Effect of Cox-II inhibitor on biochemical markers in cardiovascular-related adverse effects

Abstract

The selective cyclooxygenase-2 (COX-2) inhibitors have been associated with increased cardiovascular risk. The goal of the present study was to investigate the impacts of COX-2 inhibitors on biochemical indices in cardiovascular disease. We studied the effects of Cox-II inhibitor using experimentally induced hyperlipidemic rats. Plasma total cholesterol, LDL and triglyceride concentrations will be determined before and after animals treated with cyclooxygenase-2 (COX-2) inhibitors. Biochemical markers related to cardiovascular events including prostaglandin I2, thromboxaneA2 and others will also be investigated. We also investigated these biochemical markers in patients taking Celebrex and NSAIDs. We hope these studies will reveal clinically useful biochemical markers for cardiovascular events in patients taking Cox-II inhibitor. Study found that animals fed a normal diet and high fat diet rats, the blood will vote for Celebrex in the Hs-CRP concentrations decreased. Clinical trials found that subjects with serum homocysteine concentration and whether or not the use of Methotrexate, Prednisolone, Sulfasalazin and Hydroxychlorquine on blood homocysteine no significant impact. Subjects taking Celebrex would reduce the concentration of blood triglyceride; Celebrex combined Prednisolone measured by the use of lead in blood to increase HDL concentration; Celebrex combined Hydroxychlorquine use, will be reduced by the measured blood LDL, TC concentrations; Celebrex Prednisolone combined MTX and blood will be tested in the concentration of HDL increased, Celebrex as disease modifying anti-rheumatic drug type of diversity, no significant lipid concentration differences. We hope these studies will reveal clinically useful biochemical markers for cardiovascular events in patients taking Cox-II inhibitor.

第二環氧酶抑制劑 (Cyclooxygenase II inhibitor, Cox-II inhibitor) 屬於非類固醇類抗發炎藥物的一種，其主要是抑制調控發炎作用和造成疼痛的前列腺素之合成。目前在台灣臨床上使用Cox-II 抑制劑止痛藥之最大族群之一是慢性關節炎病患，主要用於緩解發炎與疼痛。然而在2004年美國一項為期三年的的隨機對照臨床研究中卻發現服用 rofecoxib的患者其產生心血管不良反應的危險性明顯高於對照組，因而造成此藥全球性下市。至於另一被普遍使用之 Cox-II 抑制劑止痛藥 Celebrex是否確實會直接增加心血管副作用的危險性仍未有定論。國內外多項研究顯示Cox-II 抑制劑對不同心血管副作用的相關危險因子所產生之影響有顯著不同。本研究收錄使用及未使用Cox-II 抑制劑Celebrex之病患為臨床研究對象，檢測其血中各脂質代謝相關生化值及心血管病變相關之危險因子。同時也進行動物研究探討正常及高血脂之動物，投予 Celebrex 及非Cox-II抑制劑 Naproxan前後，其血中各脂質代謝相關生化值及心血管病變相關危險因子之變化情形。 動物研究發現餵食正常飲食與高油脂飲食大鼠，血脂無明顯的影響；但投予Celebrex會使血中Hs-CRP濃度下降。臨床觀察發現受測者血中同半胱胺酸濃度與有無使用疾病修飾型抗風濕藥物無明顯相關；服用Celebrex受測者會降低血中三酸甘油脂的濃度；Celebrex合併Prednisolone使用會使受測者血中的HDL濃度增加；Celebrex合併Hydroxychlorquine使用，會降低受測者血中LDL、TC濃度；Celebrex合併MTX及Prednisolone會使受測者血中的HDL濃度增加，但Celebrex隨著疾病修飾型抗風濕藥物種類的多樣性，血脂濃度無顯著上的差異。 第二環氧化酶抑制劑止痛藥對心血管疾病危險因子相關生化指標仍無法綜合判定。