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1、高风险高血压患者的 降压治疗,上海交通大学医学院附属瑞金医院 上海市高血压研究所 王继光 ,指南推荐,利尿剂 阻滞剂 钙离子拮抗剂 转换酶抑制剂 血管紧张素受体拮抗剂 疗效： D CCBs ACEIs/ARBs BB 耐受性：CCBs ARBs ACEIs D BB 容量依赖性 肾素依赖性 心衰 难治性高血压 冠心病,J Hypertens 2007;25:1105-87.,选择联合降压治疗方案 选择长效降压药物 选择血管活性降压药物 高心血管风险患者的控制血压的速度与幅度,Awareness, treatment and control rate of hypertension in Chi
2、na,The 2005 Guidelines for Prevention and Treatment of Hypertension in China.,Number No. drugs 2 drugs ALLHAT 42,424 1.8 40% ANBP2 6083 2.0 50% ASCOT 19,257 2.3 78% CONVINCE 16,602 1.8 40% INVEST 22,576 3.0 85% LIFE 9193 2.0 46% VALUE 15,245 2.0 54%,Number of drugs in recent large HT trials,Achieved
3、 135/76 147/82 136/77 136/79 131/76 144/81 138/78,Possible combinations of antihypertensive drugs,J Hypertens 2007;25:1105-87.,Thiazide diuretics,ACEIs,ARBs,CCBs,-blockers,-blockers,ACCOMPLISH: 主要终点及组成,复合CV发病率/死亡率 心血管死亡率 非致死性心梗 非致死性中风 不稳定心绞痛住院 冠状动脉成形术 猝死复苏成功,主要终点发生率, 2008-3-24统计分析 （按治疗分组）,危险比 (95%),
4、CCB / ACEI较好,0.80 (0.720.90) 0.81 (0.62-1.06) 0.81 (0.63-1.05) 0.87 (0.67-1.13) 0.74 (0.49-1.11) 0.85 (0.74-0.99) 1.75 (0.73-4.17),ACEI / HCTZ较好,Jamerson K. ACC 2008, Chicago.,ASCOT-BPLA：一、二级终点,0.50,0.70,1.00,1.45,主要终点 非致死性MI(包括症状MI)+致死性冠心病 次要终点 非致死性MI(除外无症状MI)+ 致死性冠心病 总的冠心病终点事件 总的心血管病事件和操作 总死亡率 心血管
5、病死亡率 致死性和非致死性脑卒中 致死性和非致死性心力衰竭,2.00,Unadjusted Hazard ratio (95% CI) 0.90 (0.79-1.02) 0.87 (0.76-1.00) 0.87 (0.79-0.96) 0.84 (0.78-0.90) 0.89 (0.81-0.99) 0.76 (0.65-0.90) 0.77 (0.66-0.89) 0.84 (0.66-1.05),Dahlf B et al. Lancet 2005:366;895-906.,氨氯地平 培哚普利较好,阿替洛尔 苄氟噻嗪较好,ONTARGET: Primary endpoint and c
6、omponents,Composite CV mortality/morbidity CV mortality, MI and stroke MI Stroke Hospitalization for heart failure CV mortality Non-CV mortality All cause mortality,Risk Ratio (95%),Favors Ramipril + Telmisartan,Favors Ramipril,0.99 (0.921.07) 1.00 (0.93-1.09) 1.08 (0.94-1.23) 0.93 (0.81-1.07) 0.95
7、(0.82-1.10) 1.04 (0.93-1.17) 1.10 (0.96-1.26) P=0.17 1.07 (0.98-1.16) P=0.12,The ONTARGET Investigators. N Engl J Med 2008;358:1547-59.,-10% +10%,ONTARGET: Secondary and other endpoints,Revascularisation Hospitalisation for angina Worsening or new angina New diagnosis of diabetes Any heart failure N
8、ew atrial fibrillation Renal impairment Renal impairment requiring dialysis,Risk Ratio (95%),Favors Ramipril+Telmisartan,Favors Ramipril,1.04 (0.971.13) 1.04 (0.95-1.14) 0.96 (0.85-1.08) 0.91 (0.78-1.06) 0.94 (0.83-1.07) 0.96 (0.85-1.07) 1.33 (1.22-1.44) 1.37 (0.94-1.98),The ONTARGET Investigators.
9、N Engl J Med 2008;358:1547-59.,-10% +10%,选择联合降压治疗方案 选择长效降压药物 选择血管活性降压药物 高心血管风险患者的控制血压的速度与幅度,Non-dippers,150,140,130,120,110,100,90,80,70,60,50,135,120,85,70,BP (mm Hg),24-h BP profiles,n=260,n=310,Day-night hypertension,Normotension,Hour of the day,BP (mm Hg),BP (mm Hg),135,120,85,70,135,120,85,70,L
10、i Y, et al. Hypertension 2007;50: 333-339.,Early morning BP surge,清晨高血压的风险,6:00,0:00,12:00,18:00,Muller et al. N Engl J Med 1985;313:13151322; Marler et al. Stroke 1989;20:473476.,0,20,40,60,80,100,120,140,160,180,卒中 (per 2 h),0,5,10,15,20,25,30,35,40,45,50,心肌梗死 (per h),Stroke (n=1,167),Myocardial i
11、nfarction (n=2,999),Time of the day,选择联合降压治疗方案 选择长效降压药物 选择血管活性降压药物 高心血管风险患者的控制血压的速度与幅度,不同部位的血压水平有所不同,CAFE研究：外周与中心血压,外周SBP: mean =0.7 (-0.4 to 1.7) mm Hg,中心SBP: mean =4.3 (3.3 to 5.4) mm Hg,133.9 133.2 125.5 121.2,SBP (mm Hg),Time since randomisation (years),Williams B, et al. Circulation 2006;113:12
12、13-1225.,阿替洛尔 氨氯地平,Koshiyama Topouchian Pontremoli Stanton ELVERA All trials Heterogeneity 2 = 4.5 P = 0.34,*ACEIs:CCBs,Trial,Difference (m/y, 95% CI),Favours CCBs,Favours ACEIs,-100,0,100,-23 (-42 to -4) p = 0.02,11:11 18:21 16:15 34:35 63:63 142:145,n*, : 680:720 820:840 792:763 1057:1019,Baseline
13、 IMT (m)*,Change/y (m)*,22:-104 -80:-40 -65:-110 -27:-48 0:-17,-50,50,CCBs vs ACEIs on IMT,Wang JG, et al. Stroke 2006;37:1933.,Nissen et al, for the CAMELOT investigators. JAMA. 2004;292:2217-2226.,安慰剂 (n=49),依那普利 (n=40),氨氯地平 (n=47),P.001,P=0.20,P=0.76,P=0.02,0,0.4,0.8,1.2,1.6,2.0,2.4,所有随机化的患者 N=27
14、4,基线血压 均值的患者 N=136,0,0.4,0.8,1.2,1.6,2.0,2.4,安慰剂 (n=95),依那普利 (n=88),氨氯地平 (n=91),粥样斑块体积百分比的改变 (%),P.001,P=0.08,P=0.31,P=0.12,NORMALISE: IVUS 动脉粥样硬化斑块体积,Glomerular effects of CCBs and ACEIs,Valentino VA et al. Arch Intern Med. 1991;151:2367-2372. Vivian EM et al. Ann Pharmacother. 2001;35:452-463.,Dil
15、ation of afferent arteriole mainly,Dilation of both afferent and efferent arteriole, Glomerular pressure Albumin excretion rate, Glomerular pressure Albumin excretion rate,Efferent arteriole,Glomerulus,DHP/CCB,ACE inhibitor,Bowmans capsule,Afferent arteriole,Efferent arteriole,Afferent arteriole,Glo
16、merulus,Bowmans capsule,相对危险度 (95% CI),赖诺普利较好,氨氯地平较好,+1% (9% to +11%),CHD,+5% (3% to +13%),总死亡率,+4% (3% to +12%),联合CHD,脑卒中,联合CVD,需要住院的GI出血,心衰,心绞痛,冠脉血运重建,外周动脉疾病,0.5,1.0,2.0,+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=0.0
17、55,P=0.047,P=0.003,P=0.007,P=0.004,P= 0.036,终点事件,差别 (95% CI),Leenen FHH, et al. Hypertension 2006;48:374-384.,ALLHAT：赖诺普利 vs. 氨氯地平,98/ 82/ 87/ 52/52 48/44 30/28 80/60,144/ 104/ 83/ 37/37 29/27 18/15 143/93,Doubling of serum creatinine ESRD Death from any cause CV death Myocardial infarction Stroke C
18、HF,0.25,0.5,1.0,2.0,Renal and CV outcomes in IDNT: amlodipine vs irbesartan,Amlodipine较好,Irbesartan较好,Irbesartan,研究终点,事件数 / 患病人数,危险比 (95%可信区间),P,Amlodipine,Lewis EJ et al. N Engl J Med 2001;345:851-60. Berl T et al. Ann Intern Med 2003;138:542-9.,0.001 0.07 0.80 0.16 0.07 0.17 0.004,选择联合降压治疗方案 选择长效降
19、压药物 选择血管活性降压药物 高心血管风险患者的控制血压的速度与幅度,高血压合并冠心病患者降压治疗,130/80,缺血性心脏病心衰,130/80,STEMI,不稳定性心绞痛或NSTEMI,130/80 or 120/80,稳定性心绞痛,not 60 mm Hg,slowly,130/80,合并冠心病危险因素,特别注意,降压速度,降压治疗目标血压(mm Hg),冠心病不同阶段,Rosendorff C et al. Circulation 2007.,not 60 mm Hg,not 60 mm Hg,not 60 mm Hg,not 60 mm Hg,slowly,slowly,slowly,
20、slowly,130/80 or 120/80,佐田登志夫，齋藤宏暢. 日薬理誌（Folia Pharmacol Jpn）2003;122:539-47.,Pharmacodynamic profile of the 3rd and 2nd generations of CCBs,应选择指南推荐的降压药物，使用有效剂量，单独或联合，努力实现降压达标，甚至达到理想血压水平。联合治疗应在实现降压达标的同时，更有效地预防心脑血管并发症，避免严重不良反应。 应尽可能选择起效和缓、作用时间长、一次服药能够有效控制24小时血压、又具有抗动脉硬化与动脉粥样硬化作用的降压药物，不仅有效、平稳地把血压控制到达标甚至理想水平，又要尽最大可能避免大幅度的血压波动。 在使用任何降压药物治疗的过程中，都应注意准确地测量血压，密切监测血压的变化，如果可能，直接观察血管的结构与功能。,Thank you very much ！,