鈣拮抗劑治療高血壓重要臨床試驗(yàn)回顧.ppt

鈣拮抗劑治療高血壓重要臨床試驗(yàn)回顧,高血壓治療研究進(jìn)程,1960s能否有效降低血壓1970s降壓能否改善患者預(yù)后1980s老年人群降壓是否有益1990s各類降壓藥對(duì)預(yù)后影響有無(wú)差異,有關(guān)鈣拮抗劑的重要臨床試驗(yàn),Syst-EurSyst-ChinaSTONEHOTSTOP-2INSIGHTNORDIL,達(dá)到終點(diǎn)的患者比例,0123456隨機(jī)后的時(shí)間(年),STOP-2研究中各組達(dá)到終點(diǎn)的患者比例,危險(xiǎn)患者鈣拮抗劑219621562094202919501422376ACEI220521592104204219581405352傳統(tǒng)藥物221321632118205719791426368,SYOPH2，Lancet.1999;354:1751.,INSIGHT試驗(yàn),臨床預(yù)后：所有終點(diǎn)*的發(fā)生率,*包括所有主要終點(diǎn)以及非心腦血管性死亡、腎衰、心絞痛和短暫性腦缺血,患者百分?jǐn)?shù)%,P=0.62,12.1,12.5,硝苯地平控釋片利尿劑聯(lián)合用藥,NORDIL(theNordicDiltiazemStudy),地爾硫卓、利尿劑和B-阻滯劑組均可顯著降低血壓(分別降低20.3/18.7mmHg，23.3/18.7mmHg，收縮壓差異P1000病人年1995年7月前尚未發(fā)表試驗(yàn)的主要結(jié)果,入選的臨床試驗(yàn)(一),簡(jiǎn)稱病例數(shù)對(duì)象計(jì)劃隨訪(年)完成AASK1200HBP+Renal(disease)52001ABCD950Diabetes51998ALLHAT40000HBP+CVD(risk)62002ANBP26000HBP52002ASCOT18000HBP+CVD(risk)52003BENEDICT2400Diabetes32001CAPPP10800HBP51998CONVINCE15000HBP+CVD(risk)52001CSGTEI1650Diabetes+proteinuria32000DIAB-HYCAR4000Diabetes+proteinuria31999,入選的臨床試驗(yàn)(二),簡(jiǎn)稱病例數(shù)對(duì)象計(jì)劃隨訪(年)完成ELSA2251HBP42000HDS1148HBP+Diabetes8.21998HOPE9541CVD(risk)4.72000HOT19196HBP3.51997HYVET2100HBP52001INSIGHT6592HBP+CVD(risk)31999LIFE9194HBP+LVH42001NICE-EH1000HBP51997NORDIL11000HBP52002PART2617Atherosclerosis41998PHYLLIS450CIT32000,入選的臨床試驗(yàn)(三),簡(jiǎn)稱病例數(shù)對(duì)象計(jì)劃隨訪(年)完成PREVENT285ACHD51997PROGRESS6000StrokeorTIA52000QUIET1750ACHD31996RENAAL1500Diabetes42002SCOPE4000HBP2.52003SHELL4800HBP3.51999STOP-26628HBP41998SYST-EUR4695ISH1.61997VHAS1414HBP21996,BPLT協(xié)作研究一級(jí)終點(diǎn),總死亡率CVD死亡率CVD事件(腦卒中、CHD事件、心力衰竭和CVD死亡)腦卒中心肌梗死和CHD死亡心力衰竭(死亡或住院),By2003,theavailabledatashouldprovidegoodpowertodetectmodestdifferencesintheincidenceofeachoftheprincipaloutcomesforthemaintreatmentcomparisons.By1999,however,thepowertoassesssuchcause-specifictreatmenteffectsislikelytobesuboptimal,sotheprincipalfocusofanalysesatthattimewillbethecombinedoutcomeoftotalcardiovascularevents.,JHypertens1998;16:127-137,BPLT協(xié)作研究第一輪分析入選的臨床試驗(yàn),降壓藥與安慰劑比較HOPE，PART2，QUIET，SCAT，PREVENT，SYST-EUR不同降壓目標(biāo)值比較ABCD，HOT，UKPDS-HDS不同降壓藥物比較CAPPP，STOP-2，UKPDS-HDS，INSIGHT，NICE-EH，NORDIL，VHAS，ABCD,相對(duì)危險(xiǎn)計(jì)算,BPLT協(xié)作研究第一輪分析結(jié)果(一),ACEIsCCBs利尿劑或b阻滯劑總死亡率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),與安慰劑作比較(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協(xié)作研究第一輪分析結(jié)果(二),積極降壓的RR總死亡率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利尿劑或b阻滯劑利尿劑或b阻滯劑CCBs總死亡率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協(xié)作研究第一輪分析結(jié)果(三)不同類型降壓藥作比較(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協(xié)作研究第一輪分析的結(jié)論,證實(shí)ACEIs和長(zhǎng)效CCBs降壓治療能顯著減少CVD事件發(fā)生與CVD死亡率積極降壓治療對(duì)減少CVD事件發(fā)生能增加益處相對(duì)于降壓治療獲得的益處，不同類型降壓藥為基礎(chǔ)治療方案之間的差別較小,BPLT協(xié)作研究第一輪分析的局限性,入選的臨床試驗(yàn)數(shù)、病例數(shù)和事件數(shù)尚未達(dá)到作出肯定結(jié)論的條件，尤其在評(píng)價(jià)不同類型降壓藥對(duì)終點(diǎn)事件影響的差別時(shí)不同臨床試驗(yàn)的樣本量相差很大，其中HOPE、SYST-EUR、HOT、STOP-2等試驗(yàn)的結(jié)果起了決定性影響，而這些臨床試驗(yàn)的對(duì)象和設(shè)計(jì)是特定的大部分入選的臨床試驗(yàn)在治療過(guò)程中有較高的失隨訪率(30%)，可能對(duì)意向治療分析(ITT)的結(jié)果造成偏差,ProjectedNumbersofSubjects2000BasedonCurrentCollaboratingStudies,Theroleofbloodpressureitselfbecomespredominantathighbloodpressurelevelsbutislessimportantwhenpressureislowerandnon-pressure-dependentmechanismsbecomeofgreaterimportance.Thecurvesarehypothetical.,降壓治療試驗(yàn)終點(diǎn)事件比較(/1000病人年),匯萃分析HOT1990年1994年腦卒中4.23.24.4心肌梗死3.07.257.8CVD死亡3.85.36.5總死亡8.39.612.3,血壓控制目標(biāo)值,高血壓患者140/90mmHg糖尿病患者130/85mmHg,影響降壓藥物選擇的主要因素,社會(huì)經(jīng)濟(jì)狀況具體患者的心腦血管病危險(xiǎn)因素狀況是否有TOD和ACC是否有限制某類降壓藥使用的合并癥患者的降壓療效與其它藥物相互作用臨床