第二型環氧酶抑制藥物新知－由coxibs心血管事故談起

New Approaches of Cyclooxygenase-2 Inhibitors-Cardiovascular Events of Coxibs

唐正乾(Chang-Chen Tang) ； 周立平(Lee-Pin Chou) ； 周昌樺(Chang-Hua Chou) ； 許世元(Shih-Yuan Hsu)

《內科學誌》 16卷4期 (2005/08) Pp. 153-161

https://doi.org/10.6314/JIMT.2005.16(4).01

摘要

最近數個針對「非固醇類抗發炎藥與結腸直腸息肉及結腸直腸腺瘤的預防」大型臨床研究的成果與資料陸續被披露或發表，其中rofecoxib與心血管疾病發作風險的分析顯示，長期高劑量的持續服藥，非致死型心肌梗塞與中風等之發作風險明顯增加，導致默克藥廠在2004年底宣佈將Vioxx(上標 ®)撤離市場。稍後，美國藥物食品檢驗局(FDA)在針對這一類藥品（傳統NSAIDs與coxibs）的使用，提出警語建議「醫師使用這類藥品時需評估病患個別潛在的心血管疾病危險因子，儘量使用最低有效劑量或考量替代治療方案」。在VIGOR及CLASS臨床研究中確認，使用coxibs較傳統NSAIDs發生潰瘍症狀、潰瘍併發症或其他腸胃道副作用的機率與嚴重度，減少一半左右。但在心血管事故風險兩者並無顯著差異性，甚至rofecoxib比naproxen有較高的心血管事故風險發生。雖然APPROVe及APC臨床研究指出，心血管事故風險與coxibs劑量高低有密切關聯，但目前證據顯示，COX-2及特定的前列腺素，高度的表現於某些消化系癌症（包括，大腸直腸癌、胃癌、食道癌等）及炎症反應（包括，疼痛反應、心血管病變及神經組織病變）。因此coxibs可能對這些疾病的治療有所助益，包括炎症反應的抑制、改善內皮依賴性血管擴張、神經細胞保護作用及結腸直腸腺瘤與阿滋海默症的預防。

關鍵字

第二型環氧酶抑制劑 ； coxib ； 非固醇類抗發炎藥 ； 心血管事故 ； 前列腺素 ； 環氧酶

並列摘要

Due to an increased risk of cardiovascular events in current users with high-dose rofecoxib among elderly patients. Rofecoxib was voluntarily withdrawn from the market at late 2004. Lately, FDA advises the use of the lowest effective dose of NSAIDs (including coxibs), if physicians determine that continued use is appropriate for individual patients. Two large trials (the CLASS study and the VIGOR study) appeared that coxibs reduced the risk of GI toxicity (associated with a significantly incidence of upper GI bleeding, perforation or ulceration and symptomatic ulcers), but there were no differences in the risk of myocardial infarction and stroke events, compared with traditional NSAIDs for the treatment of pain and inflammatory conditions. Even coxibs use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. In light of recent reports of cardiovascular harm associated with treatment with other agents in both APPROVe and APC trial. The available data show that coxibs appears to play an important role in the modulation of intestinal polyposis and colorectal carcinogenesis. Additionally, COX-2 expression may be associated with inflammatory responses leading to the occurrence of Alzheimer's disease and potentially, coxibs could be used to retard the progression of this condition.

並列關鍵字

COX-2 inhibitor ； Coxib ； NSAID ； CV event ； Prostaglandin ； COX