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,FDANEWS,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-3000万人美国每年使用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.AmJMed.1998;105(suppl1B):31S-38S.Johnsonetal.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:16,5001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,Singhetal.JRheumatol99,0.36,0.28,0.20,0.024,0.011,0.005,Annualriskofdeath(%),Fries.AMJMed1991;Wilson,Crouch.Science1987,MortalityfromNSAIDsversusothercauses,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,Singhetal.ArchInternMed96,Dyspepsia+,Dyspepsia-,N=1921,81%,19%,NSAIDs相关性溃疡报警症状,IncidenceofEndoscopicNSAIDs-InducedUlceration,MeanRangeNSAIDsGastropathy90%GastricUlcer15%10to30%DuodenalUlcer5%4to10%,WolfeMMetal.NEnglJMed1999;340:1888-1899,EndoscopicPhotographofGastropathy,EndoscopicPhotographofGastricUlcer,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-inducedUlcerpreventionshouldbebasedonriskfactorsratherthansymptoms,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,AspirinDose75mg(n=27)150mg(n=22)300mg(n=62),OddsRatio(95%Cl)2.3(1.2-4.4)3.2(1.7-6.5)3.9(2.5-6.3),WeilJetal.BMJ.1995;310:827-830.,NationalcohortstudyinDenmark27,694peopleonaspirin100-150mgqd,Treatmentregimen,Increasedincidenceovergeneralpopulation,95%CI,Low-doseaspirinLow-doseaspirin+NSAIDs,2.6,5.6,2.2-2.9,4.4-7.0,Sorensenetal,AmJGastroenterol2000;95;2218,RiskofCombiningLow-DoseAspirinwithNSAIDs,根除Hp可降低NSAIDs溃疡危险度,Naproxen750mg/dfor8wks,DiclofenacSR1000mg/dfor26wks,Chanetal.Lancet2002,Ulcerat8wk%,Ehsanullahetal.BMJ1988,P=0.024,常规剂量H2RA不能预防NSAIDs性胃溃疡,Tahaetal.NEJM1996,N=285,OGD,Week,0,24,4,8,NSAID+Placebo,NSAID+Famotidine40mg/d,NSAID+Famotidine80mg/d,大剂量Famotidine预防NSAIDs相关性溃疡,MUCOSAStudy,NSAID+Misoprostol800g/d,N=8843,Week,0,24,NSAID+placebo,EndpointseriousGIcomplications,Relativeriskreduction40%p-value0.049,Silversteinetal.AnnInternMed95,*Dropoutrate27.5%duetoGIsideeffects,Numberneededtotreat(NNT)=264,COX抑制剂：CLASSstudyEndpoint:ulcercomplications,Silversteinetal.JAMA2000,11/1441,20/1384,1.45%,0.76%,P=0.09,eventperpatient-yearofexposure,Arthritis(RA),Rofecoxib50mgQD,Naproxen500mgBID,N=8076,Month0123456789101112,VIGORstudyEndpoint:ClinicalupperGIevents,Coxibvs.NSAIDs+PPIforhigh-riskpatients,Celecoxib200mgbid+omeprazoleplacebood,Diclofenac75mgbid+omeprazole20mgod,InclusionNSAID-relatedulcerbleed;andHealedulcerbeforerandomization;andHP-orHPeradicated,Randomization(doubleblinded,randomizedstudy),EndpointsPrimary:recurrentulcerbleedat6monthsSecondary:recurrentendoscopiculcersat6months,Chanetal.Gastroenterology2004(inpress),PPIplusCOX-2inhibitoroffersthebestGIprotection?,Ulcerincidenceat6monthsbyNSAIDstype,*P.01,*P.001,*P.0001vs.placebo.,*,*,*,*,134,141,125,318,326,334,n=,Scheimanetal.DDW2004,CoxibplusPPI,High-risk(Priorulcercomplication,3riskfactors,orconcomitantaspirin),NSAIDplusPPI;or2.Coxib,Moderate-risk(12riskfactors),LeastulcerogenicNSAIDsatlowesteffectivedoses,Low-risk(Nor