第二型糖尿病人使用Saxagliptin 在心腦血管事件的評估

The risk of cardio-cerebral vascular events in type 2 diabetes patients with the usage of saxagliptin

王子誠(ZI-Chen Wang)

指導教授 ： 吳寶珠

共同指導教授 ： 林佩津(Pei-Chin Lin)

高雄醫學大學/藥學院/藥學系碩士在職專班/碩士(2016年)

摘要

研究背景：
Saxagliptin為一藉抑制腸秘素(Incretins)代謝而達成控制血糖為目的的藥物。近年有文獻顯示長期使用會增加發生心血管事件的風險。本研究旨在利用整合分析評估從未接受過降血糖藥物saxagliptin的病人使用後產生心腦血管事件的風險及探討發生相關事件之危險因子。
研究方法：
本研究分為兩部分進行探討，第一部分採用文獻回顧及統合分析，搜尋電子資料庫尋找saxagliptin在心腦血管事件的相關研究。第二部分進行回溯性世代研究，根據南部某醫學中心之病歷資料，搜尋病人基本資料、用藥紀錄、檢驗數據及診斷紀錄，評估使用saxagliptin病人發生心腦血管副作用相關危險因子。
研究結果：
第一部分系統性文獻回顧及統合分析共納入6篇隨機對照文獻，根據分析結果，使用saxagliptin的病人與使用安慰劑的病人相比較，在心臟衰竭副作用有增加趨勢，相對風險為1.25(95%CI：1.05-1.48；p value=0.01)，使用藥物後並不會增加發生心肌梗塞及心絞痛的風險，次族群分析將具心血管相關病史者作分析，saxagliptin與安慰劑相比，具有病史者會增加發生心臟衰竭的風險，相對風險為1.26(95%CI：1.06-1.49；p value=0.009)。第二部分在回溯性世代研究，評估了使用saxagliptin的病人發生心腦血管相關事件的相關危險因子，結果顯示發生心腦血管相關事件主要因素為具有心臟衰竭病史的病人，其風險比為(OR=3.395, 95%CI: 1.118-10.305; p value=0.031)以及具有粥狀動脈硬化相關病史的病人，其風險比為(OR=2.936, 95%CI： 1.017-8.481； p value=0.047)。
研究結論：
依本研究結果顯示若為心血管高風險族群使用saxaglipltin會增加產生心腦血管事件的風險，且病人本身若有心臟衰竭及粥狀動脈病史為產生副作用的重要因子，因此使用藥物時評估病人心腦血管病史是有其必要性。

關鍵字

saxagliptin ； DPP-4 inhibitor ； 心腦血管相關事件 ； 系統性文獻回顧 ； 統合分析

並列摘要

Background:
Saxagliptin is an oral hypoglycemic agent that can control blood sugar by inhibiting the metabolism of incretin. Several research studies recently showed that saxagliptin may increase the risk of cardiovascular events recetently. The aims of our study were to evaluate the risk of cardio-cerebral vascular events in patients who received saxagliptin and explore the precipitating risk factors of cardio-cerebral vascular events.
Methods:
There were two parts in our study. First, a systemic review and meta-analysis of randomized controlled studies of comparing saxagliptin to placebo with cardio-cerebral vascular events was conducted. Databases were searched for relevant published articles. Second, a retrospective cohort study was performed based on medical records of a medical center in southern Taiwan. Data such as patient’s basic information, medication records, lab data and diagnostic records were extracted and used to explore the risk factors of cardio-cerebral vascular events.
Results:
Six randomized controlled studies were included in the meta-analysis. Compared to control, treatment with saxagliptin significantly increased the risk of heart failure (RR=1.25, 95%CI：1.05-1.48；p value=0.01). Saxagliptin did not increase the risk of myocardial infarction and angina. The result of subgroup stratified by cardiovascular history showed that treatment with saxagliptin increased risk of heart failure (RR=1.26, 95%CI：1.06-1.49；p value=0.009) in the subgroup with CV history. Retrospective cohort study explored the significant risk factors of developing cardio-cerebral vascular events in patients who used saxagliptin were heart failure history (OR=3.395, 95%CI：1.118-10.305；p value=0.031) and atherosclerosis disease history OR=2.936, 95%CI： 1.017-8.481; p value=0.047).
Conclusions:
Our study showed that the usage of saxagliptin may increase the risk of heart failure in type 2 diabetes patients with history of cardiovascular disease. We found that the heart failure history and atherosclerosis disease history were important risk factors for developing cardio-cerebral vascular events.

並列關鍵字

saxagliptin ； DPP-4 inhibitor ； cardio-cerebral vascular event ； meta-analysis

參考文獻

1. 邵愛玫. 建立藥師在門診第 2 型糖尿病患的藥事照護模式. 成功大學臨床藥學研究所學位論文 2002:1-203.

2. Turner RC, Cull CA, Frighi V, Holman RR, Group UPDS. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). Jama 1999;281:2005-12.

3. Huang ES, Basu A, O'Grady M, Capretta JC. Projecting the future diabetes population size and related costs for the U.S. Diabetes care 2009;32:2225-9.

4. Ryskjaer J, Deacon CF, Carr RD, et al. Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbAlc levels, but is not acutely affected by food intake. European journal of endocrinology / European Federation of Endocrine Societies 2006;155:485-93.

5. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care 2012;35:1364-79.