BloodPressureLoweringTreatmentTrial

BloodPressureLoweringTreatmentTrialists’Collaboration
Abstract ObjectiveTodefinethecardiovasculareffectsofloweringbloodpressure inpeoplewithchronickidneydisease. DesignCollaborativeprospectivemeta-analysisofrandomisedtrials. DatasourcesandeligibilityParticipatingrandomisedtrialsofdrugs tolowerbloodpressurecomparedwithplacebooreachotherorthat comparedifferentbloodpressuretargets,withatleast1000patientyears offollow-upperarm. MainoutcomemeasuresMajorcardiovascularevents(stroke, myocardialinfarction,heartfailure,orcardiovasculardeath)incomposite andindividuallyandallcausedeath. Participants26trials(152290participants),including30295individuals withreducedestimatedglomerularfiltrationrate(eGFR),whichwas definedaseGFR0.60forhomogeneity). ConclusionsBloodpressureloweringisaneffectivestrategyfor preventingcardiovasculareventsamongpeoplewithmoderatelyreduced eGFR.Thereislittleevidencefromtheseoverviewstosupportthe preferentialchoiceofparticulardrugclassesforthepreventionof cardiovasculareventsinchronickidneydisease.
Introduction Chronickidneydisease,mostcommonlydefinedbyareduced glomerularfiltrationrate(GFR)orabnormalconcentrationsof proteinuria,orboth,isanimportantpublichealthproblem, affecting10-15%oftheadultgeneralpopulation.1-3 Itis associatedwithanincreasedriskofkidneyfailureand cardiovasculardisease.4-6Individualswithearlychronickidney diseasearemorelikelytoexperienceacardiovascularevent thankidneyfailure,7andpreciseandreliableevidenceaboutthe effectsofstrategiestopreventcardiovasculardiseaseinthis largepopulationofpatientsisofgreatimportance. Bloodpressureisanimportantdeterminantoftheriskof cardiovasculardiseaseinthegeneralpopulation.8 Itiswell establishedthatinterventionsthatlowerbloodpressureprevent cardiovascularevents.9 10 Bloodpressureiscommonlyraised inindividualswithchronickidneydisease,5 6 andguidelines recommendlowerbloodpressuretargetsinthispopulationthan inpeoplewithoutchronickidneydisease.11 12 Severalstudies havealsosuggestedparticularbenefitsofdrugclassesacting throughtherenin-angiotensinsystemforthepreventionofrenal complications.13 Theevidencethatloweringbloodpressureis beneficialforpatientswithchronickidneydiseaseaswellas thosewithout,however,remainslimited,andthecomparative efficacyofdifferentregimenstolowerbloodpressureonthe riskofcardiovasculareventsinpatientswithandwithoutchronic kidneydiseaseremainsuncertain.14-19 TheBloodPressureLoweringTreatmentTrialists’ Collaboration20 wasestablishedtoperformaseriesof prospectivelydefinedoverviewsofrandomisedtrialsto investigatetheeffectsofbloodpressureloweringdrugson cardiovascularmorbidityandmortality,includingassessments ofthecomparativeeffectsofregimensbetweenmajorpatient subgroups.Thisanalysis,prespecifiedintheoriginal collaborationprotocol,20quantifiestheproportionalbenefitsof bloodpressurelowering,andthecomparativeeffectsofdifferent
Correspondence to:V Perkovic, George Institute for Global Health, University of Sydney, Level 13, 321 Kent St, Sydney NSW 2000, Australia [e-mail]
Extra material supplied by the author (see http://www.bmj.com/content/347/bmj.f5680?tab=related#webextra)
Appendix: Supplementary tables and figures [posted as supplied by author]
No commercial reuse: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ2013;347:f5680doi:10.1136/bmj.f5680(Published3October2013) Page1of15
Research
RESEARCH
classesofbloodpressureloweringdrugsinindividualswith andwithoutchronickidneydisease. Methods Datasourcesandstudyselection Trialswereeligibleforinclusioninthisprospectivecollaborative meta-analysisiftheymetoneofthefollowingcriteria:patients wererandomisedtoabloodpressureloweringdrug/regimenor acontrolgroup(placeboorlessintensivebloodpressure loweringregimen)orpatientswererandomisedbetween regimensbasedondifferentclassesofdrugstolowerblood pressure.Trialswerealsorequiredtohaveaminimumof1000 patientyearsofplannedfollow-upineachrandomisedarmand nottohavepresentedorpublishedtheirmainresultsbefore finalisationoftheoverviewprotocolinJuly1995.20 The collaborationwasjointlyestablishedbytheprincipal investigatorsin1995,andtheinclusioncriteriaforthe overviews20 specifiedthatresultsoftrialsreportedonlyafter thistimecouldbeincluded.Intheearlyyearsofthe collaboration,participantscontributedaggregatetrialdatabut, overtime,agreedtoprovideindividualpatientdata.Newtrials wereidentifiedbyarangeofmethodsincludingcomputeraided literaturesearches,scrutinyofabstractsandproceedingsof meeting,andbyinquiringamongcolleagues,collaborators,and themanufacturersofantihypertensivedrugs.Determinationof eligibilitywasbasedonareviewofdetailsofthestudydesign andqualityofthestudy,regardlessofmainresultsofeachtrial (appendixtable1).Theprincipalinvestigatorsforeligibletrials wereinvitedtojointhecollaborationastheywereidentified. Trialsforwhichdatabykidneyfunctionhadbeenobtainedby April2012wereincludedintheseanalyses.Forthisoverview, datawereavailablefrom26trialsprovidingeitherindividual participantdataincludingserumcreatinineconcentrations(23 trials21-44)orsummarydatastratifiedbyestimatedglomerular filtrationrate(tabulardatafromtwotrials15 45 andpublished hazardratiosfromonetrial14).Amongthem,25trials14 15 21-44 wereincludedinthemainanalyses,whileonetrial45contributed participantsonlytothereducedeGFRstratumandwasincluded insensitivityanalyses.Dataregardingurinaryproteinexcretion atbaselinewereavailablefor11trials.21 22 24 27-32 37 40 Two trials15 34 39didnotprovideinformationregardingthecombined endpointofmajorcardiovasculareventsaccordingtochronic kidneydiseasestatusbutprovideddataforotherendpoints.The individualparticipantdatarequestedincludedcharacteristicsof participantsrecordedatscreeningorrandomisation,selected measurementsduringfollow-up,anddetailsofalloutcomes duringthescheduledfollow-upperiod.WeusedtheCochrane Collaboration’stooltoassesstheriskofbias.46 Glomerularfiltrationratesandproteinuria Glomerularfiltrationrateswereestimatedwiththemodification ofdietinrenaldiseaseformula7: eGFR=186.3×(serumcreatinine/88.4)−1.154×(age)−0.203×1.210(if black)×0.742(iffemale) whereeGFRisinmL/min/1.73m2,ageisinyears,andserum creatinineisinµmol/L.Theparticipantsweredividedintotwo categoriesofbaselineeGFR(≥60mL/min/1.73m2 orand300mg/day, urinaryalbuminconcentration>200mg/L,urinaryalbumin creatinineratio>300μg/mg,oraurinaryproteindipsticktest resultof1+orgreater.7 Stagesofchronickidneydiseasewere definedaccordingtotheguidelinesfromtheKidneyDisease OutcomesQualityInitiative(K/DOQI).11 Outcomes Thesixoutcomesweredefinedaccordingtotheinternational classificationofdiseasesandwereprespecifiedinthe collaboration’sprotocol.20 Outcomeswerestroke(non-fatal strokeordeathfromcerebrovasculardisease),coronaryheart disease(non-fatalmyocardialinfarctionordeathfromcoronary heartdiseaseincludingsuddendeath),heartfailure(causing deathorrequiringadmissiontohospital),cardiovasculardeath, andtotalmortality.Themainoutcomewasmajorcardiovascular eventscomprisingstroke,coronaryheartdisease,heartfailure, andcardiovasculardeath.Onlythefirsteventoftherelevant outcometypewasincludedineachanalysis. Treatmentcomparisons Thetreatmentcomparisonstestedwereprespecifiedinthe originalprotocol.20 Inthebroadgroupoftrialscomparingan activetreatmentandacontrol,wecarriedoutseparateoverviews forangiotensinconvertingenzyme(ACE)inhibitorbased regimensversusplacebo;calciumantagonistbasedregimens versusplacebo;andmoreintensiveversuslessintensiveblood pressureloweringregimens.Inthebroadgroupoftrials comparingdifferentactiveagents,wecarriedoutseparate overviewsforACEinhibitorbasedregimensversusconventional treatment(diureticsorβblockerbasedregimens);calcium antagonistbasedregimensversusconventionaltreatment;and ACEinhibitorbasedregimensversuscalciumantagonistbased regimens. Datasynthesisandanalysis Bloodpressurereductions Thereductioninbloodpressureineachtrialarmwascalculated asthemeanofthedifferencebetweeneachparticipant’smean bloodpressureduringfollow-upandtheirbloodpressureat baseline.Themeandifferenceinbloodpressurebetween randomisedgroupswasthencalculatedbysubtractingthevalues forthetwoarmsaccordingtochronickidneydiseasestatus. Meta-analysesofsubgroupsaccordingtokidney function. Toinvestigatetheeffectsofactivetreatmentcomparedwith placebo,moreintensivecomparedwithlessintensiveregimens, ordifferentdrugclassesontheoutcomesinpatientswith differentbaselineeGFR,weperformedmeta-analysesaccording tokidneyfunction.Allthemeta-analysesusedatwostage approachwherebytheriskestimateswerefirstsummarisedin eachtrialandthencombined. Foreachtrialandeachoutcome,weestimatedtheriskestimates separatelyforeachsubgroup,accordingtotheintentiontotreat principle.WecomputedhazardratiosoroddsratiosusingaCox proportionalhazar

ผลลัพธ์ (ไทย) 1:

ความร่วมมือของ BloodPressureLoweringTreatmentTrialists
inpeoplewithchronickidneydisease ObjectiveTodefinethecardiovasculareffectsofloweringbloodpressure นามธรรม DesignCollaborativeprospectivemeta-analysisofrandomisedtrials DatasourcesandeligibilityParticipatingrandomisedtrialsofdrugs tolowerbloodpressurecomparedwithplacebooreachotherorthat comparedifferentbloodpressuretargetswithatleast1000patientyears offollow-upperarm MainoutcomemeasuresMajorcardiovascularevents (จังหวะ myocardialinfarction, heartfailure, orcardiovasculardeath) incomposite andindividuallyandallcausedeath Participants26trials (152290participants), including30295individuals withreducedestimatedglomerularfiltrationrate (eGFR), whichwas definedaseGFR<60mL/min/1.73m2 DataextractionIndividualparticipantdatawereavailablefor23trials, withsummarydatafromanotherthreeMeta-analysisaccordingto baselinekidneyfunctionwasperformedPooledhazardratiosper5mm Hglowerbloodpressurewereestimatedwitharandomeffectsmodel ResultsComparedwithplacebobloodpressureloweringregimens reducedtheriskofmajorcardiovasculareventsbyaboutasixthper5 mmHgreductioninsystolicbloodpressureinindividualswith (eGFR อันตราย ratio0.83,95%confidenceinterval0.76to0.90)andwithoutreduced (0.83,0.79to0.88) withnoevidenceforanydifferenceineffect (P = 1.00forhomogeneity)Convertingenzymeinhibitors Theresultsweresimilarirrespectiveof whetherbloodpressurewasreducedbyregimensbasedonangiotensin, calciumantagonists, ordiuretics/βblockers Therewasnoevidencethattheeffectsofdifferentdrugclassesonmajor cardiovasculareventsvariedbetweenpatientswithdifferenteGFR (P ทั้งหมด > 0.60forhomogeneity) ConclusionsBloodpressureloweringisaneffectivestrategyfor preventingcardiovasculareventsamongpeoplewithmoderatelyreduced eGFR.Thereislittleevidencefromtheseoverviewstosupportthe preferentialchoiceofparticulardrugclassesforthepreventionof cardiovasculareventsinchronickidneydisease.
แนะนำ Chronickidneydiseaseproteinuria orabnormalconcentrationsof glomerularfiltrationrate (GFR) mostcommonlydefinedbyareduced, orboth, isanimportantpublichealthproblem, affecting10-15%oftheadultgeneralpopulation.1-3 Itis associatedwithanincreasedriskofkidneyfailureand cardiovasculardisease.4 6Individualswithearlychronickidney diseasearemorelikelytoexperienceacardiovascularevent thankidneyfailure7andpreciseandreliableevidenceaboutthe effectsofstrategiestopreventcardiovasculardiseaseinthis largepopulationofpatientsisofgreatimportance Bloodpressureisanimportantdeterminantoftheriskof cardiovasculardiseaseinthegeneralpopulation.8 Itiswell establishedthatinterventionsthatlowerbloodpressureprevent cardiovascularevents.9 10 Bloodpressureiscommonlyraised inindividualswithchronickidneydisease5 6 andguidelines recommendlowerbloodpressuretargetsinthispopulationthan inpeoplewithoutchronickidneydisease.11 12 Severalstudies havealsosuggestedparticularbenefitsofdrugclassesacting throughtherenin angiotensinsystemforthepreventionofrenal complications.13 Theevidencethatloweringbloodpressureis beneficialforpatientswithchronickidneydiseaseaswellas thosewithout อย่างไรก็ตาม remainslimitedandthecomparative efficacyofdifferentregimenstolowerbloodpressureonthe riskofcardiovasculareventsinpatientswithandwithoutchronic kidneydiseaseremainsuncertain.14 19 TheBloodPressureLoweringTreatmentTrialists' Collaboration20 wasestablishedtoperformaseriesof prospectivelydefinedoverviewsofrandomisedtrialsto investigatetheeffectsofbloodpressureloweringdrugson cardiovascularmorbidityandmortalityincludingassessments ofthecomparativeeffectsofregimensbetweenmajorpatient ย่อยThisanalysis, prespecifiedintheoriginal collaborationprotocol, 20quantifiestheproportionalbenefitsof bloodpressurelowering, andthecomparativeeffectsofdifferent
ติดต่อกับ: V Perkovic จอร์จ สถาบัน สุขภาพสากล มหาวิทยาลัยซิดนีย์ ระดับ 13, VPerkovic@george 321 เคนท์เซนต์ Sydney NSW 2000 ออสเตรเลียวัสดุ org.au
Extra ที่จัดทำ โดยผู้เขียน (ดู http://www.bmj.com/content/347/bmj.f5680?tab=related #webextra)
ภาคผนวก: ตารางเสริมและตัวเลข [ลงจัดให้ โดยผู้เขียน]
ไม่นำพาณิชย์: ดูสิทธิ และชื่อ http://www.bmj.com/permissions สมัครสมาชิก: http://www.bmj.com/subscribe
BMJ2013;347:f5680doi:10.1136/bmj.f5680(Published3October2013) Page1of15
วิจัย
วิจัย
classesofbloodpressureloweringdrugsinindividualswith andwithoutchronickidneydisease วิธี Datasourcesandstudyselection Trialswereeligibleforinclusioninthisprospectivecollaborative meta-analysisiftheymetoneofthefollowingcriteria:ผู้ป่วย wererandomisedtoabloodpressureloweringdrug/regimenor acontrolgroup (placeboorlessintensivebloodpressure loweringregimen) orpatientswererandomisedbetween regimensbasedondifferentclassesofdrugstolowerblood ความดันTrialswerealsorequiredtohaveaminimumof1000 patientyearsofplannedfollow upineachrandomisedarmand nottohavepresentedorpublishedtheirmainresultsbefore finalisationoftheoverviewprotocolinJuly1995.20 collaborationwasjointlyestablishedbytheprincipal investigatorsin1995, andtheinclusioncriteriaforthe overviews20 specifiedthatresultsoftrialsreportedonlyafter thistimecouldbeincludedความร่วมมือ Intheearlyyearsofthe, participantscontributedaggregatetrialdatabut ล่วงเวลา agreedtoprovideindividualpatientdataNewtrials wereidentifiedbyarangeofmethodsincludingcomputeraided literaturesearches ประชุม scrutinyofabstractsandproceedingsof, andbyinquiringamongcolleagues ผู้ร่วมงาน และ themanufacturersofantihypertensivedrugsAndqualityofthestudy eligibilitywasbasedonareviewofdetailsofthestudydesign Determinationof, regardlessofmainresultsofeachtrial (appendixtable1)Theprincipalinvestigatorsforeligibletrials wereinvitedtojointhecollaborationastheywereidentified Trialsforwhichdatabykidneyfunctionhadbeenobtainedby April2012wereincludedintheseanalyses.Forthisoverview datawereavailablefrom26trialsprovidingeitherindividual participantdataincludingserumcreatinineconcentrations (23 trials21-44) orsummarydatastratifiedbyestimatedglomerular filtrationrate (tabulardatafromtwotrials15 45 andpublished hazardratiosfromonetrial14)Amongthem, 25trials14 15 21-44 wereincludedinthemainanalyseswhileonetrial45contributed participantsonlytothereducedeGFRstratumandwasincluded insensitivityanalysesDataregardingurinaryproteinexcretion atbaselinewereavailablefor11trials.21 22 24 27-32 37 40 สอง trials15 34 39didnotprovideinformationregardingthecombined endpointofmajorcardiovasculareventsaccordingtochronic kidneydiseasestatusbutprovideddataforotherendpointsIndividualparticipantdatarequestedincludedcharacteristicsof participantsrecordedatscreeningorrandomisation เลือก สาย measurementsduringfollow, anddetailsofalloutcomes duringthescheduledfollow-upperiodWeusedtheCochrane Collaboration'stooltoassesstheriskofbias.46 Glomerularfiltrationratesandproteinuria Glomerularfiltrationrateswereestimatedwiththemodification ofdietinrenaldiseaseformula7: eGFR = 186.3 ×(serumcreatinine/88.4) × −0.203 × (อายุ) −1.154 1.210 (ถ้า black)×0.742(iffemale) whereeGFRisinmL/min/1.73m2,ageisinyears,andserum creatinineisinµmol/L.Theparticipantsweredividedintotwo categoriesofbaselineeGFR (≥60mL/min/1.73m2 orand < 60 mL/min/1.73m2)withestablishedcutpointsrecommendedin renalguidelines11Publisheddatafromtwotrialsinwhichkidney 125-iothalamateclearance45 หรือ functionwasestimatedwiththeCockcroft Gaultformula14 andpatientswerecategorisedas havingeGFR < presenceofproteinuriawasdefinedasanyofthefollowing sufficientlycomparableandincludedinthemainanalysis.The 65mL/minand≥65mL/minweredeemed:
urinaryalbuminexcretionrates > 200μg/วิชา รอง > 300 มิลลิกรัม urinaryalbuminconcentration > 200mg/Lurinaryalbumin creatinineratio > 300μg/มิลลิกรัม, oraurinaryproteindipsticktest resultof1 orgreater.7 Stagesofchronickidneydiseasewere definedaccordingtotheguidelinesfromtheKidneyDisease OutcomesQualityInitiative(K/DOQI) collaboration'sprotocol classificationofdiseasesandwereprespecifiedinthe Thesixoutcomesweredefinedaccordingtotheinternational ผล.1120 Outcomeswerestroke (ไม่ร้ายแรง strokeordeathfromcerebrovasculardisease), โรค coronaryheart (ไม่ใช่ fatalmyocardialinfarctionordeathfromcoronary heartdiseaseincludingsuddendeath), heartfailure (เกิด deathorrequiringadmissiontohospital), cardiovasculardeath, andtotalmortalityThemainoutcomewasmajorcardiovascular eventscomprisingstroke, coronaryheartdisease, heartfailure, andcardiovasculardeathOnlythefirsteventoftherelevant outcometypewasincludedineachanalysis Treatmentcomparisons Thetreatmentcomparisonstestedwereprespecifiedinthe originalprotocol.20 Inthebroadgroupoftrialscomparingan activetreatmentandacontrol, wecarriedoutseparateoverviews forangiotensinconvertingenzyme (เอ) inhibitorbased regimensversusplacebo; calciumantagonistbasedregimens versusplaceboandmoreintensiveversuslessintensiveblood pressureloweringregimensInthebroadgroupoftrials comparingdifferentactiveagents, wecarriedoutseparate overviewsforACEinhibitorbasedregimensversusconventional รักษา (diureticsorβblockerbasedregimens); แคลเซียม antagonistbasedregimensversusconventionaltreatment และ ACEinhibitorbasedregimensversuscalciumantagonistbased regimens Datasynthesisandanalysis Bloodpressurereductions Thereductioninbloodpressureineachtrialarmwascalculated asthemeanofthedifferencebetweeneachparticipant'smean bloodpressureduringfollow upandtheirbloodpressureat พื้นฐานThemeandifferenceinbloodpressurebetween randomisedgroupswasthencalculatedbysubtractingthevalues forthetwoarmsaccordingtochronickidneydiseasestatus Meta-analysesofsubgroupsaccordingtokidney ฟังก์ชัน พลาซีโบ Toinvestigatetheeffectsofactivetreatmentcomparedwith, moreintensivecomparedwithlessintensiveregimens, ordifferentdrugclassesontheoutcomesinpatientswith differentbaselineeGFR, tokidneyfunction weperformedmeta-analysesaccordingAllthemeta analysesusedatwostage approachwherebytheriskestimateswerefirstsummarisedin eachtrialandthencombined Foreachtrialandeachoutcome, weestimatedtheriskestimates separatelyforeachsubgroup, accordingtotheintentiontotreat หลักWecomputedhazardratiosoroddsratiosusingaCox proportionalhazar

ผลลัพธ์ (ไทย) 2:

BloodPressureLoweringTreatmentTrialists’Collaboration
Abstract ObjectiveTodefinethecardiovasculareffectsofloweringbloodpressure inpeoplewithchronickidneydisease. DesignCollaborativeprospectivemeta-analysisofrandomisedtrials. DatasourcesandeligibilityParticipatingrandomisedtrialsofdrugs tolowerbloodpressurecomparedwithplacebooreachotherorthat comparedifferentbloodpressuretargets,withatleast1000patientyears offollow-upperarm. MainoutcomemeasuresMajorcardiovascularevents(stroke, myocardialinfarction,heartfailure,orcardiovasculardeath)incomposite andindividuallyandallcausedeath. Participants26trials(152290participants),including30295individuals withreducedestimatedglomerularfiltrationrate(eGFR),whichwas definedaseGFR<60mL/min/1.73m2. DataextractionIndividualparticipantdatawereavailablefor23trials, withsummarydatafromanotherthree.Meta-analysisaccordingto baselinekidneyfunctionwasperformed.Pooledhazardratiosper5mm Hglowerbloodpressurewereestimatedwitharandomeffectsmodel. ResultsComparedwithplacebo,bloodpressureloweringregimens reducedtheriskofmajorcardiovasculareventsbyaboutasixthper5 mmHgreductioninsystolicbloodpressureinindividualswith(hazard ratio0.83,95%confidenceinterval0.76to0.90)andwithoutreduced eGFR(0.83,0.79to0.88),withnoevidenceforanydifferenceineffect (P=1.00forhomogeneity).Theresultsweresimilarirrespectiveof whetherbloodpressurewasreducedbyregimensbasedonangiotensin convertingenzymeinhibitors,calciumantagonists,ordiuretics/βblockers. Therewasnoevidencethattheeffectsofdifferentdrugclassesonmajor cardiovasculareventsvariedbetweenpatientswithdifferenteGFR(all P>0.60forhomogeneity). ConclusionsBloodpressureloweringisaneffectivestrategyfor preventingcardiovasculareventsamongpeoplewithmoderatelyreduced eGFR.Thereislittleevidencefromtheseoverviewstosupportthe preferentialchoiceofparticulardrugclassesforthepreventionof cardiovasculareventsinchronickidneydisease.
Introduction Chronickidneydisease,mostcommonlydefinedbyareduced glomerularfiltrationrate(GFR)orabnormalconcentrationsof proteinuria,orboth,isanimportantpublichealthproblem, affecting10-15%oftheadultgeneralpopulation.1-3 Itis associatedwithanincreasedriskofkidneyfailureand cardiovasculardisease.4-6Individualswithearlychronickidney diseasearemorelikelytoexperienceacardiovascularevent thankidneyfailure,7andpreciseandreliableevidenceaboutthe effectsofstrategiestopreventcardiovasculardiseaseinthis largepopulationofpatientsisofgreatimportance. Bloodpressureisanimportantdeterminantoftheriskof cardiovasculardiseaseinthegeneralpopulation.8 Itiswell establishedthatinterventionsthatlowerbloodpressureprevent cardiovascularevents.9 10 Bloodpressureiscommonlyraised inindividualswithchronickidneydisease,5 6 andguidelines recommendlowerbloodpressuretargetsinthispopulationthan inpeoplewithoutchronickidneydisease.11 12 Severalstudies havealsosuggestedparticularbenefitsofdrugclassesacting throughtherenin-angiotensinsystemforthepreventionofrenal complications.13 Theevidencethatloweringbloodpressureis beneficialforpatientswithchronickidneydiseaseaswellas thosewithout,however,remainslimited,andthecomparative efficacyofdifferentregimenstolowerbloodpressureonthe riskofcardiovasculareventsinpatientswithandwithoutchronic kidneydiseaseremainsuncertain.14-19 TheBloodPressureLoweringTreatmentTrialists’ Collaboration20 wasestablishedtoperformaseriesof prospectivelydefinedoverviewsofrandomisedtrialsto investigatetheeffectsofbloodpressureloweringdrugson cardiovascularmorbidityandmortality,includingassessments ofthecomparativeeffectsofregimensbetweenmajorpatient subgroups.Thisanalysis,prespecifiedintheoriginal collaborationprotocol,20quantifiestheproportionalbenefitsof bloodpressurelowering,andthecomparativeeffectsofdifferent
Correspondence to:V Perkovic, George Institute for Global Health, University of Sydney, Level 13, 321 Kent St, Sydney NSW 2000, Australia [e-mail]
Extra material supplied by the author (see http://www.bmj.com/content/347/bmj.f5680?tab=related#webextra)
Appendix: Supplementary tables and figures [posted as supplied by author]
No commercial reuse: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ2013;347:f5680doi:10.1136/bmj.f5680(Published3October2013) Page1of15
Research
RESEARCH
classesofbloodpressureloweringdrugsinindividualswith andwithoutchronickidneydisease. Methods Datasourcesandstudyselection Trialswereeligibleforinclusioninthisprospectivecollaborative meta-analysisiftheymetoneofthefollowingcriteria:patients wererandomisedtoabloodpressureloweringdrug/regimenor acontrolgroup(placeboorlessintensivebloodpressure loweringregimen)orpatientswererandomisedbetween regimensbasedondifferentclassesofdrugstolowerblood pressure.Trialswerealsorequiredtohaveaminimumof1000 patientyearsofplannedfollow-upineachrandomisedarmand nottohavepresentedorpublishedtheirmainresultsbefore finalisationoftheoverviewprotocolinJuly1995.20 The collaborationwasjointlyestablishedbytheprincipal investigatorsin1995,andtheinclusioncriteriaforthe overviews20 specifiedthatresultsoftrialsreportedonlyafter thistimecouldbeincluded.Intheearlyyearsofthe collaboration,participantscontributedaggregatetrialdatabut, overtime,agreedtoprovideindividualpatientdata.Newtrials wereidentifiedbyarangeofmethodsincludingcomputeraided literaturesearches,scrutinyofabstractsandproceedingsof meeting,andbyinquiringamongcolleagues,collaborators,and themanufacturersofantihypertensivedrugs.Determinationof eligibilitywasbasedonareviewofdetailsofthestudydesign andqualityofthestudy,regardlessofmainresultsofeachtrial (appendixtable1).Theprincipalinvestigatorsforeligibletrials wereinvitedtojointhecollaborationastheywereidentified. Trialsforwhichdatabykidneyfunctionhadbeenobtainedby April2012wereincludedintheseanalyses.Forthisoverview, datawereavailablefrom26trialsprovidingeitherindividual participantdataincludingserumcreatinineconcentrations(23 trials21-44)orsummarydatastratifiedbyestimatedglomerular filtrationrate(tabulardatafromtwotrials15 45 andpublished hazardratiosfromonetrial14).Amongthem,25trials14 15 21-44 wereincludedinthemainanalyses,whileonetrial45contributed participantsonlytothereducedeGFRstratumandwasincluded insensitivityanalyses.Dataregardingurinaryproteinexcretion atbaselinewereavailablefor11trials.21 22 24 27-32 37 40 Two trials15 34 39didnotprovideinformationregardingthecombined endpointofmajorcardiovasculareventsaccordingtochronic kidneydiseasestatusbutprovideddataforotherendpoints.The individualparticipantdatarequestedincludedcharacteristicsof participantsrecordedatscreeningorrandomisation,selected measurementsduringfollow-up,anddetailsofalloutcomes duringthescheduledfollow-upperiod.WeusedtheCochrane Collaboration’stooltoassesstheriskofbias.46 Glomerularfiltrationratesandproteinuria Glomerularfiltrationrateswereestimatedwiththemodification ofdietinrenaldiseaseformula7: eGFR=186.3×(serumcreatinine/88.4)−1.154×(age)−0.203×1.210(if black)×0.742(iffemale) whereeGFRisinmL/min/1.73m2,ageisinyears,andserum creatinineisinµmol/L.Theparticipantsweredividedintotwo categoriesofbaselineeGFR(≥60mL/min/1.73m2 orand<60 mL/min/1.73m2)withestablishedcutpointsrecommendedin renalguidelines.11Publisheddatafromtwotrialsinwhichkidney functionwasestimatedwiththeCockcroft-Gaultformula14 or 125-iothalamateclearance45 andpatientswerecategorisedas havingeGFR<65mL/minand≥65mL/minweredeemed sufficientlycomparableandincludedinthemainanalysis.The presenceofproteinuriawasdefinedasanyofthefollowing:
urinaryalbuminexcretionrates>200μg/minor>300mg/day, urinaryalbuminconcentration>200mg/L,urinaryalbumin creatinineratio>300μg/mg,oraurinaryproteindipsticktest resultof1+orgreater.7 Stagesofchronickidneydiseasewere definedaccordingtotheguidelinesfromtheKidneyDisease OutcomesQualityInitiative(K/DOQI).11 Outcomes Thesixoutcomesweredefinedaccordingtotheinternational classificationofdiseasesandwereprespecifiedinthe collaboration’sprotocol.20 Outcomeswerestroke(non-fatal strokeordeathfromcerebrovasculardisease),coronaryheart disease(non-fatalmyocardialinfarctionordeathfromcoronary heartdiseaseincludingsuddendeath),heartfailure(causing deathorrequiringadmissiontohospital),cardiovasculardeath, andtotalmortality.Themainoutcomewasmajorcardiovascular eventscomprisingstroke,coronaryheartdisease,heartfailure, andcardiovasculardeath.Onlythefirsteventoftherelevant outcometypewasincludedineachanalysis. Treatmentcomparisons Thetreatmentcomparisonstestedwereprespecifiedinthe originalprotocol.20 Inthebroadgroupoftrialscomparingan activetreatmentandacontrol,wecarriedoutseparateoverviews forangiotensinconvertingenzyme(ACE)inhibitorbased regimensversusplacebo;calciumantagonistbasedregimens versusplacebo;andmoreintensiveversuslessintensiveblood pressureloweringregimens.Inthebroadgroupoftrials comparingdifferentactiveagents,wecarriedoutseparate overviewsforACEinhibitorbasedregimensversusconventional treatment(diureticsorβblockerbasedregimens);calcium antagonistbasedregimensversusconventionaltreatment;and ACEinhibitorbasedregimensversuscalciumantagonistbased regimens. Datasynthesisandanalysis Bloodpressurereductions Thereductioninbloodpressureineachtrialarmwascalculated asthemeanofthedifferencebetweeneachparticipant’smean bloodpressureduringfollow-upandtheirbloodpressureat baseline.Themeandifferenceinbloodpressurebetween randomisedgroupswasthencalculatedbysubtractingthevalues forthetwoarmsaccordingtochronickidneydiseasestatus. Meta-analysesofsubgroupsaccordingtokidney function. Toinvestigatetheeffectsofactivetreatmentcomparedwith placebo,moreintensivecomparedwithlessintensiveregimens, ordifferentdrugclassesontheoutcomesinpatientswith differentbaselineeGFR,weperformedmeta-analysesaccording tokidneyfunction.Allthemeta-analysesusedatwostage approachwherebytheriskestimateswerefirstsummarisedin eachtrialandthencombined. Foreachtrialandeachoutcome,weestimatedtheriskestimates separatelyforeachsubgroup,accordingtotheintentiontotreat principle.WecomputedhazardratiosoroddsratiosusingaCox proportionalhazar

ผลลัพธ์ (ไทย) 3:

bloodpressureloweringtreatmenttrialists'collaboration
นามธรรม objectivetodefinethecardiovasculareffectsofloweringbloodpressure inpeoplewithchronickidneydisease . designcollaborativeprospectivemeta analysisofrandomisedtrials . datasourcesandeligibilityparticipatingrandomisedtrialsofdrugs comparedifferentbloodpressuretargets tolowerbloodpressurecomparedwithplacebooreachotherorthat ,withatleast1000patientyears offollow upperarm . mainoutcomemeasuresmajorcardiovascularevents ( จังหวะ myocardialinfarction ใจวาย , , , orcardiovasculardeath ) incomposite andindividuallyandallcausedeath . participants26trials ( 152290participants ) including30295individuals withreducedestimatedglomerularfiltrationrate ( egfr ) ซึ่ง definedasegfr < 60 ml / min / 1.73m2 .dataextractionindividualparticipantdatawereavailablefor23trials withsummarydatafromanotherthree.meta-analysisaccordingto baselinekidneyfunctionwasperformed.pooledhazardratiosper5mm , hglowerbloodpressurewereestimatedwitharandomeffectsmodel . resultscomparedwithplacebo ,bloodpressureloweringregimens reducedtheriskofmajorcardiovasculareventsbyaboutasixthper5 mmhgreductioninsystolicbloodpressureinindividualswith ( อันตราย ratio0.83,95 % confidenceinterval0.76to0.90 ) andwithoutreduced egfr ( 0.83,0.79to0.88 ) withnoevidenceforanydifferenceineffect ( P = 1.00forhomogeneity )theresultsweresimilarirrespectiveof whetherbloodpressurewasreducedbyregimensbasedonangiotensin convertingenzymeinhibitors calciumantagonists , ordiuretics / บีตา , บล็อค therewasnoevidencethattheeffectsofdifferentdrugclassesonmajor cardiovasculareventsvariedbetweenpatientswithdifferentegfr ( P > 0.60forhomogeneity )conclusionsbloodpressureloweringisaneffectivestrategyfor preventingcardiovasculareventsamongpeoplewithmoderatelyreduced egfr . thereislittleevidencefromtheseoverviewstosupportthe preferentialchoiceofparticulardrugclassesforthepreventionof cardiovasculareventsinchronickidneydisease .
chronickidneydisease เบื้องต้น ,mostcommonlydefinedbyareduced glomerularfiltrationrate ( GFR ) orabnormalconcentrationsof มี orboth isanimportantpublichealthproblem , , , oftheadultgeneralpopulation.1-3 affecting10-15 % ซึ่ง associatedwithanincreasedriskofkidneyfailureand cardiovasculardisease.4-6individualswithearlychronickidney thankidneyfailure diseasearemorelikelytoexperienceacardiovascularevent ,7andpreciseandreliableevidenceaboutthe effectsofstrategiestopreventcardiovasculardiseaseinthis largepopulationofpatientsisofgreatimportance . bloodpressureisanimportantdeterminantoftheriskof cardiovasculardiseaseinthegeneralpopulation 8 itiswell establishedthatinterventionsthatlowerbloodpressureprevent cardiovascularevents 9 10 inindividualswithchronickidneydisease bloodpressureiscommonlyraised ,5 6 แนวทาง recommendlowerbloodpressuretargetsinthispopulationthan inpeoplewithoutchronickidneydisease.11 12 severalstudies havealsosuggestedparticularbenefitsofdrugclassesacting throughtherenin angiotensinsystemforthepreventionofrenal complications.13 theevidencethatloweringbloodpressureis beneficialforpatientswithchronickidneydiseaseaswellas ขุ่น แต่ remainslimited , ,andthecomparative efficacyofdifferentregimenstolowerbloodpressureonthe riskofcardiovasculareventsinpatientswithandwithoutchronic kidneydiseaseremainsuncertain.14-19 thebloodpressureloweringtreatmenttrialists ' collaboration20 wasestablishedtoperformaseriesof prospectivelydefinedoverviewsofrandomisedtrialsto cardiovascularmorbidityandmortality investigatetheeffectsofbloodpressureloweringdrugson ,includingassessments ofthecomparativeeffectsofregimensbetweenmajorpatient กลุ่มย่อย thisanalysis prespecifiedintheoriginal collaborationprotocol 20quantifiestheproportionalbenefitsof bloodpressurelowering , , ,
andthecomparativeeffectsofdifferent ติดต่อ : V perkovic สถาบันด้านสุขภาพที่จอร์จ มหาวิทยาลัยซิดนีย์ ระดับ 13 , 321 Kent St , ซิดนีย์ , NSW , ออสเตรเลีย vperkovic @ จอร์จorg AU
พิเศษวัสดุที่จัดเตรียม โดยผู้เขียน ( ดู http://www.bmj.com/content/347/bmj.f5680 ? แท็บ = ที่เกี่ยวข้อง# webextra )
ภาคผนวก : ตารางเสริมและตัวเลข [ โพสต์เป็นที่จัดโดยผู้เขียน ]
ไม่ใช่เชิงพาณิชย์ใช้ : เห็นสิทธิและพิมพ์ http://www.bmj.com/permissions สมัครสมาชิก : http : / / www.bmj . com / สมัครสมาชิก
bmj2013 ; 347 : f5680doi : 10.1136 / BMJ . f5680 ( published3october2013 ) page1of15


เพื่อการวิจัยclassesofbloodpressureloweringdrugsinindividualswith andwithoutchronickidneydisease . วิธีการ datasourcesandstudyselection trialswereeligibleforinclusioninthisprospectivecollaborative meta analysisiftheymetoneofthefollowingcriteria :ผู้ป่วย wererandomisedtoabloodpressureloweringdrug / regimenor acontrolgroup ( placeboorlessintensivebloodpressure loweringregimen ) orpatientswererandomisedbetween regimensbasedondifferentclassesofdrugstolowerblood ความดันtrialswerealsorequiredtohaveaminimumof1000 patientyearsofplannedfollow upineachrandomisedarmand nottohavepresentedorpublishedtheirmainresultsbefore finalisationoftheoverviewprotocolinjuly1995.20 ที่ investigatorsin1995 collaborationwasjointlyestablishedbytheprincipal andtheinclusioncriteriaforthe overviews20 , specifiedthatresultsoftrialsreportedonlyafter thistimecouldbeincluded .intheearlyyearsofthe ร่วมกัน participantscontributedaggregatetrialdatabut , โอที , agreedtoprovideindividualpatientdata.newtrials wereidentifiedbyarangeofmethodsincludingcomputeraided literaturesearches scrutinyofabstractsandproceedingsof , ประชุม , andbyinquiringamongcolleagues จะจะ และ themanufacturersofantihypertensivedrugs .การหา eligibilitywasbasedonareviewofdetailsofthestudydesign andqualityofthestudy regardlessofmainresultsofeachtrial , ( appendixtable1 ) theprincipalinvestigatorsforeligibletrials wereinvitedtojointhecollaborationastheywereidentified . trialsforwhichdatabykidneyfunctionhadbeenobtainedby forthisoverview april2012wereincludedintheseanalyses , .datawereavailablefrom26trialsprovidingeitherindividual participantdataincludingserumcreatinineconcentrations ( 23 trials21-44 ) orsummarydatastratifiedbyestimatedglomerular สำหรับทุกอัตรากรอง ( tabulardatafromtwotrials15 45 andpublished hazardratiosfromonetrial14 ) amongthem 25trials14 21-44 wereincludedinthemainanalyses , 15 ,whileonetrial45contributed participantsonlytothereducedegfrstratumandwasincluded insensitivityanalyses . dataregardingurinaryproteinexcretion atbaselinewereavailablefor11trials.21 22 24 - 37 40 สอง trials15 34 39didnotprovideinformationregardingthecombined endpointofmajorcardiovasculareventsaccordingtochronic kidneydiseasestatusbutprovideddataforotherendpoints .การ individualparticipantdatarequestedincludedcharacteristicsof participantsrecordedatscreeningorrandomisation เลือก measurementsduringfollow ขึ้น anddetailsofalloutcomes duringthescheduledfollow-upperiod.weusedthecochrane collaboration' stooltoassesstheriskofbias.46 glomerularfiltrationratesandproteinuria glomerularfiltrationrateswereestimatedwiththemodification ofdietinrenaldiseaseformula7 :egfr = 186.3 × ( serumcreatinine / 88.4 1.338 ) −−× ( อายุ ) - × 1.210 ( ถ้าดำ ) × 0.742 ( iffemale ) whereegfrisinml / มิน / 1.73m2 ageisinyears , รับประทาน , creatinineisin µ mol / l.theparticipantsweredividedintotwo categoriesofbaselineegfr ( ≥ 60 ml / min / 1.73m2 orand < 60 ml / min / 1.73m2 ) withestablishedcutpointsrecommendedin renalguidelines .11publisheddatafromtwotrialsinwhichkidney functionwasestimatedwiththecockcroft-gaultformula14 หรือ 125-iothalamateclearance45 andpatientswerecategorisedas havingegfr < / minand และ≥และ / minweredeemed sufficientlycomparableandincludedinthemainanalysis . presenceofproteinuriawasdefinedasanyofthefollowing :
urinaryalbuminexcretionrates > 200 μกรัม / ผู้เยาว์ > 300 mg / วัน urinaryalbuminconcentration > 200 มก. / ลิตรurinaryalbumin creatinineratio > 300 μกรัม / มิลลิกรัม oraurinaryproteindipsticktest resultof1 orgreater 7 stagesofchronickidneydiseasewere definedaccordingtotheguidelinesfromthekidneydisease outcomesqualityinitiative ( K / doqi ) 11 ผล thesixoutcomesweredefinedaccordingtotheinternational classificationofdiseasesandwereprespecifiedinthe collaboration'sprotocol .20 outcomeswerestroke ( ไม่ร้ายแรง strokeordeathfromcerebrovasculardisease ) coronaryheart โรค ( ไม่ใช่ fatalmyocardialinfarctionordeathfromcoronary heartdiseaseincludingsuddendeath ) ใจวาย ( ก่อให้เกิด deathorrequiringadmissiontohospital ) cardiovasculardeath andtotalmortality , . themainoutcomewasmajorcardiovascular eventscomprisingstroke coronaryheartdisease andcardiovasculardeath ใจวาย , , , .onlythefirsteventoftherelevant outcometypewasincludedineachanalysis . treatmentcomparisons thetreatmentcomparisonstestedwereprespecifiedinthe originalprotocol.20 inthebroadgroupoftrialscomparingan activetreatmentandacontrol wecarriedoutseparateoverviews , forangiotensinconvertingenzyme ( ACE ) inhibitorbased regimensversusplacebo ; calciumantagonistbasedregimens versusplacebo ;andmoreintensiveversuslessintensiveblood pressureloweringregimens . inthebroadgroupoftrials comparingdifferentactiveagents wecarriedoutseparate overviewsforaceinhibitorbasedregimensversusconventional , รักษา ( diureticsor บีตา blockerbasedregimens ) ; แคลเซียม antagonistbasedregimensversusconventionaltreatment และ aceinhibitorbasedregimensversuscalciumantagonistbased อาการdatasynthesisandanalysis bloodpressurereductions thereductioninbloodpressureineachtrialarmwascalculated asthemeanofthedifferencebetweeneachparticipant'smean bloodpressureduringfollow upandtheirbloodpressureat พื้นฐาน themeandifferenceinbloodpressurebetween randomisedgroupswasthencalculatedbysubtractingthevalues forthetwoarmsaccordingtochronickidneydiseasestatus .เมตา analysesofsubgroupsaccordingtokidney ฟังก์ชัน toinvestigatetheeffectsofactivetreatmentcomparedwith ) moreintensivecomparedwithlessintensiveregimens ordifferentdrugclassesontheoutcomesinpatientswith differentbaselineegfr , , analysesaccording weperformedmeta tokidneyfunction.allthemeta-analysesusedatwostage approachwherebytheriskestimateswerefirstsummarisedin eachtrialandthencombined .foreachtrialandeachoutcome weestimatedtheriskestimates separatelyforeachsubgroup accordingtotheintentiontotreat principle.wecomputedhazardratiosoroddsratiosusingacox proportionalhazar , ,