NSAIDs相关性溃疡的防治现状

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,NSAIDs相关性溃疡的防治现状,FDA NEWS,年月日，美国食品与药物管理局,公布了一系列与非甾体类抗炎药s相关,的新平安措施。,宣布，已上市的都必须在其说明书上,注明“具有增加心血管事件和胃肠道出血危险的警告。,此次列出的名单不但包括了此前争议,颇多的环氧合酶抑制剂，而且涵盖,了所有处方药和非处方药范畴的非选择性。,流行病学, 全球每天使用NSAIDs者-3 000万人, 美国每年使用NSAIDs处方数-1亿张,总销售额-7亿美元, 约70%老年人每周使用NSAIDs一次以上,其中每天使用者-34%, 使用NSAIDs人群出现胃肠道不良反响-25%,长期服用导致溃疡-15%30%, 美国每年治疗NSAIDs胃肠道不良反响费用-,40亿美元,Singh.,Am J Med,. 1998;105(suppl 1B):31S-38S.,Johnson et al.,Pharmacoeconomics.,1997;12:76-88.,NSAIDs胃肠道不良反响发生率、死亡率和费用-美国资料,每年因此住院者: 107,000,总住院费用 ($12,500/每人次): 14亿美元,年死亡人数: 16,500,1美元NSAIDs,反响,因NSAIDs胃肠道偶发事件，每次支出$2,172 ( 1992年),美国常见死因比较,Singh et al.,J Rheumatol,99,0.00,0.15,0.10,0.05,0.20,0.35,0.30,0.25,0.40,Annual risk of death (%),Cigarette smoking,Cancer,NSAID use,Motor car accident,Home accident,Airplane crash,(frequent flyer),Fries.,AM J Med,1991; Wilson, Crouch.,Science,1987,Mortality from NSAIDs versus other causes,发病机制, 直接损害胃肠粘膜, 抑制环氧合酶(COX),抑制黏膜前列腺素(PG)合成,直接浸透,全身作用, 促进炎症反响, 影响细胞增生和凋亡, 导致胃肠动力异常,Singh et al. Arch Intern Med 96,Dyspepsia +,Dyspepsia -,N = 1921,81%,19%,NSAIDs相关性溃疡报警病症,Incidence of EndoscopicNSAIDs-Induced Ulceration,MeanRange,NSAIDs Gastropathy 90 %,Gastric Ulcer 15 %10 to 30%,Duodenal Ulcer 5 % 4 to 10 %,Wolfe MM et al. N Engl J Med 1999;340:1888-1899,Endoscopic Photograph of Gastropathy,Endoscopic Photographof Gastric Ulcer,停用或减用NSAIDs,识别、防止和减低危险因素,铲除 H. pylori,抗溃疡药物,H2RA, misoprostol, PPI,选用选择性COX-2 抑制剂,NSAIDs相关性溃疡防治措施,NSAIDs-induced Ulcer prevention should be based on risk factors rather than symptoms,NSAIDs 致胃肠道不良作用的危险因素,Aspirin剂量与溃疡出血危险度,Aspirin Dose,75 mg (n=27),150 mg (n=22),300 mg (n=62),Odds Ratio (95% Cl),2.3 (1.2-4.4),3.2 (1.7-6.5),3.9 (2.5-6.3),Weil J et al.,BMJ.,1995;310:827-830,.,National cohort study in Denmark,27,694 people on aspirin 100-150 mg qd,Treatment regimen,Increased incidence,over general,population,95% CI,Low-dose aspirin,Low-dose aspirin + NSAIDs,Sorensen et al, Am J Gastroenterol 2000; 95; 2218,Risk of Combining Low-Dose Aspirin with NSAIDs,铲除Hp可降低NSAIDs溃疡危险度,Naproxen 750 mg/d for 8 wks,Diclofenac SR 1000 mg/d for 26 wks,Chan et al.,Lancet,2002,Ulcer at 8 wk %,Ehsanullah et al. BMJ 1988,NSAID + Ranitidine 150 mg b.i.d.,N=263,NSAID + Placebo,常规剂量H2RA不能预防NSAIDs性胃溃疡,Taha et al. NEJM 1996,N=285,OGD,Week,0,24,4,8,NSAID + Placebo,NSAID + Famotidine 40 mg/d,NSAID + Famotidine 80 mg/d,0,5,10,15,20,25,Famotidine 80,Famotidine 40,Placebo,GU,DU,24-wk,ulcer,%,P=0.03,大剂量,Famotidine,预防NSAIDs相关性溃疡,MUCOSA Study,NSAID + Misoprostol 800,g/d,N=8843,Week,0,24,NSAID + placebo,Endpointserious GI complications,Relative risk reduction40%,Silverstein et al.,Ann Intern Med,95,*Dropout rate 27.5%,due to GI side effects,Number needed to treat (NNT) = 264,COX抑制剂：CLASS study,Endpoint: ulcer complications,Silverstein et al. JAMA 2000,11/ 1441,20/ 1384,1.45%,0.76%,event per patient-year of exposure,Arthritis,(RA),Rofecoxib 50 mg QD,Naproxen 500 mg BID,N = 8076,Month 0 1 2 3 4 5 6 7 8 9 10 11 12,VIGOR study,Endpoint: Clinical upper GI events,Coxib vs. NSAIDs+PPI for high-risk patients,Celecoxib 200 mg bid + omeprazole placebo od,Diclofenac 75 mg bid + omeprazole 20 mg od,Inclusion,NSAID-related ulcer bleed; and,Healed ulcer before randomization; and,HP-,or,HP,eradicated,Randomization (double blinded, randomized study),Endpoints,Primary:,recurrent ulcer bleed at 6 months,Secondary:,recurrent endoscopic ulcers at 6 months,Chan et al. Gastroenterology 2004 (in press),PPI plus COX-2 inhibitor offers the best GI protection?,Ulcer incidence at 6 months by NSAIDs type,*,P,.01, *,P,.001, *,P,.0001,vs,. placebo.,*,*,*,*,134,141,125,318,326,334,n=,Scheiman et al.,DDW,2004,Coxib plus PPI,High-risk,(Prior ulcer complication,3 risk factors, or,concomitant aspirin),NSAID plus PPI; or,2. Coxib,Moderate-risk,(1 2 risk factors),Least ulcerogenic NSAIDs,at lowest effective doses,Low-risk,(No risk factor),Recommendations,Risk assessment,小 结,NSAIDs相关性溃疡发生率高、治疗费用宏大；,选择性COX-2抑制剂致胃肠道不良作用较低；,NSAIDs相关性溃疡临床报警病症少；,NSAIDs相关性溃疡预防应高度重视其危险因素；,防治NSAIDs相关性溃疡以PPI最为有效；,对存在高危因素的NSAIDs相关性溃疡，可选择,选择性COX2抑制剂+PPI。,谢谢！,谢谢大家！,结 语,