降压治疗与心血管病预防

1、会计学1降压治疗与心血管病预防降压治疗与心血管病预防Progression to severe HTCHFStrokeCHDTotal mortalityCV mortality-94*-53%*-40%*-16%*-13%-21%*P 利尿剂利尿剂/ 阻滞剂阻滞剂 ACEIs CCBs vs. 利尿剂利尿剂/ 阻滞剂阻滞剂: 致死性与非致死性脑卒中致死性与非致死性脑卒中利尿剂利尿剂/ 阻滞剂阻滞剂CCBs试验试验事件数事件数 / 研究对象人数研究对象人数异质性检异质性检验验 危险比危险比 (95%可信区间可信区间)差别差别 (SD)0CCBs较好较好123利尿剂利尿剂/ 阻滞剂较好阻滞剂较好

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较好较好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. 利尿剂利尿剂/ 阻滞

4、剂阻滞剂: 致死性与非致死性脑卒中致死性与非致死性脑卒中利尿剂利尿剂/ 阻滞剂阻滞剂试验试验事件数事件数 / 研究对象人数研究对象人数异质性检异质性检验验 危险比危险比 (95%可信区间可信区间)差别差别 (SD)CCBs利尿剂利尿剂/ 阻滞剂较好阻滞剂较好Staessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76. 相对危险度相对危险度(95% CI)赖诺普利赖诺普利较好较好氨氯地平氨氯地平较好较好 +1% (9% to +11%)CHD +5% (3% to +13%)

5、 总死亡率总死亡率 +4% (3% to +12%) 联合联合CHD 脑卒中脑卒中 联合联合CVD 需要住院的需要住院的GI出血出血心衰心衰 心绞痛心绞痛 冠脉血运重建冠脉血运重建 外周动脉疾病外周动脉疾病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 终点事件终点事件 差别差别 (

6、95% CI)Leenen FHH, et al. Hypertension 2006;48:374-384.ALLHAT：赖诺普利：赖诺普利 vs. 氨氯地平氨氯地平 相对危险度相对危险度(95% CI)培多普利培多普利较好较好安慰剂安慰剂较好较好 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 终点事件终点事件 差别差别 (95% CI)Patel A et al. Lancet 2007; 370:829-40.ADVANCE：培多普利：培多普利 vs. 安慰剂安慰剂 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. 安慰剂安慰剂: 致死性与非致死性脑卒中致死性与非致死性脑卒中培多普利较好培多普利较好安慰安慰剂较好剂较好安慰剂安慰剂试验试验事件数事件数 / 研究对象人数研究对象人数危险比危险比 (95%可信区间可信区间)血压差别血压差别 (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.心肌梗死预防心肌梗死预防: 氨氯地平氨氯地平 利尿剂利尿剂/ 阻滞剂阻滞剂 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. 利尿剂利尿剂/ 阻滞剂阻滞剂: 致死性与非致死性心肌梗死致死性与非致死性心肌梗死CCBs较好较好利尿剂利尿剂/ 阻滞剂较好阻滞剂较好利尿剂利尿剂/ 阻滞剂阻滞剂试验试验事件数事件数 / 研究对象人数研究对象人数异质性检异质性检验验 危险比危险比 (95%可信区间可信区间)差别差别 (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基线CHD随访时间（年）赖/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基线无CHD氨氯地平赖诺普利赖/氨 0.98(0.88-1.13) 0.78RR(95%Cl) P 值ALLHAT: 致死致死/非致死性非致死性CHD发生率发生率随访时间（年）Leenen F

12、HH, et al. Hypertension 2006;48:374-384.CHD累计发生率累计发生率AHA/ACC高血压合并冠心病降压治疗建议高血压合并冠心病降压治疗建议：各类降压药物的异质性各类降压药物的异质性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脑卒中与心肌梗死预防脑卒中与心肌梗死预防: 氨氯地平氨氯地平 vs. ARBs A meta-analysis of RCTs随机对照临床试验综合分析随机对照临床试验综合分析Wang JG et al. Hypertension 2007; 50: 333-339. 氨氯地平氨氯地平 vs. ARBs*: 脑卒中脑卒中氨氯地平较好氨氯地平较好ARBs较好较好IDNT VALUECASE-J所有试验所有试验 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* 厄贝沙坦、厄贝沙坦、缬沙坦、坎地沙坦缬沙坦、坎地沙坦ARBs氨氯地平氨氯地平试验试验事件数事件数 / 研究对象人数研究对象人数异质性检验异质性检验 危险比危险比 (95%可信区间可信区间)差别差别 (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试验试验事件数事件数 / 研究对象人数研究对象人数异质性检验异质性检验 危险比危险比 (95%可信区间可信区间)差别差别 (SD)氨氯地平氨氯地平氨氯地平较好氨氯地平较好ARBs较好较好* 厄贝沙坦、厄贝沙坦、缬沙坦、坎地沙坦缬沙坦、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 ? 为什么有差别，是为什么有差别，是“降压外作用降压外作用”，还是，还是“高高质量的降压才是硬道理质量的降压才是硬道理”？Central vs. peripheral BP降低整个动脉系统的血压降低整个动脉系统的血压: 中心动脉压中心动脉压 vs. 肱动脉血压肱动脉血压 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.阿替洛尔阿替洛尔 氨氯地平氨氯地平 The role of morning surge 降低降低24小时血压小时血压: 晨峰血压晨峰血压 Pedersen et al. J Hypertens 2007;25:707-712.Mean SBP difference (Amlodipine-valsartan, mm Hg)16111621-4-3-1012给药后时间（小时）给药后时间（小时）-2ABPM in VALUE: 给药后24小时内收缩压的

19、差别(氨氯地平 vs 缬沙坦，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，不应太快不宜太低，不应太快: 应遵循个体化原则应遵循个体化原则MIMI或卒或卒中发病中发病率率(%)(%)MI Stroke6060 to 7070 to 8080 to 9090 to 100100 to 110 11005101520253035随访期间的平均舒张压随访期间的平均舒张压 (mm Hg)Messerli FH et al. Ann Intern Med 2006;144:88493.130/80缺血性心脏病心衰缺血性心脏病心衰130/80STEMI

21、不稳定性心绞痛或不稳定性心绞痛或NSTEMI130/80 or 120/80稳定性心绞痛稳定性心绞痛not 60 mm Hgslowly130/80合并冠心病危险因素合并冠心病危险因素特别特别注意注意降压降压速度速度降压治疗目标降压治疗目标血压血压(mm Hg)冠心病不同阶段冠心病不同阶段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