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1、降压治疗研究新动向 强化、优化和简化,扩展降压治疗能获益的人群，当前主要聚焦在80岁以上高龄高血压患者和血压水平140/90的心血管高危患者(心、脑血管病与糖尿病)。,新动向(一),The results of this trial should provide reliable evidence about the effects of blood-pressure-lowering therapy in this very high-risk population.,安慰剂,纳催离缓释片 雅施达 安慰剂,HYVET: 总死亡率,总死亡率降低21%,随访时间（年）,百分率%,纳催离缓释片 雅
2、施达,1912 1933,1492 1565,814 877,379 420,202 231,从HYVET到临床实践, 适用于收缩压160mmHg以上，一般状况尚好，生活能自理，认知功能无明显减退的高龄高血压患者。 降压速度应该相对较平缓，避免体位性低血压。血压控制目标值150/80mmHg。,RAS阻滞剂治疗心血管高危患者 循证证据,HOPE (Ramipril,2000) PROGRESS (Perindopril, 2001) EUROPA (Perindopril, 2003) ADVANCE (Perin/Indap, 2007) ONTARGET (Telmisartan, 200
3、8),HOPE 139/79 3/3 PROGRESS 147/86 9/4 EUROPA 137/82 5/2 ADVANCE 145/81 5/3 ONTARGET 142/82 6/4,基线血压 血压,RAS阻滞剂治疗心血管高危患者 基线血压与血压下降幅度,mmHg,HT,NT,S,D,159.0,159.0,94.0,91.0,136.0,127.2,79.0,74.8,Blood Pressure values in PROGRESS,在心血管高危患者, 强化血压控制。血压控制目标值130/80mmHg正在不断获得循证证据。,新动向(二),SBP,From UKPDS to ADVA
4、NCE,ACCORD Study Action to Control Cardiovascular risk in Diabetes,Prisant LM. J Clin Pharmacol 2004; 44(4):423-430, HbA1c: 6.0% vs 7.0-7.9% (因强化治疗总死亡率增加,08年2月7日宣布提前中止) SBP: 120 mmHg vs 140 mmHg,Arima H, et al. J Hypertens. 2006;24:1201-1208,PROGRESS:,100,80,60,40,20,0,120,120-139,140-159,60,100,80,
5、60,40,20,0,70,70-79,80-89,90,Achieved systolic blood pressure levels (mmHg),Achieved systolic blood pressure levels (mmHg),Age-and sex-adjusted incidence rate,CKD: P trend=0.004 Non-CKD: P trend0.0001,CKD: P trend=0.001 Non-CKD: P trend0.0001,CKD Non-CKD,Incidence rate (1000 person-years),PROGRESS C
6、KD Substudy: SBP and CVD,Messerli FH, et al. Ann Intern Med. 2006;144:884-893,冠心病患者血压控制水平与心血管危险,Rosendorff C, et al. Circulation 2007;115:,Treatment of Hypertension in IHD A Scientific Statement from AHA, 2007.4, 冠心病患者需要积极控制血压，合理的血压控 制目标值130/80mmHg。（a,B） 应该相对缓慢降低血压，避免DBP60mmHg。,优化降压治疗方案，比较不同降压治疗药物和治
7、疗方案在长期治疗过程中对血压控制、靶器官、不良反应、代谢以及终点事件等影响的差异。,新动向(三),ARB动态血压监测研究系统综述 24h平均下降值,Fabia MJ, et al. J Hypertens. 2007;25:1327-1336,ARB动态血压监测研究系统综述 治疗后18-24h平均下降值,Fabia MJ, et al. J Hypertens. 2007;25:1327-1336,Weir MR, et al. Am J Hypertens 2007;20:807,缬沙坦剂量对降压疗效的影响 达标率和达标时间,Weir MR, et al. Am J Hypertens 20
8、07;20:807,缬沙坦不同剂量对降压疗效的影响,Reduction of proteinuria after one year of treatment: 29% with Micardis 80 vs. 20% with losartan 100, p0.05,Comparative Long term Efficacy of Two AT1 Receptor Blockers (Telmisartan vs. Losartan) on Proteinuria in Patients with Type-2 Diabetes and Overt Nephropathy and Hyper
9、tension Bakris G, et al. 22th ASH Meeting, May 21, 2007, CHICAGO,J hypertens. 2005; 23: 445-453.,NICE Combi Study (Nifedipine and Candesartan Combination),Controlled-release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension,Combination,Uptitration,NICE C
10、ombi Study Nifedipine CR & Candesartan versus High Dose Candesartan,0,0.02,-0.02,-0.04,-0.06,-0.08,-0.10,-0.12,两组间P 0.002,JMICB:长效硝苯地平与ACEI 延缓冠状动脉粥硬化进展的比较,长效硝苯地平,ACEI,治疗持续3年,治疗后冠脉管腔最小直径变化,（mm）,0.020.27 mm P 0.543,0.120.27 mm P 0.001,Shinoda E, et al. Hypertension. 2005 Jun;45(6):1153-8.,*local defin
11、ition,ONTARGET:Renal Dysfunction Dialysis & Related Death Tel + Ram vs. Ram,在心血管高危患者，常同时存在以肾小动脉硬化和缺血性损害为特点的CKD。糖尿病性和非糖尿病性肾病与慢性缺血性肾脏病在病理生理、诊断和治疗方面应当有所切割。,Antihypertensive drug treatment and the development of diabetes：Meta-analysis,ARBs多效性的差异,Uric acid excretion,PPAR gamma SNS inhibiton Anti-infl/Ant
12、iplatelet,AT1-blockade AT2-stimulation,Telmisartan, EXP 3179 Eprosartan EXP 3179,Class-Effect Balance varies Magnitude varies Depending on dose,Losartan,降压药物多效性(pleiotropic)的临床意义, 降压药物多效性的协同作用有利于降压治疗中多种心血管危险因素的综合控制，有助于保护靶器官和干预病理生理环节，从而在特定情况下可能转化为更大程度地降低心血管危险。 降压药物多效性将成为临床优化选择降压药物的重要依据和靓点。,（氨氯地平+/-培哚
13、普利 Vs. 阿替洛尔+/-苄氟噻嗪）,*P0.05,降低百分比 (%),-35,-30,-25,-20,-15,-10,-5,0,*,*,*,*,*,*,*,非致死心梗 和冠心病死亡,心血管 死亡,总死亡,总冠脉事件,致死/ 非致死性 卒中,总心血管 事件和 介入,新发 糖尿病,肾损害,Dahlof B, Sever P, et al. Lancet. 2005;366:895-906.,ASCOT-BPLA:终点事件发生率,累计事件发生率（%）,HR (95% CI): 0.80 (0.72, 0.90),(天),P = 0.0002,ACEI / HCTZ,CCB / ACEI,650,
14、526,Kenneth Jamerson, et al. Late Breaker presentation at ACC 2008.,ACCOMPLISH: 心血管复合终点,20%,ACCOMPLISH: 意义, 对特定人群选择优化的降压治疗方案提供了循证证据。 ACEI / CCB联合特别有利于减少冠心病事件(心肌梗死、不稳定性心绞痛、血运重建)。,在优化的基础上，简化降压治疗模式,寻找强效、快捷、平稳和安全的联合治疗方案和途径。,新动向(三),降压治疗模式的历史演进,序贯治疗(sequential monotherapy) 阶梯治疗(stepped-care) 联合治疗(Combinat
15、ion),Choose between,Low-dose 2-drug combination,Low-dose single agent,Not at BP goal,Full dose of single agent,Switch to different agent at low dose,Full dose of 2-drug combination,Add a third drug at low dose,Not at BP goal,23 drug combination at full dose,Full doses of 23-drug combination,Full-dos
16、e single agent,Marked BP elevation High/very high CV risk Lower BP target,Mild BP elevation Low/moderate CV risk Conventional BP target,Task Force for ESHESC. J Hypertens 2007;25:110587,Algorithm for Treatment of Hypertension(ESH/ESC),TALENT study,STudy EvALuating the Efficacy of Nifedipine GITS -Te
17、lmisartan in Blood Pressure Control,i) Nifedipine GITS 20 mg then add Telmisartan ii) Telmisartan then add Nifedipine iii) Nifedipine / Telmisartan combination,Percentage of patients fully adherent to fixed-dose Combination therapy and coadministered 2-pill therapy,100,90,80,70,60,50,40,30,20,10,0,0,3,6,9,12,15,18,21,24,27,Months after start of therapy,21%,17%,Percentage of patients fully adherent,Fixed-dose combination Coadministration of 2 pills,Sturkenboom M, et al. 15th ESH meeting, Milan, Italy, June 17-21, 2005,