非瓣膜性心房顫動病人使用新型抗凝血劑現況及成效分析

Abstract

背景:近年來新型口服抗凝血劑(NOAC)開始應用於非瓣膜性心房顫動的病人來預 防中風,然而在臨床應用的療效及安全性仍是需進一步研究的議題。 目的:分析新型口服抗凝血劑開始應用於台灣後,影響整體抗血栓藥物的開方結構 及應用於臨床上的療效及安全性。 方法: 利用台灣健保資料庫分析從 2012 年 6 月至 2015 年 12 月使用 dabigatran、 rivaroxaban 或 warfarin 的心房顫動的病人。我們利用傾向分數配對的方法來平衡 兩個分析的族群,及利用 Cox 比例風險模式來計算兩個分析族群間發生事件的風 險。我們分析病人直到最早的事件發生、停藥、換藥或 2015 年 12 月的最後一天。 結果: 相較於 warfarin,NOAC 有比較低的顱內出血(HR: 0.45, 95% CI: 0.31-0.66) 、 靜脈栓塞(HR: 0.37, 95% CI: 0.21-0.66)、及綜合出血(HR: 0.8, 95% CI: 0.69-0.92)風 險。然而,腸胃道出血的出血在兩組之間則沒有顯著的差異。在次群組分析中, rivaroxaban 20 毫克及 15 毫克相較於 warfarin 有較低的缺血性中風的風險,而我們 在 rivaroaban 20 毫克亦發現其腸胃道出血的風險較 warfarin 來得低(HR:0.47, 95% CI: 0.24-0.90)。Rivaroxaban 應用在 65 歲及 80 歲以上的老人相較於 warfarin,其預 防缺血性中風的效果較佳。 結論: 新型口服抗凝血劑相較於 warfarin 有較低的顱內出血的風險。另外, rivaroxaban 的劑量或許需大於 15 毫克以上才是預防缺血性中風的有效劑量。再者, rivaroxaban 在老年族群中相較於 warfarin 可能是比較好的選擇。

Background: Novel oral anticoagulants (NOACs) recently launched to Taiwan for preventing ischemic stroke among non-vavluar atrial fibrillation patients. However, the effectiveness and safety in real-world clinical practice is still scarce, especially in Asian population. Objective: First, to analyze the prescription patterns of oral antithrombotic agents after the launch of NOACs. Second, to assess the effectiveness and safety between patients who newly initiated NOAC and warfarin among Asian population. Third, we aim to evaluate whether being long-term prescribed warfarin would affect the effectiveness and safety of NOAC. Methods: We used National Health Insurance Research Database (NHIRD) to assess non-valvular atrial fibrillation patients who prescribed dabigatran, rivaroxaban, or warfarin from Jun 1st, 2012 to Dec 31th, 2015. We applied propensity score matching to the Cox proportional hazard model to evaluate the effectiveness and safety between NOACs (including dabigatran and rivaroxaban) and warfarin. The analyses were also repeated to assess different drug groups, dose groups, and elderly patients with at least 65 or 80 years old. The follow-up period was the time from index date to the outcome of interests, switching to or discontinuation of alternative oral anticoagulants, end of the administrative period. Results: Compared with warfarin in the warfarin-naive stratum, NOAC were generally associated with a lower risk of intracranial hemorrhage (HR: 0.45, 95% CI: 0.31-0.66), venous thromboembolism (HR: 0.37, 95% CI: 0.21-0.66), and the composite bleeding events (HR: 0.8, 95% CI: 0.69-0.92), whereas there were no significant differences in 3 the risk of gastrointestinal bleeding. In different dose groups, rivaroxaban 20 mg and 15 mg were associated with a lower risk of ischemic stroke compared with warfarin (HR:0.48, 95%: 0.29-0.80 and HR: 0.69, 95% CI: 0.53-0.90 in rivaroxaban 20 mg and 15 mg, respectively), and rivaroxaban 20 mg was associated with a lower risk of gastrointestinal bleeding (HR:0.47, 95% CI: 0.24-0.90). In elderly, rivaroxaban was associated with lower risk of ischemic stroke compared with warfarin in patients with at least 65 years old (HR: 0.71, 95% CI: 0.56-0.89) and 80 years old (HR: 0.65, 95% 0.46-0.61). In warfarin-experienced stratum, NOAC was associated with lower risk of intracranial hemorrhage (HR: 0.38, 95% CI: 0.19-0.78). However, there were no significant differences in the risk of ischemic stroke, transient ischemic attack, venous thromboembolism, and gastrointestinal bleeding. Conclusions: In the ─real-world∥ clinical practice, NOACs were generally associated with a lower risk of intracranial hemorrhage compared with warfarin. Rivaroxaban with a dose equal to or greater than 15 mg may be considered as a sufficient therapeutic dose in preventing thromboembolism events. Moreover, rivaroxaban was found to be a better choice than warfarin in preventing ischemic stroke among elderly patients.