鈣拮抗劑治療高血壓重要臨床試驗回顧.ppt

鈣拮抗劑治療高血壓重要臨床試驗回顧,高血壓治療研究進程,1960s能否有效降低血壓1970s降壓能否改善患者預后1980s老年人群降壓是否有益1990s各類降壓藥對預后影響有無差異,有關鈣拮抗劑的重要臨床試驗,Syst-EurSyst-ChinaSTONEHOTSTOP-2INSIGHTNORDIL,達到終點的患者比例,0123456隨機后的時間(年),STOP-2研究中各組達到終點的患者比例,危險患者鈣拮抗劑219621562094202919501422376ACEI220521592104204219581405352傳統(tǒng)藥物221321632118205719791426368,SYOPH2，Lancet.1999;354:1751.,INSIGHT試驗,臨床預后：所有終點*的發(fā)生率,*包括所有主要終點以及非心腦血管性死亡、腎衰、心絞痛和短暫性腦缺血,患者百分數(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)表試驗的主要結果,入選的臨床試驗(一),簡稱病例數(shù)對象計劃隨訪(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(二),簡稱病例數(shù)對象計劃隨訪(年)完成ELSA2251HBP42000HDS1148HBP+Diabetes8.21998HOPE9541CVD(risk)4.72000HOT19196HBP3.51997HYVET2100HBP52001INSIGHT6592HBP+CVD(risk)31999LIFE9194HBP+LVH42001NICE-EH1000HBP51997NORDIL11000HBP52002PART2617Atherosclerosis41998PHYLLIS450CIT32000,入選的臨床試驗(三),簡稱病例數(shù)對象計劃隨訪(年)完成PREVENT285ACHD51997PROGRESS6000StrokeorTIA52000QUIET1750ACHD31996RENAAL1500Diabetes42002SCOPE4000HBP2.52003SHELL4800HBP3.51999STOP-26628HBP41998SYST-EUR4695ISH1.61997VHAS1414HBP21996,BPLT協(xié)作研究一級終點,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,降壓藥與安慰劑比較HOPE，PART2，QUIET，SCAT，PREVENT，SYST-EUR不同降壓目標值比較ABCD，HOT，UKPDS-HDS不同降壓藥物比較CAPPP，STOP-2，UKPDS-HDS，INSIGHT，NICE-EH，NORDIL，VHAS，ABCD,相對危險計算,BPLT協(xié)作研究第一輪分析結果(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論,證實ACEIs和長效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減少CVD事件發(fā)生能增加益處相對于降壓治療獲得的益處，不同類型降壓藥為基礎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,入選的臨床試驗數(shù)、病例數(shù)和事件數(shù)尚未達到作出肯定結論的條件，尤其在評價不同類型降壓藥對終點事件影響的差別時不同臨床試驗的樣本量相差很大，其中HOPE、SYST-EUR、HOT、STOP-2等試驗的結果起了決定性影響，而這些臨床試驗的對象和設計是特定的大部分入選的臨床試驗在治療過程中有較高的失隨訪率(30%)，可能對意向治療分析(ITT)的結果造成偏差,ProjectedNumbersofSubjects2000BasedonCurrentCollaboratingStudies,Theroleofbloodpressureitselfbecomespredominantathighbloodpressurelevelsbutislessimportantwhenpressureislowerandnon-pressure-dependentmechanismsbecomeofgreaterimportance.Thecurvesarehypothetical.,降壓治療試驗終點事件比較(/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,社會經(jīng)濟狀況具體患者的心腦血管病危險因素狀況是否有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