医药新知【44】

1、醫藥新知【44】 公告日期: 摘錄藥師: 黃子芸¡ 主題:Raloxifene May Not Signficantly Affect Heart Disease RiskRaloxifene不會顯著影響心臟疾病的危險性¡ 內容摘要：July 12, 2006 Raloxifene has no effect on heart disease but reduces the risk for breast cancer and vertebral fracture, although it increases the risk for thromboembolism and

2、 stroke, according to the results of a randomized study reported in the July 13 issue of The New England Journal of Medicine."The effect of raloxifene, a selective estrogen-receptor modulator, on coronary heart disease (CHD) and breast cancer is not established," write Elizabeth Barrett-Co

3、nnor, MD, from the University of California, San Diego, and colleagues from the Raloxifene Use for The Heart (RUTH) Trial Investigators. "Raloxifene therapy has been associated with improvement in the levels of serum lipoprotein cholesterol, fibrinogen, and homocysteine. The favorable effect of

4、 raloxifene on markers of cardiovascular risk, coupled with evidence from observational studies that treatment with estrogen was associated with a reduced risk of coronary heart disease (CHD) in postmenopausal women, led to the design of the RUTH trial to determine the effect of raloxifene on clinic

5、al coronary events."The investigators randomized 10,101 postmenopausal women (mean age, 67.5 years) with CHD or multiple risk factors for CHD to receive 60 mg of raloxifene daily or placebo. Median follow-up was 5.6 years. The 2 main endpoints were coronary events, defined as death from coronar

6、y causes, myocardial infarction, or hospitalization for an acute coronary syndrome; and invasive breast cancer.Compared with placebo, raloxifene had no significant effect on the risk for primary coronary events (533 vs 553 events; hazard ratio HR, 0.95; 95% confidence interval CI, 0.84 - 1.07). Howe

7、ver, it was associated with lower risk for invasive breast cancer (40 vs 70 events; HR, 0.56; 95% CI, 0.38 - 0.83; absolute risk reduction, 1.2 invasive breast cancers per 1000 women treated for 1 year). This benefit was primarily accounted for by a reduced risk for estrogen-receptorpositive invasiv

8、e breast cancers.The rates of death from any cause or total stroke were not significantly different between groups. However, raloxifene was associated with an increased risk for fatal stroke (59 vs 39 events; HR, 1.49; 95% CI, 1.00 - 2.24; absolute risk increase, 0.7 per 1000 woman-years) and venous

9、 thromboembolism (103 vs 71 events; HR, 1.44; 95% CI, 1.06 - 1.95; absolute risk increase, 1.2 per 1000 woman-years). Raloxifene was associated with reduced risk for clinical vertebral fractures (64 vs 97 events; HR, 0.65; 95% CI, 0.47 - 0.89; absolute risk reduction, 1.3 per 1000)."In postmeno

10、pausal women with CHD or at increased risk for CHD, treatment with raloxifene for a median of 5.6 years reduced the risk of invasive breast cancer and did not change the incidence of coronary events," the authors write. "In these women, the difference in the absolute rates of events that w

11、ere decreased (i.e., breast cancer and clinical vertebral fractures) was similar to the difference in the absolute rates of events that were increased (i.e., venous thromboembolic events and fatal strokes). When considering the use of raloxifene in a postmenopausal woman, the clinician should take i

12、nto account the individual woman's risk of disease and her personal preferences and weigh potential benefits against risks and against the availability of alternative interventions."¡中文摘要：2006年7月12日，根據發表於7月13日 The New England Journal of Medicine期刊上的研究報告顯示，Raloxifene雖然增加血栓和中風的危險性，但沒有明顯影

13、響心臟疾病，且降低罹患乳癌和脊椎壓迫性骨折的風險。 美國加州大學聖地牙哥醫學院的Elizazbeth Barrett-Connor醫師與使用Raloxifene 對心臟作用之臨床試驗( RUTH )的研究團隊，依據所發表的研究報告指出Raloxifene是一種選擇性雌性激素受體調節劑，對於冠狀動脈心臟疾病及乳癌的影響尚未被建立。已有研究結果發現使用raloxifene治療可以改善lipoprotein cholesterol, fibrinogen和homocysteine的血中濃度，而減少心血管疾病危險因子的產生，另外也有證據顯示雌性激素用於停經後婦女可以降低罹患冠狀動脈心臟疾病的危險，於是

14、設計RUTH臨床試驗來評估raloxifene對於冠狀動脈疾病的影響。 作者隨機納入了10101位有心血管疾病或是有多重心血管疾病危險因子的停經後婦女 ( 平均年齡為67.5歲 )，每天給予60 mg raloxifene或安慰劑治療並進行評估5.6年。二個主要評估的指標是冠狀動脈疾病的發生事件，其定義為因冠狀動脈疾病、心肌梗塞造成死亡或是因急性冠狀動脈徵後群導致住院，與產生侵犯性乳癌。 和安慰劑比較，raloxifene對於產生冠狀動脈事件的危險沒有顯著影響 ( 533 vs. 553事件; 風險比, 0.95; 95% CI, 0.84-1.07 )，但會降低罹患侵犯性乳癌的危險 ( 40

15、 vs. 70事件; 風險比，0.56; 95% CI, .83; 每1000位婦女治療一年可以降低1.2個案例產生侵犯性乳癌 )，主要是減少雌性激素受體陽性侵犯性乳癌的危險。總死亡率或是中風的死亡率，raloxifene和安慰劑並沒有顯著差異，而raloxifene卻會增加致命性中風 ( 59 vs. 39事件; 風險比, 1.49; 95% CI, 1.00-2.24; 每1000位婦女治療一年會增加0.7個案例產生致命性中風 )與靜脈血栓的危險 (103 vs. 71事件; 風險比, 1.44; 95%CI, 1.06-1.95; 每1000位婦女治療一年會增加1.2個案例產生靜脈血栓 )。另外raloxifene可以減少脊椎壓迫性骨折的危險 ( 64 vs. 97事件; 風險比, 0.65; 95% CI, 0.47-0.89; 每1000位婦女將減少1.3個案例產生脊椎壓迫性骨折 )。 Raloxife