降壓治療與心血管病預防課件

BPreductionandCVprevention

降壓治療與心血管病預防

–關注降壓質(zhì)量，豐富高血壓專業(yè)內(nèi)涵–王繼光上海交通大學醫(yī)學院附屬瑞金醫(yī)院上海市高血壓研究所BPreductionandCVprevention1RelativeriskreductionsbyantihypertensivetreatmentinearlytrialsProgressiontosevereHTCHFStrokeCHDTotalmortalityCVmortality-94％*-53%*-40%*-16%*-13%-21%**P<0.05CollinsR,etal.BrMedBull1994;50:272-298.Relativeriskreductionsbyan2BPLTTC.Lancet2003;362:1527-45.0-5-10-15-20-25-30StrokeCHDCHFTotalmortality-23%-15%-16%-14%－4/3mmHgN＝20888MajorCVevents-15%RelativeriskreductionsbyantihypertensivetreatmentinrecenttrialsBPLTTC.Lancet2003;362:1527-43Do5classesofantihypertensivedrugsdifferinthepreventionofCVcomplications?5大類降壓藥物改善結局的作用有差別嗎?Do5classesofantihypertensi41.PreventionofstrokeCCBsaremoreprotectiveagainststroke.預防卒中:CCBs>利尿劑/阻滯劑>ACEIs

1.Preventionofstroke5CCBsvs.

利尿劑/阻滯劑:致死性與非致死性腦卒中利尿劑/阻滯劑CCBs試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)0CCBs較好123利尿劑/阻滯劑較好MIDAS/NICS/VHASSTOP2/CCBsNORDILINSIGHTALLHAT/AmlodipineELSACCBswithoutCONVINCE p=0.68CONVINCE所有CCBs p=0.3915/1358237/2213196/547174/3164675/1525514/11571211/28618118/82971329/3691519/1353207/2196159/541067/3157377/90489/1177838/22341133/8179971/30520–10.2%(4.8)2p=0.02–7.6%(4.4)2p=0.07StaessenJA,etal.Lancet2001;37:1305-15.StaessenJAetal.JHypertens2003;21:1055-76.CCBsvs.利尿劑/阻滯劑:利尿劑/阻滯劑CCB60ACEIs較好123UKPDSSTOP2/ACEIsCAPPPALLHAT/LisinoprilANBP2所有ACEIs p=0.1617/358237/2213148/5493675/15255107/30391184/2635821/400215/2205189/5492457/9054112/3044994/2019510.2%(4.6)2p=0.03ACEIsvs.

利尿劑/阻滯劑:致死性與非致死性腦卒中利尿劑/阻滯劑試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)CCBs利尿劑/阻滯劑較好StaessenJA,etal.Lancet2001;37:1305-15.StaessenJAetal.JHypertens2003;21:1055-76.0ACEIs較好123UKPDS17/35821/400107降壓治療與心血管病預防課件8

相對危險度(95%CI)賴諾普利較好氨氯地平較好+1%(–9%to+11%)CHD+5%(–3%to+13%)總死亡率+4%(–3%to+12%)聯(lián)合CHD腦卒中聯(lián)合CVD需要住院的GI出血心衰心絞痛冠脈血運重建外周動脈疾病0.51.02.0+23%(+8%to+41%)+6%(0to+12%)+20%(+6%to+37%)-13%(–22%to–4%)+9%(0to+19%)0(–9%to+11%)+19%(+1%to+40%)P=0.055P=0.047P=0.003P=0.007P=0.004P=0.036

終點事件

差別(95%CI)LeenenFHH,etal.Hypertension2006;48:374-384.ALLHAT：賴諾普利vs.氨氯地平相對危險度賴諾普利較好氨氯地平較好+1%(–9%to9

相對危險度(95%CI)培多普利較好安慰劑較好9%(0%to17%)Combinedmacro+micro14%(2%to25%)Alldeaths18%(2%to32%)CVdeathsNonCVdeathsTotalcoronaryTotalcerebrovascularStrokeHeartfailureTotalrenaleventsTotaleyeevents0.51.02.08%(-12%to24%)14%(2to24%)6%(-10%to20%)2%(-18%to19%)21%(15%to27%)5%(-1%to10%)P=0.42

終點事件

差別(95%CI)PatelAetal.Lancet2007;370:829-40.ADVANCE：培多普利vs.安慰劑2%(-20%to19%)P=0.86相對危險度培多普利較好安慰劑較好9%(0%to1710165/1280102/6108218/5571157/128198/6110215/5569PROGRESS/perindoprilonlyEUROPAADVANCE

0.511.52.0培多普利

vs.

安慰劑:致死性與非致死性腦卒中培多普利較好安慰劑較好安慰劑試驗事件數(shù)/研究對象人數(shù)危險比(95%可信區(qū)間)血壓差別(mmHg)培多普利5/25/25.6/2.2PROGRESSManagementCommittee.Lancet200;358:1033-41;FoxKetal.Lancet2003;362:782-8;PatelAetal.Lancet2007;370:829-40.165/1280157/1281PROGRESS/p112.PreventionofMIAmlodipineprovidessimilarprotectionagainstMIasACEIs.心肌梗死預防:氨氯地平

≈

利尿劑/阻滯劑≈

ACEIs

2.PreventionofMI1216/1358154/2213157/547161/31641362/1525517/11571767/28618166/82971933/3691516/1353179/2196183/541077/3157798/904818/11771271/22341133/81791404/305204.5%(3.9)2p=0.261.9%(3.7)2p=0.61MIDAS/NICS/VHASSTOP2/CCBsNORDILINSIGHTALLHAT/AmlodipineELSACCBswithoutCONVINCE p=0.38CONVINCEAllCCBs p=0.140123CCBsvs.

利尿劑/阻滯劑:致死性與非致死性心肌梗死CCBs較好利尿劑/阻滯劑較好利尿劑/阻滯劑試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)CCBsStaessenJA,etal.Lancet2001;37:1305-15.StaessenJAetal.JHypertens2003;21:1055-76.16/135816/13534.5%(3.9)2p=130.200.150.100.050.0001234567基線CHD隨訪時間（年）賴/氨1.06(0.99-1.32)0.69RR(95%Cl)P值0.200.150.100.050.0001234567基線無CHD氨氯地平賴諾普利賴/氨0.98(0.88-1.13)0.78RR(95%Cl)P值ALLHAT:致死/非致死性CHD發(fā)生率隨訪時間（年）LeenenFHH,etal.Hypertension2006;48:374-384.CHD累計發(fā)生率0.200114AHA/ACC高血壓合并冠心病降壓治療建議：

各類降壓藥物的異質(zhì)性RosendorffCetal.Circulation2007;115:2761-88.…Thereisalsocontinuingdebateoverwhetherthereare“classeffects”forantihypertensivedrugsorwhethereachdrugmustbeconsideredindividually.Itisreasonabletoassumethatthereareclasseffectsforthiazide-typediuretics,ACEinhibitors,andARBs,whichhaveahighdegreeofhomogeneityintheirmechanismsofactionandsideeffects.Itisequallyclearthattherearemajordifferencesbetweendrugswithinmoreheterogeneousclassesofagents,suchas-blockersorCCBs.AHA/ACC高血壓合并冠心病降壓治療建議：

各類降壓藥物的153.PrventionofstrokeandMIAmlodipinevs.ARBs腦卒中與心肌梗死預防:氨氯地平

vs.ARBs

3.PrventionofstrokeandMI16PreventionofstrokeandMIbyamlodipineandARBs氨氯地平與ARBs預防卒中與心肌梗死Ameta-analysisofRCTs隨機對照臨床試驗綜合分析WangJGetal.Hypertension2007;50:333-339.PreventionofstrokeandMIby17氨氯地平vs.ARBs*:

腦卒中氨氯地平較好ARBs較好IDNTVALUECASE-J所有試驗p=0.4630/579322/764960/2354412/10,58218/567281/759647/2349346/10,512–15.9%(6.2)2p=0.020.51.01.52.0*厄貝沙坦、纈沙坦、坎地沙坦ARBs氨氯地平試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)WangJGetal.Hypertension2007;50:333-339.氨氯地平vs.ARBs*:腦卒中氨氯地平較好ARBs較18IDNTVALUECASE-JAlltrialsp=0.4051/579369/764917/2354437/10,58233/567281/759618/2349332/10,512–16.7%(6.1)2p=0.010.51.01.52.0氨氯地平vs.ARBs*:MIARBs試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)氨氯地平氨氯地平較好ARBs較好*厄貝沙坦、纈沙坦、坎地沙坦WangJGetal.Hypertension2007;50:333-339.IDNT51/57933/567–16.7%(6.1)19Whydiffer,beyondBPcontrol,orbecauseofbetterBPcontrol?為什么有差別，是“降壓外作用”，還是“高質(zhì)量的降壓才是硬道理”？Whydiffer,beyondBPcontrol,201.LowersystemicBPCentralvs.peripheralBP降低整個動脈系統(tǒng)的血壓:中心動脈壓

vs.肱動脈血壓

1.LowersystemicBP21不同部位的血壓水平有所不同不同部位的血壓水平有所不同22降壓治療與心血管病預防課件2301.02.03.04.05.06.0140135130125120115CAFE研究：外周與中心血壓外周SBP:mean=0.7(-0.4to1.7)mmHg中心SBP:mean=4.3(3.3to5.4)mmHg133.9133.2125.5121.2SBP(mmHg)Timesincerandomisation(years)WilliamsB,etal.Circulation2006;113:1213-1225.阿替洛爾氨氯地平01.02.03.04.05.06.014013513012242.Lower24-hourBPTheroleofmorningsurge降低24小時血壓:晨峰血壓

2.Lower24-hourBP25Pedersenetal.JHypertens2007;25:707-712.Pedersenetal.JHypertens2026MeanSBPdifference(Amlodipine-valsartan,mmHg)16111621-4-3-1012給藥后時間（小時）-2ABPMinVALUE:給藥后24小時內(nèi)收縮壓的差別(氨氯地平vs纈沙坦，n=659)-2.7mmHgP=0.039Pedersenetal.JHypertens2007;25:707-712.MeanSBPdifference(Amlodipin27EarlymorningBPsurge清晨高血壓的風險6:000:0012:0018:00Mulleretal.NEnglJMed1985;313:1315–1322;Marleretal.Stroke1989;20:473–476.020406080100120140160180卒中(per2h)05101520253035404550心肌梗死(perh)Stroke(n=1,167)Myocardialinfarction(n=2,999)TimeofthedayEarlymorningBPsurge清晨高血壓的風險283.Nottoolow,nottoofastTreatpatientsindividually不宜太低，不應太快:應遵循個體化原則3.Nottoolow,nottoofast29MI或卒中發(fā)病率(%)MIStroke60>60to70>70to80>80to90>90to100>100to110>11005101520253035隨訪期間的平均舒張壓

(mmHg)MIandstrokebyaveragefollow-upDBPinINVESTMesserliFH

etal.AnnInternMed2006;144:884–93.MI或卒中發(fā)病率(%)MIStroke60>630高血壓合并冠心病患者降壓治療130/80缺血性心臟病心衰130/80STEMI不穩(wěn)定性心絞痛或NSTEMI130/80or120/80穩(wěn)定性心絞痛not<60mmHgslowly130/80合并冠心病危險因素特別注意降壓速度降壓治療目標血壓(mmHg)冠心病不同階段RosendorffCetal.Circulation2007;115:2761-88.not<60mmHgnot<60mmHgnot<60mmHgnot<60mmHgslowlyslowlyslowlyslowly130/80or120/80高血壓合并冠心病患者降壓治療130/80缺血性心臟病心衰1331高血壓一旦確診，應及早開始降壓治療。降低血壓是抗高血壓治療獲益的關鍵。與利尿劑、阻滯劑、ACEIs以及ARBs相比，CCBs具有較強的腦卒中預防作用。卒中是我國高血壓患者最常見的并發(fā)癥，因此，CCBs應作為我國高血壓患者的基礎性用藥。各種DHP-CCBs之間預防心肌梗死的作用可能存在很大差異。氨氯地平是唯一有證據(jù)顯示與利尿劑、阻滯劑、ACEIs具有相似的預防心肌梗死作用的DHP-CCB。降壓藥物之間的差異很可能僅僅是其降壓質(zhì)量的差異。與其強調(diào)降壓之外的作用，不如強化降壓、降脂、降糖等多重危險因素干預。高血壓一旦確診，應及早開始降壓治療。降低血壓是抗高血壓治療獲32Thankyouverymuch！Thankyouverymuch！33BPreductionandCVprevention

降壓治療與心血管病預防

–關注降壓質(zhì)量，豐富高血壓專業(yè)內(nèi)涵–王繼光上海交通大學醫(yī)學院附屬瑞金醫(yī)院上海市高血壓研究所BPreductionandCVprevention34RelativeriskreductionsbyantihypertensivetreatmentinearlytrialsProgressiontosevereHTCHFStrokeCHDTotalmortalityCVmortality-94％*-53%*-40%*-16%*-13%-21%**P<0.05CollinsR,etal.BrMedBull1994;50:272-298.Relativeriskreductionsbyan35BPLTTC.Lancet2003;362:1527-45.0-5-10-15-20-25-30StrokeCHDCHFTotalmortality-23%-15%-16%-14%－4/3mmHgN＝20888MajorCVevents-15%RelativeriskreductionsbyantihypertensivetreatmentinrecenttrialsBPLTTC.Lancet2003;362:1527-436Do5classesofantihypertensivedrugsdifferinthepreventionofCVcomplications?5大類降壓藥物改善結局的作用有差別嗎?Do5classesofantihypertensi371.PreventionofstrokeCCBsaremoreprotectiveagainststroke.預防卒中:CCBs>利尿劑/阻滯劑>ACEIs

1.Preventionofstroke38CCBsvs.

利尿劑/阻滯劑:致死性與非致死性腦卒中利尿劑/阻滯劑CCBs試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)0CCBs較好123利尿劑/阻滯劑較好MIDAS/NICS/VHASSTOP2/CCBsNORDILINSIGHTALLHAT/AmlodipineELSACCBswithoutCONVINCE p=0.68CONVINCE所有CCBs p=0.3915/1358237/2213196/547174/3164675/1525514/11571211/28618118/82971329/3691519/1353207/2196159/541067/3157377/90489/1177838/22341133/8179971/30520–10.2%(4.8)2p=0.02–7.6%(4.4)2p=0.07StaessenJA,etal.Lancet2001;37:1305-15.StaessenJAetal.JHypertens2003;21:1055-76.CCBsvs.利尿劑/阻滯劑:利尿劑/阻滯劑CCB390ACEIs較好123UKPDSSTOP2/ACEIsCAPPPALLHAT/LisinoprilANBP2所有ACEIs p=0.1617/358237/2213148/5493675/15255107/30391184/2635821/400215/2205189/5492457/9054112/3044994/2019510.2%(4.6)2p=0.03ACEIsvs.

利尿劑/阻滯劑:致死性與非致死性腦卒中利尿劑/阻滯劑試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)CCBs利尿劑/阻滯劑較好StaessenJA,etal.Lancet2001;37:1305-15.StaessenJAetal.JHypertens2003;21:1055-76.0ACEIs較好123UKPDS17/35821/4001040降壓治療與心血管病預防課件41

相對危險度(95%CI)賴諾普利較好氨氯地平較好+1%(–9%to+11%)CHD+5%(–3%to+13%)總死亡率+4%(–3%to+12%)聯(lián)合CHD腦卒中聯(lián)合CVD需要住院的GI出血心衰心絞痛冠脈血運重建外周動脈疾病0.51.02.0+23%(+8%to+41%)+6%(0to+12%)+20%(+6%to+37%)-13%(–22%to–4%)+9%(0to+19%)0(–9%to+11%)+19%(+1%to+40%)P=0.055P=0.047P=0.003P=0.007P=0.004P=0.036

終點事件

差別(95%CI)LeenenFHH,etal.Hypertension2006;48:374-384.ALLHAT：賴諾普利vs.氨氯地平相對危險度賴諾普利較好氨氯地平較好+1%(–9%to42

相對危險度(95%CI)培多普利較好安慰劑較好9%(0%to17%)Combinedmacro+micro14%(2%to25%)Alldeaths18%(2%to32%)CVdeathsNonCVdeathsTotalcoronaryTotalcerebrovascularStrokeHeartfailureTotalrenaleventsTotaleyeevents0.51.02.08%(-12%to24%)14%(2to24%)6%(-10%to20%)2%(-18%to19%)21%(15%to27%)5%(-1%to10%)P=0.42

終點事件

差別(95%CI)PatelAetal.Lancet2007;370:829-40.ADVANCE：培多普利vs.安慰劑2%(-20%to19%)P=0.86相對危險度培多普利較好安慰劑較好9%(0%to1743165/1280102/6108218/5571157/128198/6110215/5569PROGRESS/perindoprilonlyEUROPAADVANCE

0.511.52.0培多普利

vs.

安慰劑:致死性與非致死性腦卒中培多普利較好安慰劑較好安慰劑試驗事件數(shù)/研究對象人數(shù)危險比(95%可信區(qū)間)血壓差別(mmHg)培多普利5/25/25.6/2.2PROGRESSManagementCommittee.Lancet200;358:1033-41;FoxKetal.Lancet2003;362:782-8;PatelAetal.Lancet2007;370:829-40.165/1280157/1281PROGRESS/p442.PreventionofMIAmlodipineprovidessimilarprotectionagainstMIasACEIs.心肌梗死預防:氨氯地平

≈

利尿劑/阻滯劑≈

ACEIs

2.PreventionofMI4516/1358154/2213157/547161/31641362/1525517/11571767/28618166/82971933/3691516/1353179/2196183/541077/3157798/904818/11771271/22341133/81791404/305204.5%(3.9)2p=0.261.9%(3.7)2p=0.61MIDAS/NICS/VHASSTOP2/CCBsNORDILINSIGHTALLHAT/AmlodipineELSACCBswithoutCONVINCE p=0.38CONVINCEAllCCBs p=0.140123CCBsvs.

利尿劑/阻滯劑:致死性與非致死性心肌梗死CCBs較好利尿劑/阻滯劑較好利尿劑/阻滯劑試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)CCBsStaessenJA,etal.Lancet2001;37:1305-15.StaessenJAetal.JHypertens2003;21:1055-76.16/135816/13534.5%(3.9)2p=460.200.150.100.050.0001234567基線CHD隨訪時間（年）賴/氨1.06(0.99-1.32)0.69RR(95%Cl)P值0.200.150.100.050.0001234567基線無CHD氨氯地平賴諾普利賴/氨0.98(0.88-1.13)0.78RR(95%Cl)P值ALLHAT:致死/非致死性CHD發(fā)生率隨訪時間（年）LeenenFHH,etal.Hypertension2006;48:374-384.CHD累計發(fā)生率0.200147AHA/ACC高血壓合并冠心病降壓治療建議：

各類降壓藥物的異質(zhì)性RosendorffCetal.Circulation2007;115:2761-88.…Thereisalsocontinuingdebateoverwhetherthereare“classeffects”forantihypertensivedrugsorwhethereachdrugmustbeconsideredindividually.Itisreasonabletoassumethatthereareclasseffectsforthiazide-typediuretics,ACEinhibitors,andARBs,whichhaveahighdegreeofhomogeneityintheirmechanismsofactionandsideeffects.Itisequallyclearthattherearemajordifferencesbetweendrugswithinmoreheterogeneousclassesofagents,suchas-blockersorCCBs.AHA/ACC高血壓合并冠心病降壓治療建議：

各類降壓藥物的483.PrventionofstrokeandMIAmlodipinevs.ARBs腦卒中與心肌梗死預防:氨氯地平

vs.ARBs

3.PrventionofstrokeandMI49PreventionofstrokeandMIbyamlodipineandARBs氨氯地平與ARBs預防卒中與心肌梗死Ameta-analysisofRCTs隨機對照臨床試驗綜合分析WangJGetal.Hypertension2007;50:333-339.PreventionofstrokeandMIby50氨氯地平vs.ARBs*:

腦卒中氨氯地平較好ARBs較好IDNTVALUECASE-J所有試驗p=0.4630/579322/764960/2354412/10,58218/567281/759647/2349346/10,512–15.9%(6.2)2p=0.020.51.01.52.0*厄貝沙坦、纈沙坦、坎地沙坦ARBs氨氯地平試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)WangJGetal.Hypertension2007;50:333-339.氨氯地平vs.ARBs*:腦卒中氨氯地平較好ARBs較51IDNTVALUECASE-JAlltrialsp=0.4051/579369/764917/2354437/10,58233/567281/759618/2349332/10,512–16.7%(6.1)2p=0.010.51.01.52.0氨氯地平vs.ARBs*:MIARBs試驗事件數(shù)/研究對象人數(shù)異質(zhì)性檢驗危險比(95%可信區(qū)間)差別(SD)氨氯地平氨氯地平較好ARBs較好*厄貝沙坦、纈沙坦、坎地沙坦WangJGetal.Hypertension2007;50:333-339.IDNT51/57933/567–16.7%(6.1)52Whydiffer,beyondBPcontrol,orbecauseofbetterBPcontrol?為什么有差別，是“降壓外作用”，還是“高質(zhì)量的降壓才是硬道理”？Whydiffer,beyondBPcontrol,531.LowersystemicBPCentralvs.peripheralBP降低整個動脈系統(tǒng)的血壓:中心動脈壓

vs.肱動脈血壓

1.LowersystemicBP54不同部位的血壓水平有所不同不同部位的血壓水平有所不同55降壓治療與心血管病預防課件5601.02.03.04.05.06.0140135130125120115CAFE研究：外周與中心血壓外周SBP:mean=0.7(-0.4to1.7)mmHg中心SBP:mean=4.3(3.3to5.4)mmHg133.9133.2125.5121.2SBP(mmHg)Timesincerandomisation(years)WilliamsB,etal.Circulation2006;113:1213-1225.阿替洛爾氨氯地平01.02.03.04.05.06.014013513012572.Lower24-hourBPTheroleofmorningsurge降低24小時血壓:晨峰血壓

2.Lower24