高血压化治疗方案研究进展王文

1、全球高血压状况 (who) 我国城市居民主要疾病死亡率变化 1/10万人万人高血压作为慢性病控制切入点的背景和依据我国慢性病发病及就诊情况-2007中国心血管病报告2003年心血管病医疗费用(亿元) 不同危险因素与心血管病的归因危险的比较注：调整因素 ：年龄、性别和上述危险因素；*tc6.24mmol/l、hdl-c1.04 mmol/l、糖尿病(fbg7.0 mmol/l)、肥胖（bmi28kg/m2）超重超重 / 肥胖肥胖高血压高血压高胆固醇高胆固醇attributable mortality in millions (total: 55,861,000)发展中国家 developing

2、region发达国家 developed region087654321高血压吸烟 高胆固醇lunsafe sexhigh bmiphysical inactivityalcoholunderweightezzati et al. lancet 2002;360:134760lewington et al. lancet 2002;360:190313cardiovascular mortality risk0248115/75135/85155/95175/1056systolic bp/diastolic bp (mmhg)*individuals aged 4069 years2x ri

3、sk4x risk8x risk1x riskaverage no. of antihypertensive medications1234trial (sbp achieved)bakris et al. am j med 2004;116(5a):30s8 dahlf et al. lancet 2005;366:895906; jamerson et al. blood press 2007;16:806 ascot-bpla (136.9 mmhg)allhat (138 mmhg)idnt (138 mmhg)renaal (141 mmhg)ukpds (144 mmhg)abcd

4、 (132 mmhg)mdrd (132 mmhg)hot (138 mmhg)aask (128 mmhg)accomplish* (132 mmhg)initial 2-drug combination therapy*interim 6-month data两者之间进行选择两者之间进行选择若未达到目标血压若未达到目标血压若未达到目标血压若未达到目标血压将既往用药将既往用药加至足量加至足量换用其他药物，换用其他药物，低剂量治疗低剂量治疗将既往联合用药加至将既往联合用药加至足量足量增加第三种药物，增加第三种药物，低剂量治疗低剂量治疗23种药物联用，种药物联用，足量治疗足量治疗足量足量单药治疗

5、单药治疗23种药物联用，足量治疗种药物联用，足量治疗血压轻度升高血压轻度升高低低/中度心血管风险中度心血管风险常规目标血压常规目标血压血压明显升高血压明显升高高高/极高危极高危较低目标血压较低目标血压 低剂量单药治疗低剂量单药治疗 2种药物联用，低剂量治疗种药物联用，低剂量治疗journal of hypertension 2007, vol 25,no 6 :1144the preferred combinations in the general hypertensive population are represented as thick lines. the frames indic

6、ate classes of agents proven to be benefical in controlled intervention trialsjournal of hypertension 2007, vol 25,no 6 :1144利尿剂利尿剂b b-blockers arb a a-blockersccbacei实线连接为有效且耐受性好实线连接为有效且耐受性好虚线连接按必要时谨慎使用虚线连接按必要时谨慎使用19,342 patients4079 ywithu n t r e a t e dsbp 160 mmhg and/ordbp 100 mmhg ort r e a t

7、 e d sbp 140 mmhg and/or dbp 90 mmhgin each arm, pts with total cholesterol 6.5 mmol/l randomized to atorvastatin (10 mg) or placebo daily(n = 10,297)atenolol50 mgamlo5 mgamlo10 mgatenolol100 mgamlo 10 mg +peri 4 mgamlo 10 mg +peri 8 mg(2 x 4 mg)amlo 10 mg +peri 8 mg(2 x 4 mg) +doxa 4 mgamlo 10 mg +

8、peri 8 mg(2 x 4 mg) +doxa 8 mgatenolol100 mg +bfz 2.5 mg + k+ atenolol100 mg +bfz 2.5 mg + k+ + doxa 4 mgatenolol100 mg +bfz 1.25 mg + k+ atenolol100 mg +bfz 2.5 mg + k+ + doxa 8 mg5 years or 1150 primary eventsbp medication titrated to achieve target: no diabetes: 140/90 mm hg diabetes: 130/80 mm h

9、gsever ps et al. j hypertens. 2001;19:1139-47.amlo = amlodipine; peri = perindopril; doxa = doxazosin gits (gastrointestinal transport system); bfz = bendroflumethiazideatenolol-based regimen*amlodipine-based regimendahlf b et al; ascot investigators. lancet. 2005;366:895-906.mean difference = 1.9,

10、p 0.0001time (years)blood pressure(mm hg)6010001.02.03.04.05.0final visit (mean 5.7 sd 0.6, range 4.67.3) 00.51.52.53.54.55.580120140160180mean difference = 2.7, p 0.0001systolic bpdiastolic bp137.7136.179.277.4 bp*atenolol 50100 mg bendroflumethiazide 1.252.5 mg/potassium prnamlodipine 510 mg perin

11、dopril 48 mg prnsecondary endpointsnonfatal mi (excluding silent)7.4 8.5+ fatal chdtotal coronary endpoint14.6 16.8total cv events and procedures 27.4 32.8 all-cause mortality13.9 15.5 cv mortality4.9 6.5 fatal/nonfatal stroke6.2 8.1 fatal/nonfatal hf2.5 3.0 tertiary endpointsdevelopment of diabetes

12、11.0 15.9 development of renal impairment7.7 9.1 rate/1000patient yearsamlodipine-based*(n = 9639)atenolol-based (n = 9618) 0.05 0.010.0001 0.05 0.001 0.001 ns 0.0001 0.05 pamlodipine-based betteratenolol-based better0.500.701.001.452.00unadjusted risk reductionrate/1000patient yearsdahlf b et al; a

13、scot investigators. lancet. 2005;366:895-906.*amlodipine 510 mg perindopril 48 mg prnatenolol 50100 mg bendroflumethiazide 1.252.5 mg/potassium prnjamerson ka et al. am j hypertens. 2003;16(part2)193atitrated to achieve bp140/90 mmhg; 130/80 mmhg in patients with diabetes or renal insufficiencymm hg

14、month5731538752064999480442852520104557095377515449804831428625941075patientsacei / hctzn=5733ccb / acein=5713*mean values are taken at 30 months f/u visit129.3 mmhg130mmhg差值差值 0.7 mmhg p0.05*dbp: 71.1dbp: 72.8基线基线控制率控制率37.237.9acei / hctzn=5733控制率控制率(%)ccb / acein=571310203040506070809078.5p0.001 随

15、访随访30月时月时对照组为 140/90 mmhg因不稳定性心绞痛入院因不稳定性心绞痛入院冠脉重建术冠脉重建术心脏复苏后猝死心脏复苏后猝死incidence of adjudicated primary endpoints, based upon cut-off analysis date 3/24/2008(intent-to-treat population)favors ccb / aceifavors acei / hctz中期 数据 mar 08p 课题牵头单位：中国医学科学院阜外心血管病医院 p 指导委员会主席：刘力生 课题负责人： 王 文p 主要合作者：朱鼎良 林曙光 黄峻 等

16、180家单位p 研究立项资助： 国家科技部p 组织管理： 国家卫生部p 研究药品资助：东瑞制药公司 研究对伴心血管病危险因素的高血压患者进行综合干预（联合降压，调脂及生活方式干预）的效果，即对心血管事件的影响。 研究比较初始用两种联合降压治疗方案（小剂量钙拮抗剂+血管紧张素ii受体拮抗剂-arb：小剂量钙拮抗剂+利尿剂）对伴心血管病危险因素的高血压患者的效果。 研究比较对血总胆固醇正常偏高的高血压伴高危因素患者进行他汀调脂治疗与常规调脂治疗的效果。 研究比较对社区高血压患者生活方式强化干预（限盐，戒烟，减重，适当运动）与社区常规处理的效果和可行性。主要研究目的主要研究目的-2w 0 2w 4w

17、 2m 3m 6m 9m 12m 24m 36m run-in period randomizationa= 安氯地平安氯地平 （安内真安内真）; t= 替米沙坦替米沙坦 (安内强安内强)d= 复方盐酸阿米洛利复方盐酸阿米洛利（ 安利亚安利亚）chief 研究方案a 2.5mg + t 40mga 2.5mg + d taba 2.5mg + d 1 taba 5mg +d1 tabadd other antihypertensive agentsa 2.5mg + t80mga 5mg + t 80mgadd other antihypertensive agents w: week； m:

18、 monthsbp/dbp target140/90mmhg for general hypertensive130/80mmhg for diabetes or nephropathy(dosage will be titrated for uncontrolled hypertension)run-in control rateweeks70%a+ta+dto：2008/7/1542.33%41.02%57.72% 56.71%72.39% 70.40%77.63%78.26%a+ta+d a: amlodipine. d: diuretics, t: telmisartanto：2008

19、/7/15sbp （mmhg）dbp(mmhg)ccb arteriodilation peripheral edema effective in low-renin patients reduces cardiac ischemia ccb ras activation no renal or chf benefitsarb venodilation attenuates peripheral edema effective in high-renin patients no effect on cardiac ischemiaarb ras blockade chf and renal b

20、enefits messerli et al. am j hypertens 2001;14:9789arterialdilation(ccb andarb)venousdilation(arb)capillary bedccb dilates arteriesveins remain constrictedarb dilates arteries and veinssingle mode of action of the ccbdual mode of action of the ccbarb capillary overload forces fluid into surrounding tissuereduces ccb-induced peripheral edemaillustration modified from messerli et al. am j hypertens 2001;14:9789amlodipine/valsartan 5/160 mgamlodipine/valsartan 10/160 mgdiabetic patients with bp 130/80 mmhg at week 8 were 47.0% and 49.2% for 5/160 mg and 10/160 mg doses, respectivelypat