降壓治療與心血管病預(yù)防

1、會計學(xué)1降壓治療與心血管病預(yù)防降壓治療與心血管病預(yù)防Progression to severe HTCHFStrokeCHDTotal mortalityCV mortality-94*-53%*-40%*-16%*-13%-21%*P 利尿劑利尿劑/ 阻滯劑阻滯劑 ACEIs CCBs vs. 利尿劑利尿劑/ 阻滯劑阻滯劑: 致死性與非致死性腦卒中致死性與非致死性腦卒中利尿劑利尿劑/ 阻滯劑阻滯劑CCBs試驗試驗事件數(shù)事件數(shù) / 研究對象人數(shù)研究對象人數(shù)異質(zhì)性檢異質(zhì)性檢驗驗 危險比危險比 (95%可信區(qū)間可信區(qū)間)差別差別 (SD)0CCBs較好較好123利尿劑利尿劑/ 阻滯劑較好阻滯劑較好

2、MIDAS/NICS/VHASSTOP2/CCBsNORDILINSIGHTALLHAT/AmlodipineELSACCBs without CONVINCE p = 0.68CONVINCE所有所有CCBsp = 0.3915/1358237/2213196/547174/3164675/1525514/11571211/28618118/82971329/3691519/1353207/2196159/541067/3157377/90489/1177838/22341133/8179971/3052010.2% (4.8) 2p = 0.027.6% (4.4) 2p = 0.07St

3、aessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76. 0ACEIs較好較好123UKPDSSTOP2/ACEIsCAPPPALLHAT/LisinoprilANBP2所有所有ACEIsp = 0.1617/358237/2213148/5493675/15255107/30391184/2635821/400215/2205189/5492457/9054112/3044994/2019510.2% (4.6) 2p = 0.03ACEIs vs. 利尿劑利尿劑/ 阻滯

4、劑阻滯劑: 致死性與非致死性腦卒中致死性與非致死性腦卒中利尿劑利尿劑/ 阻滯劑阻滯劑試驗試驗事件數(shù)事件數(shù) / 研究對象人數(shù)研究對象人數(shù)異質(zhì)性檢異質(zhì)性檢驗驗 危險比危險比 (95%可信區(qū)間可信區(qū)間)差別差別 (SD)CCBs利尿劑利尿劑/ 阻滯劑較好阻滯劑較好Staessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76. 相對危險度相對危險度(95% CI)賴諾普利賴諾普利較好較好氨氯地平氨氯地平較好較好 +1% (9% to +11%)CHD +5% (3% to +13%)

5、 總死亡率總死亡率 +4% (3% to +12%) 聯(lián)合聯(lián)合CHD 腦卒中腦卒中 聯(lián)合聯(lián)合CVD 需要住院的需要住院的GI出血出血心衰心衰 心絞痛心絞痛 冠脈血運重建冠脈血運重建 外周動脈疾病外周動脈疾病0.51.02.0 +23% (+8% to +41%) +6% ( 0 to +12%) +20% (+6% to +37%) -13% (22% to 4%) +9% ( 0 to +19%) 0 (9% to +11%) +19% (+1% to +40%) P=0.055 P=0.047 P=0.003 P=0.007 P=0.004 P= 0.036 終點事件終點事件 差別差別 (

6、95% CI)Leenen FHH, et al. Hypertension 2006;48:374-384.ALLHAT：賴諾普利：賴諾普利 vs. 氨氯地平氨氯地平 相對危險度相對危險度(95% CI)培多普利培多普利較好較好安慰劑安慰劑較好較好 9% (0% to 17%)Combined macro+micro 14% (2% to 25%) All deaths 18% (2% to 32%) CV deathsNon CV deaths Total coronary Total cerebrovascularStrokeHeart failure Total renal event

7、s Total eye events0.51.02.0 8% (-12% to 24%) 14% (2 to 24%) 6% (-10% to 20%) 2% (-18% to 19%) 21% (15% to 27%) 5% (-1% to 10%) P=0.42 終點事件終點事件 差別差別 (95% CI)Patel A et al. Lancet 2007; 370:829-40.ADVANCE：培多普利：培多普利 vs. 安慰劑安慰劑 2% (-20% to 19%) P=0.86 165/1280102/6108218/5571157/128198/6110215/5569PROGR

8、ESS/perindopril onlyEUROPAADVANCE 0.511.52.0培多普利培多普利 vs. 安慰劑安慰劑: 致死性與非致死性腦卒中致死性與非致死性腦卒中培多普利較好培多普利較好安慰安慰劑較好劑較好安慰劑安慰劑試驗試驗事件數(shù)事件數(shù) / 研究對象人數(shù)研究對象人數(shù)危險比危險比 (95%可信區(qū)間可信區(qū)間)血壓差別血壓差別 (mm Hg)培多普利培多普利5/25/25.6/2.2PROGRESS Management Committee. Lancet 200;358:1033-41; Fox K et al. Lancet 2003;362:782-8; Patel A et a

9、l. Lancet 2007; 370:829-40.Amlodipine provides similar protection against MI as ACEIs.心肌梗死預(yù)防心肌梗死預(yù)防: 氨氯地平氨氯地平 利尿劑利尿劑/ 阻滯劑阻滯劑 ACEIs 16/1358154/2213157/547161/31641362/1525517/11571767/28618166/82971933/3691516/1353179/2196183/541077/3157798/904818/11771271/22341133/81791404/305204.5% (3.9) 2p = 0.261.

10、9% (3.7) 2p = 0.61MIDAS/NICS/VHASSTOP2/CCBsNORDILINSIGHTALLHAT/AmlodipineELSACCBs without CONVINCE p = 0.38CONVINCEAll CCBsp = 0.140123CCBs vs. 利尿劑利尿劑/ 阻滯劑阻滯劑: 致死性與非致死性心肌梗死致死性與非致死性心肌梗死CCBs較好較好利尿劑利尿劑/ 阻滯劑較好阻滯劑較好利尿劑利尿劑/ 阻滯劑阻滯劑試驗試驗事件數(shù)事件數(shù) / 研究對象人數(shù)研究對象人數(shù)異質(zhì)性檢異質(zhì)性檢驗驗 危險比危險比 (95%可信區(qū)間可信區(qū)間)差別差別 (SD)CCBsStaesse

11、n JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76. 0.200.150.100.050.000 1 2 3 4 5 6 7基線CHD隨訪時間（年）賴/氨 1.06(0.99-1.32) 0.69RR(95%Cl) P 值0.200.150.100.050.000 1 2 3 4 5 6 7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A(chǔ)LLHAT: 致死致死/非致死性非致死性CHD發(fā)生率發(fā)生率隨訪時間（年）Leenen F

12、HH, et al. Hypertension 2006;48:374-384.CHD累計發(fā)生率累計發(fā)生率AHA/ACC高血壓合并冠心病降壓治療建議高血壓合并冠心病降壓治療建議：各類降壓藥物的異質(zhì)性各類降壓藥物的異質(zhì)性Rosendorff C et al. Circulation 2007;115:2761-88.There is also continuing debate over whether there are “class effects” for antihypertensive drugs or whether each drug must be considered indi

13、vidually. It is reasonable to assume that there are class effects for thiazide-type diuretics, ACE inhibitors, and ARBs, which have a high degree of homogeneity in their mechanisms of action and side effects. It is equally clear that there are major differences between drugs within more heterogeneou

14、s classes of agents, such as -blockers or CCBs. Amlodipine vs. ARBs腦卒中與心肌梗死預(yù)防腦卒中與心肌梗死預(yù)防: 氨氯地平氨氯地平 vs. ARBs A meta-analysis of RCTs隨機對照臨床試驗綜合分析隨機對照臨床試驗綜合分析Wang JG et al. Hypertension 2007; 50: 333-339. 氨氯地平氨氯地平 vs. ARBs*: 腦卒中腦卒中氨氯地平較好氨氯地平較好ARBs較好較好IDNT VALUECASE-J所有試驗所有試驗 p = 0.4630/579322/764960/235

15、4412/10,58218/567281/759647/2349346/10,51215.9% (6.2) 2p = 0.020.51.01.52.0* 厄貝沙坦、厄貝沙坦、纈沙坦、坎地沙坦纈沙坦、坎地沙坦ARBs氨氯地平氨氯地平試驗試驗事件數(shù)事件數(shù) / 研究對象人數(shù)研究對象人數(shù)異質(zhì)性檢驗異質(zhì)性檢驗 危險比危險比 (95%可信區(qū)間可信區(qū)間)差別差別 (SD)Wang JG et al. Hypertension 2007; 50:333-339. IDNT VALUECASE-JAll trials p = 0.4051/579369/764917/2354437/10,58233/56728

16、1/759618/2349332/10,51216.7% (6.1) 2p = 0.010.51.01.52.0氨氯地平氨氯地平 vs. ARBs*: MIARBs試驗試驗事件數(shù)事件數(shù) / 研究對象人數(shù)研究對象人數(shù)異質(zhì)性檢驗異質(zhì)性檢驗 危險比危險比 (95%可信區(qū)間可信區(qū)間)差別差別 (SD)氨氯地平氨氯地平氨氯地平較好氨氯地平較好ARBs較好較好* 厄貝沙坦、厄貝沙坦、纈沙坦、坎地沙坦纈沙坦、坎地沙坦Wang JG et al. Hypertension 2007; 50:333-339. Why differ, beyond BP control, or because of better

17、 BP control ? 為什么有差別，是為什么有差別，是“降壓外作用降壓外作用”，還是，還是“高高質(zhì)量的降壓才是硬道理質(zhì)量的降壓才是硬道理”？Central vs. peripheral BP降低整個動脈系統(tǒng)的血壓降低整個動脈系統(tǒng)的血壓: 中心動脈壓中心動脈壓 vs. 肱動脈血壓肱動脈血壓 01.02.03.04.05.06.0140135130125120115外周外周SBP: mean =0.7 (-0.4 to 1.7) mm Hg中心中心SBP: mean =4.3 (3.3 to 5.4) mm Hg133.9133.2125.5121.2SBP (mm Hg) Time sin

18、ce randomisation (years)Williams B, et al. Circulation 2006;113:1213-1225.阿替洛爾阿替洛爾 氨氯地平氨氯地平 The role of morning surge 降低降低24小時血壓小時血壓: 晨峰血壓晨峰血壓 Pedersen et al. J Hypertens 2007;25:707-712.Mean SBP difference (Amlodipine-valsartan, mm Hg)16111621-4-3-1012給藥后時間（小時）給藥后時間（小時）-2ABPM in VALUE: 給藥后24小時內(nèi)收縮壓的

19、差別(氨氯地平 vs 纈沙坦，n=659)-2.7mmHgP=0.039Pedersen et al. J Hypertens 2007;25:707-712.Early morning BP surge6:000:0012:0018:00Muller et al. N Engl J Med 1985;313:13151322; Marler et al. Stroke 1989;20:473476.020406080100120140160180卒中 (per 2 h)05101520253035404550心肌梗死 (per h)Stroke (n=1,167)Myocardial inf

20、arction (n=2,999)Time of the dayTreat patients individually 不宜太低，不應(yīng)太快不宜太低，不應(yīng)太快: 應(yīng)遵循個體化原則應(yīng)遵循個體化原則MIMI或卒或卒中發(fā)病中發(fā)病率率(%)(%)MI Stroke6060 to 7070 to 8080 to 9090 to 100100 to 110 11005101520253035隨訪期間的平均舒張壓隨訪期間的平均舒張壓 (mm Hg)Messerli FH et al. Ann Intern Med 2006;144:88493.130/80缺血性心臟病心衰缺血性心臟病心衰130/80STEMI

21、不穩(wěn)定性心絞痛或不穩(wěn)定性心絞痛或NSTEMI130/80 or 120/80穩(wěn)定性心絞痛穩(wěn)定性心絞痛not 60 mm Hgslowly130/80合并冠心病危險因素合并冠心病危險因素特別特別注意注意降壓降壓速度速度降壓治療目標(biāo)降壓治療目標(biāo)血壓血壓(mm Hg)冠心病不同階段冠心病不同階段Rosendorff C et al. Circulation 2007;115:2761-88.not 60 mm Hgnot 60 mm Hgnot 60 mm Hgnot 60 mm Hgslowlyslowlyslowlyslowly130/80 or 120/80BPLTTC. Lancet 2003;362:1527-45.0-5-10-15-20-25-30StrokeCHDCHFTotal mortality -23%-15%-16%-14%4/3 mmHgN20 888Major CV events