功能，已被各國治療指引建議優先於warfarin，用以預防心房纖維顫動病人中風與全身性栓塞。我們透過回溯性資料分析NOACs臨床使用的療效與安全性，與大型臨床研究的結果比較，評估NOACs在亞洲族群的治療效益是否不同。接著我們試著建立標準化的NOACs血中濃度檢測流程，主要是常規的凝血功能測試與NOACs濃度的關聯性可信度不足。我們的先導試驗收案使用dabigatran的病人檢測濃度，發現用藥順服性不佳顯著提高濃度偏低的風險。進一步收案使用rivaroxaban與apixaban的病人檢測濃度，發現rivaroxaban相對apixaban較容易有濃度低於預期範圍的情形，且未依據仿單建議處方rivaroxaban劑量顯著提高濃度偏低的風險。我們團隊將持續針對NOACs藥物濃度的臨床應用及與臨床預後的連結進行相關研究，期許能找出亞洲人使用NOACs的可能濃度偏高的族群，以增加NOACs的療效及安全性。

並列摘要

Fixed dose non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over warfarin to prevent stroke and systemic embolism among patients with atrial fibrillation in practice guidelines across different countries. Unlike warfarin, routine coagulation tests are not necessary because of the wider therapeutic window for NOACs. Our research team has conducted retrospective studies to evaluate the efficactiveness and safety of NOACs in real-world, especially in Asian population. Because routine coagulation tests do not reliably correlate with NOACs drug concentration, we developed a standardized process to measure NOACs concentration. We first conducted a pilot study among patients under dabigatran treatment and our prospective data showed that low dabigatran concentration was associated with suboptimal dabigatran adherence. We further enrolled patients under rivaroxaban or apixaban treatment, and the results showed that rivaroxaban concentration were more likely to be lower than the expected range reported in clinical trials, in comparison to apixaban concentration. In addition, low rivaroxaban concentration was associated with inappropriately prescribed rivaroxaban dose. Our future direction is to continuously enroll and maintain the cohort of NOACs therapy to investigate the correlation between drug level and clinical outcomes. We will also focus on identifying specific populations that tend to have high NOACs drug levels. The results of our studies provide further improvement in the efficacy and safety of NOACs therapy.

並列關鍵字

atrial fibrillation ； ischemic stroke ； non-vitamin K antagonist oral anticoagulants