（英文原文）TrialSummaryAleCardioDescription:Thegoalofthetrialwastoevaluatetreatmentwiththeperoxisomeproliferator-activatedreceptor(PPAR)dual-agonistaleglitazarcomparedwithplaceboamongtype2diabeticpatientshospitalizedforanacutecoronarysyndrome.AleglitazarisadualagonistofPPAR-αand-γreceptors.TheprimaryeffectofPPAR-αactivationistoimproveplasmalipidprofile,whiletheprimaryeffectofPPAR-γactivationistoimproveinsulinsensitivity.Hypothesis:Thehypothesisisthataleglitazarwillreduceadversecardiovascularoutcomes.Drugs/ProceduresUsed:Patientswithtype2diabetesandhospitalizedforanacutecoronarysyndromewererandomizedtoaleglitazar150µg(n=3,616)versusplacebo(n=3,610).ConcomitantMedications:Aspirin(98%),ADPreceptorinhibitor(89%),andstatin(92%)PrincipalFindings:Overall,7,226patientswererandomized.Themeanagewas61years,27%werewomen,meandurationofdiabeteswas8.6years,meanbodymassindexwas29kg/m2,meanglycatedhemoglobinwas7.8%,meanlow-densitylipoproteincholesterol(LDL-C)was79mg/dl,qualifyingeventwasST-segmentelevationmyocardialinfarction(STEMI)in39%,non-STEMIin36%,andunstableanginain25%.Atamedianof104months,thetrialwasterminatedearlyduetofutilityforefficacyandincreasedsafetyendpoints.Atthetimethetrialwasstopped,74%ofpredictedeventshadbeenadjudicated.Comparedwithplacebo,aleglitazarwasassociatedwithimprovementsinglycatedhemoglobin,triglycerides,andhigh-densitylipoproteincholesterol;however,itwasassociatedwithanincreaseinLDL-C.Theprimaryefficacyoutcomeofcardiovasculardeath,MI,orstrokeoccurredin9.5%ofthealeglitazargroupversus10%oftheplacebogroup(p=0.57).-Unstableanginahospitalization:3.3%vs.4.3%(p=0.02),respectively-Unplannedrevascularization:11.0%vs.13.8%(p<0.001),respectively-Hospitalizationforheartfailure:3.4%vs.2.8%(p=0.14),respectively-Gastrointestinal(GI)hemorrhage:2.4%vs.1.7%(p=0.03),respectively-Renaldysfunction:7.4%vs.2.7%(p<0.001),respectively-Bonefracture:2.3%vs.1.8%(p=0.11),respectively-Peripheraledema:14.0%vs.6.6%(p<0.001),respectivelyInterpretation:Amongtype2diabeticpatientshospitalizedforanacutecoronarysyndrome,theuseofthePPAR-αγdual-agonistaleglitazarinadditiontostandardtherapywasnotbeneficial.Aleglitazardidnotreduceadversecardiovascularevents,despitefavorableeffectsonglycatedhemoglobin,HDL-C,andtriglyceridelevels.Infact,aleglitazarwasassociatedwithanexcessofsafetyevents:GIhemorrhage,renaldysfunction,andperipheraledema,andanonsignificantexcessinhospitalizationforheartfailureandbonefracture.Apossibleexplanationforthelackofefficacyincludesthehighprevalenceofstatinsandgoodbaselinelipidcontrol.Also,anincreaseinLDL-CmighthavenegatedbeneficialeffectsfromHDL-Candtriglyceridelowering.Itisunknownifthesameresultswouldhavebeenobservedamongpatientswithnewlydiagnoseddiabetesandlessestablishedatheroscleroticdisease.Thereductionofmacrovasculareventsindiabeticpatientsremainschallenging.来源：CardioSourceNews（March30，2014）【148】AleCardio因安全性及预期疗效被提前终止试验（中文摘要）基于对药品安全性及预期疗效的担忧，早在2013年7月，终止了AleCardio研究，在日前召开的ACC2014年会上揭晓了具体数据。AleCardio研究纳入7226例近期发生急性冠脉综合征的2型糖尿病患者，平均年龄61岁，女性占27%，糖尿病病龄平均8.6年，BMI平均值29kg/m2，平均糖化血红蛋白7.8%，LDL-C平均79mg/dl。在标准内科治疗基础上，随机给予aleglitazar150μg/d（n＝3616）或安慰剂（n＝3610）。中位随访期为104周，由于疗效及安全性问题研究被终止。截至研究被提前终止时，尽管aleglitazar降低了患者的糖化血红蛋白水平并改善了甘油三酯和血清HDL-C水平，但未带来心血管获益，Aleglitazar组9.5%的患者和安慰剂组10%的患者发生了心血管死亡、心肌梗死或卒中（P＝0.57）。胃肠道出血（发生率分别为2.4%vs.1.7%，P＝0.03）和可肾损害（发生率分别为7.4%vs.2.7%，P＜0.001）显著较高。