事与愿违的大型临床试验结果告诉了我们什麽.ppt

WhatWehaveLearnedfromtheFailureofLargeClinicalTrials?

事与愿违的大型临床试验结果告诉了我们什麽?

HUIRutai惠汝太

BeijingFuWaiHospital,China

北京阜外医院高血压中心主任

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WomensHealthInitiativeRCTrevealedthathormone-replacementtherapy,whichreducesLDLcholesterollevels,increasedtheriskofcardiovasculardisease.

(Andersonetal.Effectsofconjugatedequineestrogeninpostmenopausalwomenwithhysterectomy:theWomensHealthInitiativeRandomizedControlledTrial.JAMA2004;291:1701-1712);ENHANCE;

ENHANCEshowedthatezetimibedidnotreducetheprogressionofarteriosclerosiswhencombinedwithsimvastatin,ascomparedwithsimvastatinalone,eventhoughthecombinationdidresultinagreaterreductionofLDLcholesterol.

Kasteleinetal:NEJM2008,358:1431-1443;

Correction:NEJM2008,358:1977;Post-trialStudy;;Follow-up10years

Sulfonylurea-InsulinMetoformin

AnyDM-related

Endpoints9%(P=0.04)21%(P=0.01)

MicrovasDis24%(P=0.001)

MI15%(P=0.01)33%(P=0.005)

Deathfrom

Anycause13%(P=0.007)27%(P=0.002)

与传统限制饮食治疗比较，药物强化治疗

HolmanetalNEJM2008:359:;ADVANCE;ADVANCE;ADVANCE;ADVANCE;Meta-analysis：

Rosiglitazone（Avandia）;Meta-analysis：

Rosiglitazone（Avandia）;Meta-analysis：Rosiglitazone（Avandia）

Rosiglitazoneimprovesglucosecontrol,butitmayalsobeassociatedwithincreasedcardiovascularrisk.

(Nissenetal.Effectofrosiglitazoneontheriskofmyocardialinfarctionanddeathfromcardiovascularcauses.NEnglJMed2007;356:2457-2471);ONTARGET;ONTARGET;Results;Kaplan–MeierCurvesforthePrimaryOutcomeintheThreeStudyGroups.;Telmisartanwasequivalenttoramiprilinpatientswithvasculardiseaseorhigh-riskdiabetesandwasassociatedwithlessangioedema.

Addinganang