钙拮抗剂治疗高血压重要临床试验回顾.ppt

钙拮抗剂治疗高血压重要临床试验回顾,高血压治疗研究进程,1960s能否有效降低血压1970s降压能否改善患者预后1980s老年人群降压是否有益1990s各类降压药对预后影响有无差异,有关钙拮抗剂的重要临床试验,Syst-EurSyst-ChinaSTONEHOTSTOP-2INSIGHTNORDIL,达到终点的患者比例,0123456随机后的时间(年),STOP-2研究中各组达到终点的患者比例,危险患者钙拮抗剂219621562094202919501422376ACEI220521592104204219581405352传统药物221321632118205719791426368,SYOPH2，Lancet.1999;354:1751.,INSIGHT试验,临床预后：所有终点*的发生率,*包括所有主要终点以及非心脑血管性死亡、肾衰、心绞痛和短暂性脑缺血,患者百分数%,P=0.62,12.1,12.5,硝苯地平控释片利尿剂联合用药,NORDIL(theNordicDiltiazemStudy),地尔硫卓、利尿剂和B-阻滞剂组均可显著降低血压(分别降低20.3/18.7mmHg，23.3/18.7mmHg，收缩压差异P1000病人年1995年7月前尚未发表试验的主要结果,入选的临床试验(一),简称病例数对象计划随访(年)完成AASK1200HBP+Renal(disease)52001ABCD950Diabetes51998ALLHAT40000HBP+CVD(risk)62002ANBP26000HBP52002ASCOT18000HBP+CVD(risk)52003BENEDICT2400Diabetes32001CAPPP10800HBP51998CONVINCE15000HBP+CVD(risk)52001CSGTEI1650Diabetes+proteinuria32000DIAB-HYCAR4000Diabetes+proteinuria31999,入选的临床试验(二),简称病例数对象计划随访(年)完成ELSA2251HBP42000HDS1148HBP+Diabetes8.21998HOPE9541CVD(risk)4.72000HOT19196HBP3.51997HYVET2100HBP52001INSIGHT6592HBP+CVD(risk)31999LIFE9194HBP+LVH42001NICE-EH1000HBP51997NORDIL11000HBP52002PART2617Atherosclerosis41998PHYLLIS450CIT32000,入选的临床试验(三),简称病例数对象计划随访(年)完成PREVENT285ACHD51997PROGRESS6000StrokeorTIA52000QUIET1750ACHD31996RENAAL1500Diabetes42002SCOPE4000HBP2.52003SHELL4800HBP3.51999STOP-26628HBP41998SYST-EUR4695ISH1.61997VHAS1414HBP21996,BPLT协作研究一级终点,总死亡率CVD死亡率CVD事件(脑卒中、CHD事件、心力衰竭和CVD死亡)脑卒中心肌梗死和CHD死亡心力衰竭(死亡或住院),By2003,theavailabledatashouldprovidegoodpowertodetectmodestdifferencesintheincidenceofeachoftheprincipaloutcomesforthemaintreatmentcomparisons.By1999,however,thepowertoassesssuchcause-specifictreatmenteffectsislikelytobesuboptimal,sotheprincipalfocusofanalysesatthattimewillbethecombinedoutcomeoftotalcardiovascularevents.,JHypertens1998;16:127-137,BPLT协作研究第一轮分析入选的临床试验,降压药与安慰剂比较HOPE，PART2，QUIET，SCAT，PREVENT，SYST-EUR不同降压目标值比较ABCD，HOT，UKPDS-HDS不同降压药物比较CAPPP，STOP-2，UKPDS-HDS，INSIGHT，NICE-EH，NORDIL，VHAS，ABCD,相对危险计算,BPLT协作研究第一轮分析结果(一),ACEIsCCBs利尿剂或b阻滞剂总死亡率0.84(0.76-0.94)0.87(0.70-1.09)0.87CVD死亡率0.74(0.64-0.85)0.72(0.52-0.98)0.79CVD事件0.79(0.73-0.86)0.72(0.59-0.87)Stroke0.70(0.57-0.85)0.61(0.44-0.85)0.61CHD0.80(0.72-0.89)0.79(0.59-1.06)0.84CHF0.84(0.68-1.04)0.72(0.48-1.07),与安慰剂作比较(RR),ACEIPlaceboRelativerisk(95%CI)MajorcardiovasculareventsHOPE726/4645919/46520.79(0.72-0.86)PART233/30840/3090.83(0.54-1.28)QUIET49/87855/8720.88(0.61-1.29)SCAT12/22926/2310.47(0.24-0.90)Overall820/60601040/60640.79(0.73-0.86)(phomog=0.81)CardiovasculardeathHOPE282/4645377/46520.75(0.72-0.91)PART28/30818/3090.45(0.20-1.01)QUIET13/87814/8720.92(0.44-1.95)SCAT4/2297/2310.58(0.17-1.94)Overall307/6060416/60640.74(0.7264-0.85)(phomog=0.57)TotalmortalityHOPE482/4645569/46520.85(0.76-0.95)PART216/30825/3090.64(0.35-1.18)QUIET27/87827/8720.99(0.59-1.68)SCAT8/22911/2310.73(0.30-1.79)Overall533/6060632/60640.84(0.76-0.94)(phomog=0.74),ComparisonsofACE-inhibitor-basedtherapywithplacebo,Numberofevents/totalpatients,RelativeriskFavorsFavorsACE-Iplacebo,BPLT:Lancet2000;355:1955,0.51.02.0,CalciumPlaceboRelativeriskantagonistsI(95%CI)MajorcardiovasculareventsPREVENT24/41730/4080.78(0.47-1.32)SYST-EUR142/2398192/22970.71(0.57-0.87)Overall166/2815222/27050.72(0.59-0.87)(phomog=0.73)CardiovasculardeathPREVENT2/4177/4080.28(0.06-1.34)SYST-EUR64/239882/22970.75(0.54-1.03)Overall66/281589/27050.72(0.52-0.98)(phomog=0.23)TotalmortalltyPREVENT6/4178/4080.73(0.26-2.10)SYST-EUR135/2398147/22970.88(0.70-1.10)Overall141/2815155/27050.87(0.70-1.09)(phomog=0.74),Numberofevents/totalpatients,Comparisonsofcalcium-antagonist-basedtherapywithplacebo,BPLT:Lancet2000;355:1955,0.51.02.0,RelativeriskFavorsFavorscaciumplaceboantagonists,BPLT协作研究第一轮分析结果(二),积极降压的RR总死亡率0.97(0.85-1.11)CVD死亡率0.90(0.75-1.09)CVD事件0.85(0.76-0.96)Stroke0.80(0.65-0.98)CHD0.81(0.67-0.98)CHF0.78(0.53-1.15),MoreLessRelativeriskintensiveintensive(95%CI)MajorcardiovasculareventsABCD36/23738/2330.91(0.60-1.37)HOT228/6262486/125280.94(0.80-1.10)UKPDS-HDS141/758105/3900.69(0.55-0.86)Overall405/7257630/131510.85(0.76-0.96)(phomog=0.08)CardiovasculardeathABCD6/23711/2330.54(0.20-1.43)HOT96/6262177/125281.09(0.85-1.39)UKPDS-HDS80/75858/3900.71(0.52-0.97)Overall182/7257246/131510.90(0.75-1.09)(phomog=0.07)TotalmortalltyABCD10/23722/2330.45(0.22-0.92)HOT207/6262382/125281.08(0.92-1.28)UKPDS-HDS134/75883/3900.83(0.65-1.06)Overall351/7257487/131510.97(0.85-1.11)(phomog=0.02),Numberofevents/totalpatients,Comparisonsofmoreintersivebloodpressureloweringstrategieswithlessintensivestrategies,BPLT:Lancet2000;355:1955,0.51.02.0,RelativeriskFavorsFavorsmorelessintensiveintensive,ACEIsCCBsACEIs利尿剂或b阻滞剂利尿剂或b阻滞剂CCBs总死亡率1.03(0.93-1.14)1.01(0.92-1.11)1.03(0.91-1.18)CVD死亡率1.00(0.87-1.15)1.05(0.92-1.20)1.04(0.87-1.24)CVD事件1.00(0.93-1.08)1.02(0.95-1.10)0.92(0.83-1.01)Stroke1.05(0.92-1.19)0.87(0.77-0.98)1.02(0.85-1.21)CHD1.00(0.88-1.14)1.12(1.00-1.26)0.81(0.68-0.97)CHF0.92(0.77-1.09)1.12(0.95-1.33)0.82(0.67-1.00),BPLT协作研究第一轮分析结果(三)不同类型降压药作比较(RR),ACE-IDiuretioorRelativeriskb-blocker(95%CI)MajoroardlovasculareventsSTOP-2531/2205568/22130.94(0.85-1.04)UKPDS-HDS81/40060/3581.21(0.89-1.63)Subtotal612/2605628/25710.96(0.87-1.06)(phomog=0.12)CAPPP406/5492376/54931.08(0.94-1.24)Overall1018/80971004/80641.00(0.93-1.08)(phomog=0.12)CardiovasculardeathSTOP-2226/2205221/22131.03(0.86-1.22)UKPDS-HDS48/40032/3581.34(0.88-2.05)Subtotal274/2605253/25711.07(0.91-1.26)(phomog=0.25)CAPPP76/549295/54931.08(0.59-1.08)Overall350/8097348/80641.00(0.87-1.15)(phomog=0.13)TotalmortalitySTOP-2380/2205369/22131.03(0.91-1.18)UKPDS-HDS75/40059/3581.14(0.83-1.55)Subtotal455/2605428/25711.05(0.93-1.18)(phomog=0.58)CAPPP184/5492190/54930.97(0.79-1.18)Overall639/8097618/80641.03(0.93-1.14)(phomog=0.68),Numberofevents/totalpatients,0.51.02.0,BPLT:Lancet2000;355:1955,ACE-1CaiciumRelativeriskantagonists(95%CI)MajorcardiovasculareventsABCD28/23547/2350.60(0.39-0.92)STOP-2531/2205562/21960.94(0.85-1.04)Overall559/2440619/24310.92(0.83-1.01)(phomog=0.04)CardiovasculardeathABCD6/23511/2350.55(0.21-1.45)STOP-2226/2205212/21961.06(0.89-1.27)Overall232/2440223/24311.04(0.87-1.24)(phomog=0.19)TotalmortalltyABCD14/23518/2350.78(0.40-1.53)STOP-2380/2205362/21961.05(0.92-1.19)Overall394/2440380/24311.03(0.91-1.18)(phomog=0.40),Numberofevents/totalpatients,ComparisonsofACE-inhibitor-basedtherapywithcalcium-antagonist-basedtherapy,BPLT:Lancet2000;355:1955,0.51.02.0,RelativeriskFavorsFavorsACE-1calciumantagonists,BPLT协作研究第一轮分析的结论,证实ACEIs和长效CCBs降压治疗能显著减少CVD事件发生与CVD死亡率积极降压治疗对减少CVD事件发生能增加益处相对于降压治疗获得的益处，不同类型降压药为基础治疗方案之间的差别较小,BPLT协作研究第一轮分析的局限性,入选的临床试验数、病例数和事件数尚未达到作出肯定结论的条件，尤其在评价不同类型降压药对终点事件影响的差别时不同临床试验的样本量相差很大，其中HOPE、SYST-EUR、HOT、STOP-2等试验的结果起了决定性影响，而这些临床试验的对象和设计是特定的大部分入选的临床试验在治疗过程中有较高的失随访率(30%)，可能对意向治疗分析(ITT)的结果造成偏差,ProjectedNumbersofSubjects2000BasedonCurrentCollaboratingStudies,Theroleofbloodpressureitselfbecomespredominantathighbloodpressurelevelsbutislessimportantwhenpressureislowerandnon-pressure-dependentmechanismsbecomeofgreaterimportance.Thecurvesarehypothetical.,降压治疗试验终点事件比较(/1000病人年),汇萃分析HOT1990年1994年脑卒中4.23.24.4心肌梗死3.07.257.8CVD死亡3.85.36.5总死亡8.39.612.3,血压控制目标值,高血压患者140/90mmHg糖尿病患者130/85mmHg,影响降压药物选择的主要因素,社会经济状况具体患者的心脑血管病危险因素状况是否有TOD和ACC是否有限制某类降压药使用的合并症患者的降压疗效与其它药物相互作用临床