降压治疗策略的核心.ppt

降压治疗策略的核心血压控制达标和联合治疗张维忠 0 5 1 0 2 0 RelativeRisk RR 95 CI BPDifference mmHg FavorsFirstListed FavorsSecondListed MajorCVevents CVmortality Totalmortality 1 02 0 98 1 07 2 0 ACEIvsD BB 1 03 0 95 1 11 2 0 ACEIvsD BB 1 00 0 95 1 05 2 0 ACEIvsD BB 1 04 0 99 1 08 1 0 CAvsD BB 1 05 0 97 1 13 1 0 CAvsD BB 0 99 0 95 1 04 1 0 CAvsD BB 0 97 0 92 1 03 1 1 ACEIvsCA 1 03 0 94 1 13 1 1 ACEIvsCA 1 04 0 98 1 10 1 1 ACEIvsCA BloodPressureLoweringTreatmentTrialists Collaboration Lancet 2003 362 1527 1535 BP LoweringTreatmentTrialistsComparisonsofDifferentActiveTreatments INVEST primaryendpoint MIandstrokefreesurvival PepineetalJAMA2003 290 2805 2816 logrankp 0 62 1009590858075 0612182430364248546066 CCBbasedregimenverapamilSR240mgodBetablockerbasedregimenatenolol50mg Cumulativeendpoint Months 22576hypertensiveCADpatients 24months openlabel INVEST血压控制达标与终点事件发生的关系 15 0 5 7 2 4 10 8 4 3 2 3 9 2 3 8 1 6 8 1 3 1 1 1 1614121086420 25 25 至 50 50 至 75 75 随诊时血压达标百分比 140 90mmHg 患者总数 n 3838375766648316 一级终点心肌梗死 致死 非致死性 脑卒中 致死 非致死性 发生临床终点事件百分比 P值均小于0 001 Fatal Non fatalcardiacevents Fatal Non fatalstroke All causedeath Myocardialinfarction Heartfailurehospitalisations 0 4 0 6 0 8 1 0 1 2 1 4 Controlledpatients n 10755 Non controlledpatients n 4490 HazardRatio95 CI SBP 140mmHgat6months PooledTreatmentGroups P 0 01 0 75 0 67 0 83 0 55 0 46 0 64 0 79 0 71 0 88 0 86 0 73 1 01 0 64 0 55 0 74 OddsRatio WeberMAetal Lancet 2004 363 2047 49 VALUE 根据6个月时血压控制情况的结果分析 Fatal Non fatalcardiacevents Fatal Non fatalstroke All causedeath Myocardialinfarction Heartfailurehospitalisations SBP 140mmHgat6months P 0 01 PatientsTreatedWithValsartan PatientsTreatedWithAmlodipine HazardRatio95 CI 0 4 0 6 0 8 1 0 1 2 Controlledpatients n 5253 Non controlledpatients n 2396 0 4 0 6 0 8 1 0 1 2 Controlledpatients n 5502 Non controlledpatients n 2094 HazardRatio95 CI 0 76 0 66 0 88 0 60 0 48 0 74 0 79 0 69 0 91 0 83 0 66 1 03 0 62 0 50 0 77 OddsRatio 0 73 0 63 0 85 0 50 0 39 0 64 0 79 0 69 0 92 0 91 0 71 1 17 0 64 0 52 0 79 OddsRatio WeberMAetal Lancet 2004 363 2047 49 VALUE 根据6个月时血压控制情况的结果分析 Majorcardiovascularevents per100patients years inalltreatedhypertensiveandinhypertensivepatientswithdiabetesinrelationtotargetbloodpressuresof90 85 and80mmHg HOT 糖尿病与非糖尿病患者的CV事件发生率 INVEST糖尿病患者血压控制达标与终点事件发生的关系 MAP meanarterialpressure Bakrisetal AmJKidneyDis 2000 36 646 661 GFR mL min y 14 12 10 8 6 4 2 0 95 98 101 104 107 110 113 116 119 MAP mmHg r 0 69 P 05 Untreatedhypertension 140 90 130 85 9ClinicalTrialsofDiabeticandNondiabeticNephropathy RelationshipBetweenAchievedBPandGFRDecline 收缩压下降差异与终末期肾功能衰竭 ACEIorARB肾病降压临床试验荟萃分析 SBP下降差异ACEI ARB其它干预RR 95 CI n N 对照组 n N 6 9mmHg117 1346155 12910 74 0 59 0 92 9 1to 4 8 1 6mmHg273 6344356 63270 77 0 67 0 89 2 8to 0 4 1 5mmHg206 11049397 260430 90 0 72 1 12 0 1 0 2 CasasJP Lancet2005 366 2026 2033 IDNT 治疗后收缩压水平与肾脏终点事件 SBP mmHg No ofpatients3793574284261590No ofevents 1722 729 238 527irbesartanvs amlodipine placebo12vs2021vs2423vs3231vs4221vs30RRirbesartanvs 0 550 920 660 700 67amlodipine placebo p 0 034 p 0 05 p 0 05 p 0 05 p 0 0002 PohlMA etal JAmSocNephrol2005 16 3027 3037 149Total PohlMC etal JAmSocNephrol2005 16 3027 3037 IDNT ImpactofBPControlandAT1BlockadeonRenalOutcomes RENAAL EffectofBPControl ARBonGFRDecline GFR glomerularfiltrationrate Bakrisetal AmJKidneyDis 2000 36 646 661 Brenneretal NEnglJMed 2001 345 861 869 RateofDeclineinGFR mL min y P 01 NaturalHistory Placebo Losartan 56 withBPcontrol 6 morewithlosartan Benetosetal JHypertens 2003 21 1635 1640 Follow up Years Survival 1 0 96 0 92 0 88 0 84 0 8 1 3 5 7 9 11 13 15 17 19 21 23 25 P 03 P 0001 P 001 CVDSurvivalinTreatedHypertensivesatGoalandNotatGoal 如何使血压控制达标 通常需要2种或2种以上不同降压机制的药物联合治疗 联合治疗时 噻嗪类利尿剂能明显改善血压控制达标率 不同的降压药物和联合治疗方案对长期血压控制存在差异 固定剂量联合制剂提高长期治疗依从性和持续性 有利于血压控制达标 降压治疗方案 序贯治疗 SequentialMonotherapy 阶梯治疗 Stepped care 联合治疗 Combination Percentageofpatientshavingtheirbloodpressure BP normalized 140 90mmHg atthelastvisittrial b PercentageofpatientswhonormalizedtheirBPwithdevelopinganyadverseevent AE MouradJ etal JHypertens 2004 22 2379 2386 INVEST 临床意义 采用积极的治疗策略 联合多种降压药物进行治疗 能够使高血压患者的血压控制在较低水平 平均130 76mmHg 70 患者的血压控制在140 90mmHg以下 要达到上述目标 82 患者需要2种以上药物 51 患者需要3种以上药物 合理的降压联合治疗方案 InitialCombinationsofMedicationsforManagementofHypertension Diuretics ACEinhibitorsorARBs Calciumantagonists Compellingindicationsmaymodifythis 噻嗪类利尿剂治疗高血压的机制 缩减容量减低血管收缩反应性下调AT1受体血管平滑肌细胞钾通道部分开放 噻嗪类利尿剂降压机制血管平滑肌细胞钾通道部分开放 抑制碳酸酐酶 carbonicanhydrase pHi Kca通道激活 开放 SMC超极化 电压依赖性钙通道 PickkersP etal Hypertension 1999 33 1034 1048 ReductioninBPWithCombinationTherapy BP mmHg WeirMRetal AmJHypertens 2001 14 665 671 BNZ 160mgValsartan n 23 HCTZ 160mgValsartan n 30 320mgValsartan n 28 ARBs降压疗效的荟萃分析43项研究 11281例 DBP mmHg 降压有效率 单药低剂量8 2 8 950 单药高剂量9 5 10 455 低剂量 HCTZ9 9 13 670 ConlinPR etal AmJHypertens 2000 13 418 ARBs降压疗效的荟萃分析43项研究 11281例 SBP mmHg DBP mmHg Losartan8 05 5Valsartan7 54 0Irbesartan10 06 5Telmisartan9 56 0Candesartan10 06 0 ConlinPR etal JClinHypertens 2000 2 253 257 BPReductionsObservedinMonotherapywithIrbesartan150mgandValsartan80mg BP Baseline mmHg irbesartan150mg valsartan80mg SelfMeasurement Morningvalues ABPM Trough OfficeMeasurement Trough ADBP ASBP P 0 01 P 0 01 P 0 01 P 0 01 12 8 4 0 P 0 035 P 0 01 DBP SBP SBP DBP 16 12 8 4 0 ManciaGetal BloodPressMonit 2002 7 1 8 8weekstudy 2 5 66 3 2 46 3 2 44 6 2 62 10 5 16 2 7 3 10 0 6 3 10 2 3 8 7 0 4 8 7 5 6 7 11 6 1 9 40 4 1 55 ComparativeStudyofEfficacyofIrbesartan HCTZwithValsartan HCTZUsingHomeBloodPressureMonitoringintheTreAtmentofMild to ModerateHypertension COSIMAStudy COSIMA 研究设计 W0Visit1Enrolmentofhypertensivepatientsuntreatedoruncontrolledbymonotherapy R HCTZ 12 5mgod 5weeks W4Visit2ExclusionifSBP 140mmHg office W13Visit4Finalevaluation 5weeks 8weeks Phase1 Phase2 COSIMA 结果 一 BP final baseline mmHg HBPM averageofallvalues DBP SBP OfficeBP trough DBP SBP P 0 001 P 0 01 2 8 26 16 12 8 4 0 2 2 30 16 12 8 4 0 P 0 05 P 0 01 3 2 28 1 4 21 G Bobrieetal ArchivesMalCoeurVaiss2004 12 p96andp116 9 6 7 4 13 4 10 6 8 2 6 8 14 8 11 6 COSIMA 结果 二 SBP AM PM AM PM DBP BP final baseline mmHg P 0 01 P 0 001 P 0 05 P 0 001 35 12 10 8 6 4 2 0 16 14 20 35 24 3 3 2 4 2 3 2 0 12 7 14 3 9 4 11 9 10 5 8 5 ThePPresultspresentedareconsistentwiththeITTresults8weekstudy G Bobrieetal ArchivesMalCoeurVaiss2004 12 p96andp116 COSIMAMorePatientsNormalisedonIrbesartanCombinationTherapy Patients P 0 0001 Office HBPM P 0 05 NormalHBPMvalues SBP 135mmHgandDBP 85mmHg Normalofficevalues SBP 140mmHgandDBP 90mmHg 19 6 10 3 52 9 33 3 51 5 41 2 ThePPresultsareconsistentwiththeITTresults8weekstudy COSIMA 结论 COSMA研究显示Irbesartan150 HCTZ12 5比Valsartan80 HCTZ12 5能更有效地降低和控制血压 证实不同ARB单药治疗疗效的差异明显影响复合制剂的疗效 AssociationBetweenAdherenceandGoalAttainmentinAntihypertensiveTherapy SturkenboomM etal 15thESHmeeting Milan Italy June17 21 2005 8988例新诊断高血压 平均随访治疗2年 Rotterdam TheNetherlands Persistencewithantihypertensivetreatment 1 0 0 8 0 6 0 4 0 2 0 0 100 200 300 400 500 600 700 800 Daysafterstartofantihypertensivetreatment Proportionofpatientspersistentwithtreatment PatientAdherenceandPersistencewithAntihypertensiveTherapy One versusTwo pillCombination SturkenboomM etal 15thESHmeeting Milan Italy June17 21 2005 ACEI HCTZ n 458 vs ACEI HCTZ n 297 治疗观察2年 比较长期治疗的依从性和持续性 PercentageofpatientsadherenttoA fixed dosecombinationtherapyorB Coadministered0 pilltherapy 100 90 80 70 60 50 40 30 20 10 0 0 3 6 9 12 15 18 21 24 Monthsafterstartoftherapy Percentageofpatients B Adherencetocoadministrationof2pills Non adherent Partiallyadherent Fullyadherent 100 90 80 70 60 50 40 30 20 10 0 0 3 6 9 12 15 18 21 24 Monthsafterstartoftherapy Percentageofpatients A Adherencetofixed dosecombinationtherapy Percentageofpatientsfullyadherenttofixed doseCombinationtherapyandcoadministered2 pilltherapy 100 90 80 70 60 50 40 30 20 10 0 0 3 6 9 12 15 18 21 24 27 Monthsafterstartoftherapy 21 17 Percentageofpatientsfullyadherent Fixed dosecombinationCoadministrationof2pills 安博诺 厄贝沙坦150mg HCTZ12 5mg厄贝沙坦300mg HCTZ12 5mg TheINCLUSIVETrialTheIrbesartan HCTZBloodPressureReductioninDiversePatientPopulation NeutelJM etal JClinHypertens2005 7 578 586 Minimum4weeks 1 005UncontrolledonSingleAntihypertensiveAgent INCLUSIVE StudyDesign Multicenter 119sitesacrosstheUS prospective open label single armstudy Screening INCLUSIVE Demographics 46 n 386 30 n 254 25 n 212 23 n 191 14 n 119 Patients 52 n 436 Week10 Avalide150 12 5mg INCLUSIVE SBP 132 9 13 888 184 21 5 14 3 22 5 20 5 0 001 139 6 12 4108 179 15 1 12 5 16 0 14 1 0 001 154 4 10 2130 179 SBP mmHgMean SDMin maxMeanchange SD95 CIP value Week18 Avalide300 25mg LOCF Baseline 15 1 16 0 14 1 P 0 001 21 5 22 5 20 5 P 0 001 ITTpopulation Week10 Avalide150 12 5mg INCLUSIVE DBP 81 1 9 745 115 10 4 8 7 11 0 9 8 0 001 84 6 8 860 113 7 2 8 0 7 8 6 6 0 001 91 5 8 863 109 DBP mmHgMean SDMin maxMeanchange SD95 CIP value Week18 Avalide300 25mg LOCF Baseline