心肌梗塞和脑梗塞溶栓治疗的证据比较

心肌梗塞和脑梗塞溶栓治疗的证据比较摘要：关键词：心肌梗塞和脑梗塞是对人们健康危害极大的一种疾病，死亡率高。它们都是由于血管被血栓阻塞引起的心、脑细胞供血不足所致的缺血性坏死。溶栓药物可以通过溶解血栓、恢复血供来减少心、脑细胞的损伤。溶栓治疗在心肌梗塞已经成为经典的治疗方法之一，大量的随机对照试验（randomizedcontroltrial,RCT）已证实，溶栓治疗能够降低死亡率。但心肌梗塞患者是否溶栓治疗是最佳选择？PTCA相对于溶栓治疗优势何在？由于相同的病理生理机制，脑梗塞患者溶栓治疗情况如何？是最佳选择吗？等等，都是临床医生关心的问题。本文通过复习近年来所发表的，能提供临床证据的RCT和系统评价，对上述问题进行阐述说明。一．检索资源和内容我们检索了最新Cochrane图书馆（2001年第2期）、MEDLINE（1980－2001.6），收集有关心肌梗塞和脑梗塞溶栓治疗的系统评价和Meta分析以及大型的RCT。二．研究结果1．脑梗塞溶栓治疗已完成2个系统评价（systematicreview，SR）。一个SR是评价溶栓治疗对脑梗塞的有效性和安全性，共纳入17个RCT，5216名患者，以死亡率、致残率为试验终点，15个RCT为双盲设计，溶栓药物包括尿激酶、链激酶、重组组织纤维蛋白溶酶原激活物（recombinanttissueplasminogenactivator，tPA）或重组尿激酶原（recombinantpro-urokinase），2个试验采取动脉内给药，余均是静脉途径用药。一半的试验资料是静脉用tPA。trialstestingintravenoustissuePlasminogenActivator.Thrombolytictherapysignificantlyincreasedtheoddsofdeathwithinthefirsttendays(oddsratio[OR]1.85,95%confidenceinterval[CI]1.48to2.32).Themaincauseoftheincreaseindeathswasfatalintracranialhaemorrhagefollowingthrombolysis(OR4.15,95%CI2.96to5.84).Symptomaticintracranialhaemorrhageisalsoincreasedfollowingthrombolysis(OR3.53,95%CI2.79to4.45).Thrombolytictherapyalsoincreasedtheoddsofdeathattheendoffollow-up(OR1.31,95%CI1.13to1.52).Despitethis,thrombolytictherapy,administereduptosixhoursafterischaemicstroke,significantlyreducedtheproportionofpatientswhoweredeadordependent(modifiedRankin3to6)attheendoffollow-up(OR0.83,95%CI0.73to0.94).Forpatientstreatedwithinthreehoursofstroke,thrombolytictherapyappearedmoreeffectiveinreducingdeathordependency(OR0.58,95%CI0.46to0.74)withlessadverseeffectondeath(OR1.11,95%CI0.84to1.47).Therewasheterogeneitybetweenthetrialsthatcouldhavebeendueto:thrombolyticdrugused,variationintheconcomitantuseofaspirinandheparin,severityofthestroke,andtimetotreatment.TrialstestingintravenousrecombinanttissuePlasminogenActivatorsuggestthatitmaybeassociatedwithslightlylesshazardandmorebenefitwhengivenuptosixhoursafterstroke-deathwithinthefirsttendaysOR1.24,95%CI0.85to1.81,deathattheendoffollow-upOR1.16,95%CI0.94to1.44,deadordependentattheendoffollow-upOR0.79,95%CI0.68to0.92.Onetrialthattestedthrombolysisplusaspirinshowedanincreaseindeathsofpatientsgivenbothdrugsincombinationcomparedwiththrombolysisalone.Reviewers'conclusions:Thrombolytictherapyincreasesdeathswithinthefirstseventotendays,anddeathsatfinalfollow-up.Thrombolytictherapyalsosignificantlyincreasessymptomaticandfatalintracranialhaemorrhage.Theserisksareoffsetbyareductionindisabilityinsurvivors,sothatthereis,overall,asignificantnetreductionintheproportionofpatientsdeadordependentinactivitiesofdailyliving.ThedatafromtrialsusingintravenousrecombinanttissuePlasminogenActivator,fromwhichthereisthemostevidenceonthrombolytictherapysofar,suggestthatitmaybeassociatedwithlesshazardandmorebenefit.Therewasheterogeneitybetweenthetrialsandtheoptimumcriteriatoidentifythepatientsmostlikelytobenefitandleastlikelytobeharmed,theagent,dose,androuteofadministration,arenotclear.ThedataarepromisingandmayjustifytheuseofthrombolytictherapywithintravenousrecombinanttissuePlasminogenActivatorinexperiencedcentresinselectedpatients.However,thewidespreaduseofthrombolytictherapyinroutineclinicalpracticeatthistimecannotbesupported.Furthertrialswillbeneededtoidentifywhichpatientsaremostlikelytobenefitfromtreatmentandtheenvironmentinwhichitmaybestbegiven,beforethrombolytictherapyshouldbeadoptedonawiderscale.结果显示，溶栓治疗可以降低随访终点时的死亡率和残废率（OR=0.83，95%CI0.73-0.94），相当于每治疗1000人可以减少44人的死亡或残废。r-tPA在6个试验共有2764人使用，结果显示r-tPA效果更好，（OR=0.79，95%CI0.68-0.92），相当于每治疗1000人减少57人的死亡或残废。1.1短期的死亡率（10天内）溶栓治疗增加短期的死亡率（OR=1.85，95%CI1.48-2.32），等于说每治疗1000人增加了68人的短期死亡；1.2随访终点的死亡率溶栓治疗增加了随访终点时的死亡率（OR=1.31，95%CI1.13-1.52），等于每治疗1000人引起随访终点时的死亡增加了36人；如果使用r-tPA，死亡率增加不明显（OR=1.16，95%CI0.94-1.44），相当于每治疗1000人随访终点时的死亡增加了18人。1.3致死性的颅内出血致死性的颅内出血是引起死亡的主要原因，溶栓组中致死性颅内出血的发生率比对照组几乎高出5倍（OR=4.15，95%CI2.96-5.84）；使用r-tPA比使用链激酶引起颅内出血的发生率低：每治疗1000人，r-tPA增加了29例致死性颅内出血（OR=3.2，95%CI2.0-5.2）而链激酶则增加92例致死性颅内出血（OR=6.03，95%CI3.47-10.47）。1.4非致死性但有临床症状的颅内出血溶栓治疗会明显增加非致死性但有临床症状的颅内出血（OR=3.5，95%CI2.8-4.5），相当于每治疗1000人增加了70人颅内出血。另一SR是评价不同溶栓制剂、给药途径和剂量对脑梗塞的效果。纳入8个RCT，1334个病人，分配方案进行了隐藏，所有试验均在日本进行，adequate.AllthetrialswereconductedinJapan.Differentdoses(oftissueplasminogenactivatororurokinase)werecomparedinseventrials.Differentagents(tissueplasminogenactivatorversusurokinase,ortissue-culturedurokinaseversusconventionalurokinase)werecomparedinthreetrials.Fewdatawereavailableforfunctionaloutcomes.Ahigherdoseofthrombolytictherapywasassociatedwithafive-foldincreaseinfatalintracranialhaemorrhages(oddsratio5.02,95%confidenceinterval1.56to16.18).Thiswasbasedon11eventsamong369higher-dosepatientsandoneeventamong356lower-dosepatientsinsixtrials.Therewasanon-significanttrendtowardsmoreearlydeathsorclinicallysignificantintracranialhaemorrhages.Nodifferenceinlatedeathsorextra-cranialhaemorrhageswasshownbetweenlowandhigherdoses.However,veryfewoftheseeventsoccurred.Nodifferencewasshownbetweenthedifferentthrombolyticagentstested.Reviewers'conclusions:Thereisnotenoughevidencetoconcludewhetherlowerdosesofthrombolyticagentsmightbesaferormoreeffectivethanhigherdoses