消化道潰瘍之高血壓長者是否要續用次級預防 之抗血小板藥物？ 以多中心世代研究衡量心血管保護效果與消化道出血風險

Antiplatelet Therapy for Secondary Prevention of Stroke in Hypertensive Elderly Patients with History of Peptic Ulcer Disease: A Multicenter Cohort Study

背景/目的：阿斯匹林(Aspirin)被用來當作心血管疾病的次級預防治療，但目前特別針對老人族群的阿斯匹林使用實證和指引並未完全建立。若產生消化性潰瘍之高血壓長者，尚未有研究去探討出血後繼續使用阿斯匹林之適切性，本研究將探討上消化道出血後，高血壓長者若持續使用阿斯匹林後續產生主要心腦血管事件及上消化道出血住院的相關性。

方法：本研究設計擬以回溯性世代研究的方式，於台大醫院及其分院資料庫作為研究資料來源。申請臺大醫療體系醫療整合資料庫，日期自2014年1月1日至2018年12月31日，當中有使用阿斯匹林且做胃鏡之65歲以上高血壓病人。分三組進行前瞻性追蹤（病歷回溯日期範圍自2014年1月1日至2020年12月31日），分別為停止使用阿斯匹林組、續用阿斯匹林組、轉換成Clopidogrel組，主要預後為主要腦心血管事件、上消化道出血住院。分析方式包括Cox比例風險模型、治療權重倒數機率。

結果：共735位病人納入分析，平均追蹤時間為39.7個月，共140人發生腦心血管事件。轉換成Clopidogrel組(n=88)並未發現減少主要腦心血管事件(adjusted HR 1.09, 95% CI 0.63-1.87)，且續用阿斯匹林組(n=210)增加主要腦心血管事件發生(adjusted HR 1.58, 95% CI 1.04-2.38)，相對於停止使用阿斯匹林組(n=172)。在後續上消化道出血住院的風險，轉換成Clopidogrel組(adjusted HR 1.07, 95% CI 0.48-2.37)和續用阿斯匹林組(adjusted HR 1.14, 95% CI 0.61-2.10)都沒有增加，但在次族群分析當中，慢性腎病病人有較高風險產生後續上消化道出血住院(adjusted HR 2.41, 95% CI 1.30-4.47)。

結論：此研究發現使用阿斯匹林之老年高血壓病人若因消化道潰瘍出血，後續續用阿斯匹林作為次級預防，並未減少心血管事件發生。抗血小板藥物作為老年高血壓病人之次級預防的適切性在消化道潰瘍發生後更應小心評估，尤其是在慢性腎病的共病下，可能會增加後續產生上消化道出血住院之風險。

 

Objectives: The cardiovascular and bleeding outcomes of antiplatelet therapy continuation in older hypertensive adults with peptic ulcer disease (PUD) are uncertain. We aimed to investigate the appropriateness of maintaining antiplatelet therapy in older hypertensive aspirin users with PUD by determining the risks of major adverse cardiac events (MACEs) and hospitalizations for upper gastrointestinal bleeding (hUGIBs).

Methods: This multicenter cohort study screened patients with panendoscopy-proven PUD and hypertension aged 65 years or older between 2014 and 2018. Subsequent antiplatelet strategies were categorized as aspirin discontinuation (AD), aspirin continuation (AC), and switch to clopidogrel (SC) groups. Inverse probability of treatment weighting was applied. The main outcomes were incident MACEs and hUGIBs, followed through 31 December 2020.

Results: 735 eligible patients were analyzed. During a median follow-up of 39.7 months, 140 MACEs occurred. Compared with AD, AC increased the risk of incident MACEs (adjusted HR 1.58, 95% CI 1.04-2.38) in secondary prevention patients. On the other hand, 102 hUGIBs occurred during a median follow-up of 43.4 months. Compared with AD, neither AC nor SC affected the risk of hUGIBs in secondary prevention patients. However, secondary prevention patients with chronic kidney disease were at increased risk of hUGIBs (adjusted HR 2.41, 95% CI 1.30-4.47).

Conclusions: AC did not reduce MACEs in older hypertensive adults with PUD previously taking aspirin for secondary prevention. We do not advocate continuing antiplatelet therapy in older hypertensive adults once with PUD, despite its neutral association with hUGIBs.