西洛他唑的最新研究及存在的问题ppt课件.ppt

西洛他唑的最新研究及存在的问题南京鼓楼医院计成 Newprogression CSPS Combination Announcements AboutCilostazol Cilostazol Pletaal 1988improvementofischemicsymptomsincludingulcers painandcoldnessassociatedwithchronicarterialobstructionastheindicationinJapan InApril2003 secondarypreventionofcerebralinfarction excludingcardiogeniccerebralembolism wasapprovedastheadditionalindication 主要试验 1 CilostazolStrokePreventionStudy aplacebocontrolledtrialdouble blindtrialforsecondarypreventionofcerebralinfarction 2 ARandomizedDouble blindStudyOfCilostazolAndAspirin CilostazolStrokePreventionStudyII CSPSII 3 EffectofCilostazolintheAcuteLacunarInfarctionBasedonPulsatilityIndexofTranscranialDoppler 1 CilostazolStrokePreventionStudy CSPS 试验对象 采用随机 双盲 安慰剂对照的方法 平均随访2年 病例来自日本183个临床研究所 1052例受试者参与试验 西洛他唑组 526例安慰剂组 526例 排除标准 既往有脑出血病史 既往或未来可能有心源性脑栓塞或任何相关的并发症 严重的脑梗死导致日常生活能力丧失 生活不能自理者 痴呆 对西洛他唑有禁忌证者 入选标准 年龄 80岁 在1992年4月 1996年3月患脑梗死的患者 如果该患者在随机入选前1 6个月发生脑梗死也符合入选标准 并无严重的并发症 颈内动脉 基底动脉系统的脑梗死均包括在研究范围中 方法 治疗组接受西洛他唑100mg 2 d口服 对照组采用安慰剂口服 平均随访时间 治疗组651 8d安慰剂组569 7d 主要终点事件 脑梗死复发 其次是心肌梗死 颅内出血 短暂性脑缺血发作 TIA 心绞痛 肺栓塞 静脉血栓形成以及死亡 2组人群的基线特征包括年龄 性别 临床资料 卒中的类型 梗死灶大小 糖尿病 高血压 心脏病等病史 相匹配 结果 关于终点事件 西洛他唑组有30例脑梗死复发 安慰剂组有57例 年发病率2组分别为3 37 和5 78 西洛他唑组与安慰剂组相比脑梗死复发的相对危险度显著降低 41 7 可信区间为9 2 62 5 有显著的统计学意义 P 0 015 GUIDELINESFORMODERATESTROKE GUIDELINESFORSEVERESTROKE 2 CilostazolStrokePreventionStudyII CSPSII Background Theefficacyofaspirinandotherantiplateletsinsecondarypreventionofcerebralinfarctionhasbeendemonstratedinvariousstudiesandmeta analyses mostlyconductedintheUSandEU Alongwithaspirin ticlopidine andclopidgrel cilostazolisrecommendedforsecondarypreventionofnoncardiogeniccerebralinfarctionintheJapaneseGuidelinesfortheManagementofStroke Objective Thisstudywasdesignedtodemonstratecilostazol snon inferioritytoaspirininsecondarypreventionofstrokeinJapanesepatients Design Thisisamulti center randomized double blindstudytoconfirmthesafetyandefficacyofcilostazolinJapanesecerebralinfarctionpatientscomparedwithaspirin cilostazol 100mg twicedaily aspirin 81mg oncedaily Populationstudied Patientswhosufferedcerebralinfarctionwithin26weekspriortoenrollmentandwhosesymptomswerestablethereafterwererandomlyassignedtoreceiveeithercilostazoloraspirin ThestudyperiodisfromDecember2003 December2008 withindividualpatienttreatmentandobservationbeingbetween1and5years OutcomeMeasures Theprimaryendpointisoccurrence stroke cerebralinfarction cerebralhemorrhage orsubarachnoidhemorrhage Thesecondaryendpoints recurrenceofcerebralinfarction occurrenceofischemiccerebraldisorder occurrenceofall causedeath andoccurrenceofcerebralinfarction cerebralhemorrhage subarachnoidhemorrhage transientischemicattack anginapectoris myocardialinfarction cardiacfailure andhemorrhagerequiringhospitalization Intherandomized double blindstudyofnearly2 700patientswithnon cardioembolicischemicstroke thosetreatedwithcilostazolwere25 7 lesslikelytosufferfromastrokethanthosewhoreceivedaspirin Strokesoccurredin82of1 337cilostazol treatedpatientsandin119of1 335aspirin treatedpatients riskratio 1 33 Ahemorrhagicstrokeorhemorrhagethatrequiredhospitalizationoccurredin23patientstakingcilostazoland57ofthosereceivingaspirin asignificantdifference p 0 001 Combination Managementofperipheralarterialdisease PAD requiresstandardatheroscleroticriskmanagementinterventions However PADisoftencomplicatedbywalkingpain intermittentclaudication IC whichrequiressymptom specifictherapiesaswell Thus allPADpatientsareencouragedtotakeantiplateletagentstoreducetheassociatedrisksofmajorcardiovascularevents andthosewithICmayalsorequiretreatmentwithcilostazol Effectonplateletfunctionofcilostazol clopidogrel andaspirin eachaloneorincombination AtherosclerosisSupplements6 2006 13 19 Ascriteriaforinclusioninthetrial 26patients 71 4 males meanage65 9years wereidentifiedwhohadPADwithIC anABI 0 90 andnocontraindicationstothestudydrugs Announcements 解释 AntiplateletAgentsSarpogrelateandCilostazolAffectExperimentally inducedVentricularArrhythmiasandMortality MaleSprague Dawleyrats CardiovascToxicol 2008 8 127 135 pretreatedwitheitherSARorCIL 5mg kg day for2weeks Epigiven4 8 16 32 and64 g kgat10minintervalsoruntildeathoftheanimals Saline treatedanimalsservedascontrols CoronaryOcclusion Results 1outof17SAR pretreatedratshadanepisodeofsinglePVC4outof17CIL pretreatedratshadanaverageof1 25episodesofsinglePVCs Among12controlanimals 2ratsdeveloped1episodeofsinglePVC SARandCILpretreatmentshadnosignificanteffectsonthebaselineECGvariablesincludingQTandQTcintervals Table1ECGvariablesofcontrol SAR treated andCIL treatedanimalsunderbaselineconditions Table2Variablesofearlyventriculararrhythmiasincontrol SAR pretreated andCIL pretreatedanimalsafterinducingcoronaryarteryocclusion Table3Incidenceandonsettimeofventriculararrhythmiasincontrol SAR pretreated andCIL pretreatedanimalsuponadministrationofcumulativedosesofEpi Table4Incidenceandnumberofsingleprematureventricularcontractionsinc