课件：NSAIDs相关性溃疡的防治现状.ppt

NSAIDs相关性溃疡的防治现状,张 世 能,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 的新安全措施。 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应-25% 长期服用导致溃疡-15%30% 美国每年治疗NSAIDs胃肠道不良反应费用- 40亿美元,Singh. Am J Med. 1998;105(suppl 1B):31S-38S. Johnson et al. Pharmacoeconomics. 1997;12:76-88.,NSAIDs胃肠道不良反应发生率、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需要0.35美元额外支出防治胃肠道不良 反应 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 99,0.36,0.28,0.20,0.024,0.011,0.005,Annual risk of death (%),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 直接渗透 全身作用 促进炎症反应 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相关性溃疡报警症状,Incidence of Endoscopic NSAIDs-Induced Ulceration,Mean Range 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 Photograph of Gastric Ulcer,停用或减用NSAIDs 识别、避免和减低危险因素 根除 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,2.6,5.6,2.2 - 2.9,4.4 - 7.0,Sorensen et al, Am J Gastroenterol 2000; 95; 2218,Risk of Combining Low-Dose Aspirin with NSAIDs,根除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,P=0.024,常规剂量H2RA不能预防NSAIDs性胃溃疡,2019/8/7,20,可编辑,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,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,Endpoint serious GI complications,Relative risk reduction 40% p-value 0.049,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%,P=0.09,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 r