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1、高血压优化治疗方案研究进展,王 文 卫生部心血管病防治中心 中国医学科学院阜外医院,全球高血压状况 (WHO),全球10亿高血压患者 (中国2亿人） 全球710 万 人由于血压升高而过早死亡 （中国150万人） 亚太队列表明66%心脑血管病发生与高血压有关 中国每年300万人死于心血管病 全国高血压人群知晓率30%，治疗率25%，控制率6%,我国城市居民主要疾病死亡率变化,1/10万人,高血压作为慢性病控制切入点 的背景和依据,高血压病人多: 2亿人 高血压危害大: 是心脑血管病最主要危险因素 高血压检查与随访监测方法简单 高血压治疗证据较多 高血压治疗效价好,社会和经济效益好 高血压相对容易
2、控制 高血压疗效评价方法简单 病人、医生、领导、社区易见到成绩,我国慢性病发病及就诊情况 -2007中国心血管病报告,估计我国心血管病现患2亿3千万人 每年新发脑卒中200万，现存1300万人 每年新发心梗50万，现存300万人；冠心病800万人 2003年慢性病就诊人数共5.74亿人次： 糖尿病 0.33亿人次- 恶性肿瘤 0.46亿人次- 脑血管病 0.93亿人次- 心脏病 1.65亿人次- 高血压 2.37亿人次-,2003年心血管病医疗费用(亿元),病种 门诊 住院 合计 高血压 279 87 366 冠心病 133 131 264 脑卒中 207 199 405 肺心病 29 21
3、50 风心病 23 11 34 糖尿病 94 74 168,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 / 肥胖,高血压,高胆固醇,2000全球死亡: Impact of Hypertension and Other Health Risk Factors,Attributable mortality in millions (total: 55,861,000),发展中国家 Developing region 发达国家
4、 Developed region,0,8,7,6,5,4,3,2,1,高血压,吸烟,高胆固醇l,Unsafe sex,High BMI,Physical inactivity,Alcohol,Underweight,Ezzati et al. Lancet 2002;360:134760,Lewington et al. Lancet 2002;360:190313,人群SBP/DBP每升高 20/10 mmHg * 心血管死亡危险 成倍增加,Cardiovascular mortality risk,0,2,4,8,115/75,135/85,155/95,175/105,6,Systol
5、ic BP/Diastolic BP (mmHg),*Individuals aged 4069 years,2X risk,4X risk,8X risk,1X risk,Average no. of antihypertensive medications,1,2,3,4,为血压达标,需要多种降压药联合治疗,Trial (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,ASCO
6、T-BPLA (136.9 mmHg),ALLHAT (138 mmHg),IDNT (138 mmHg),RENAAL (141 mmHg),UKPDS (144 mmHg),ABCD (132 mmHg),MDRD (132 mmHg),HOT (138 mmHg),AASK (128 mmHg),ACCOMPLISH* (132 mmHg),Initial 2-drug combination therapy,*Interim 6-month data,单药治疗与联合治疗策略 -2007年欧洲高血压指南,The preferred combinations in the general
7、hypertensive population are represented as thick lines. The Frames indicate classes of agents proven to be benefical in controlled intervention trials,Journal of Hypertension 2007, Vol 25,No 6 :1144,利尿剂,b-blockers,ARB,a-blockers,CCB,ACEI,实线连接为有效且耐受性好 虚线连接按必要时谨慎使用,联合用药方案 -2007年欧洲高血压指南,近期高血压联合治疗试验,试验
8、优化组合 对照组合 ADVANCE ACEI + D PL O FEVER CCB + D D O HYVET D ACEI PL O ONTARGET ACEI + ARB ACEI O ASCOT CCB + ACEI BK + D ACCOMPLISH ACEI + CCB ACEI + D CHIEF CCB + ARB CCB + D,苯磺酸氨氯地平联合降压治疗 主要临床试验,ASCOT-BPLA: Treatment algorithm for BP targets,19,342 patients 4079 y with U N T R E A T E D SBP 160 mmHg
9、 and/or DBP 100 mmHg OR T R E A T E D SBP 140 mmHg and/or DBP 90 mmHg,In each arm, pts with total cholesterol 6.5 mmol/L randomized to atorvastatin (10 mg) or placebo daily (n = 10,297),RANDOMIZATION,Atenolol 50 mg,Amlo 5 mg,Amlo 10 mg,Atenolol 100 mg,Amlo 10 mg + peri 4 mg,Amlo 10 mg + peri 8 mg (2
10、 x 4 mg),Amlo 10 mg + peri 8 mg (2 x 4 mg) + doxa 4 mg,Amlo 10 mg + peri 8 mg (2 x 4 mg) + doxa 8 mg,Atenolol 100 mg + BFZ 2.5 mg + K+,Atenolol 100 mg + BFZ 2.5 mg + K+ + doxa 4 mg,Atenolol 100 mg + BFZ 1.25 mg + K+,Atenolol 100 mg + BFZ 2.5 mg + K+ + doxa 8 mg,5 Years or 1150 primary events,BP medi
11、cation titrated to achieve target: No diabetes: 140/90 mm Hg Diabetes: 130/80 mm Hg,Sever PS et al. J Hypertens. 2001;19:1139-47.,Amlo = amlodipine; Peri = perindopril; Doxa = doxazosin GITS (Gastrointestinal Transport System); BFZ = bendroflumethiazide,ASCOT-BPLA: Reductions in BP over time,Dahlf B
12、 et al; ASCOT Investigators. Lancet. 2005;366:895-906.,Mean difference = 1.9, P 0.0001,Time (years),Blood pressure (mm Hg),60,100,0,1.0,2.0,3.0,4.0,5.0,Final visit (mean 5.7 SD 0.6, range 4.67.3),0,0.5,1.5,2.5,3.5,4.5,5.5,80,120,140,160,180,Mean difference = 2.7, P 0.0001,Systolic BP,Diastolic BP,13
13、7.7 136.1,79.2 77.4,BP,*Atenolol 50100 mg bendroflumethiazide 1.252.5 mg/potassium prn Amlodipine 510 mg perindopril 48 mg prn,Secondary endpoints Nonfatal MI (excluding silent) 7.4 8.5 + fatal CHD Total coronary endpoint 14.6 16.8 Total CV events and procedures 27.4 32.8 All-cause mortality 13.9 15
14、.5 CV mortality 4.9 6.5 Fatal/nonfatal stroke 6.2 8.1 Fatal/nonfatal HF 2.5 3.0 Tertiary endpoints Development of diabetes 11.0 15.9 Development of renal impairment 7.7 9.1,Rate/1000 patient years,Amlodipine-based* (n = 9639),Atenolol-based (n = 9618),0.05 0.01 0.0001 0.05 0.001 0.001 NS 0.0001 0.05
15、,P,Amlodipine-based better,Atenolol-based better,0.50,0.70,1.00,1.45,2.00,ASCOT-BPLA: Additional reductions in group receiving the amlodipine-based regimen,Unadjusted risk reduction,Rate/1000 patient years,Dahlf B et al; ASCOT Investigators. Lancet. 2005;366:895-906.,*Amlodipine 510 mg perindopril 48 mg prn Atenolol 50100 mg bendroflumethiazide 1.252.5 mg/potassium prn,ACCOMPLISH: 研究设计,Jamerson KA et al. Am J Hypertens. 2003;16(part2)193A,*Beta blockers; alpha blockers; clon
