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1、新型固定剂量降压制剂安博诺 理论与实践,降压治疗发展的总趋势, 强化 优化 简化,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(Combination),不同降压机制药物联合治疗的降压效应,疗效(A+B) = 疗效(A) + 疗效(B),疗效(A+B) 疗效(2A) 或 疗效(2B),Trials testing two pressure lowering drugs separately and in combination,Expected fall in systolic blood pressure (
2、mm Hg),Observed fall in systolic blood pressure (mmHg),0,-10,-20,-30,-40,-40,-30,-20,-10,0,Line of identity,Law MR. BMJ 2003;326:1427,不同降压机制药物联合治疗的不良反应,不良反应(A+B) 不良反应(A) + 不良反应(B),不良反应(A+B) 不良反应(2A) 或 不良反应(2B),联合治疗减少或减轻不良反应的机制,通过不同的药理作用中和或对抗相互的不良反应 通过减少剂量避免不良反应。,Choose between,Low-dose 2-drug combin
3、ation,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-dose single agent,Marked BP elevation High/ve
4、ry 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,在多种降压药物联合治疗方案中，ARB/HCTZ是一种双赢的联合方案。HCTZ明显提高ARB的降压幅度和速度;ARB显著减少和减轻HCTZ的不良反应。,ARBs降压疗效的荟萃分析 43项研究，11281例,DBP(mmHg) 降压有效
5、率(%),单药低剂量 8.2-8.9 50,单药高剂量 9.5-10.4 55,低剂量+HCTZ 9.9-13.6 70,Conlin PR, et al. Am J Hypertens. 2000;13:418,Reduction in BP With Combination Therapy, BP (mm Hg),Weir MR et al. Am J Hypertens. 2001;14:665-671.,BNZ + 160 mg Valsartan (n = 23),HCTZ + 160 mg Valsartan (n = 30),320 mg Valsartan (n = 28),A
6、RB抵销噻嗪类利尿剂的副作用,血容量,心输出量,肾血流量,PRA ,体位性低血压,GFR ,肾前性氮质血症,肾小管尿酸和钙的重吸收,醛固酮,低血钾,糖耐量,LDL-C ,血尿酸,血钙,ARB,Thiazide Diuretics, Potassium, and the Development of Diabetes: A Quantitative Review,Zillich AJ, et al. Hypertension 2006;48:219-224.,在59个临床试验58520例使用噻嗪类利尿剂的治疗过程中, 发现血钾与血糖改变之间存在密切的相关性 (r: -0.54, 95% CI:
7、-0.67 -0.36; p0.01), 提示避免低血钾可阻止噻嗪类利尿剂导致的新发2型糖尿病。,固定剂量联合制剂通过多层次设计(Factorial Design)和效应面分析(Response surface Analyses)研究，具有合理的剂量配伍。相对于处方临时联合，固定剂量联合简化治疗药品，减少治疗费用，提高长期治疗依从性和持续性，有利于血压控制达标。,降压治疗持续性,1.0,0.8,0.6,0.4,0.2,0,0,100,200,300,400,500,600,700,800,Days after start of antihypertensive treatment,Propor
8、tion of patients persistent with treatment,Sturkenboom M, et al. 15th ESH meeting, Milan, Italy, June 17-21, 2005,8988例新诊断高血压，平均随访治疗2年， Rotterdam, The Netherlands,Patient Adherence and Persistence with Antihypertensive Therapy: One- versus Two-pill Combination,Sturkenboom M, et al. 15th ESH meeting,
9、 Milan, Italy, June 17-21, 2005,ACEI/HCTZ (n=458) vs. ACEI+HCTZ (n=297) 治疗观察2年，比较长期治疗的依从性和持续性,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%,Per
10、centage of patients fully adherent,Fixed-dose combination Coadministration of 2 pills,The INCLUSIVE Trial The Irbesartan/HCTZ Blood Pressure Reduction in Diverse Patient Population,Neutel JM, et al. J Clin Hypertens 2005;7:578-586,Minimum 4 weeks,1,005 Uncontrolled on Single Antihypertensive Agent,I
11、NCLUSIVE: Study Design,Multicenter (119 sites across the US), prospective, open-label, single-arm study,Screening,Intent-to-treat (ITT) population, n = 736. Week 18 aggregate data for irbesartan/HCTZ 150/12.5 mg and 300/25 mg include all patients whose BP was controlled from baseline. Entry criteria
12、 at screening were SBP 140 mmHg, 130 mmHg in type 2 diabetes; entry criterion at each stage of the study was DBP 70-109 mmHg; mean DBP at baseline = 91.3 mmHg. Some patients were at goal DBP at baseline. * Goal: SBP 140 mmHg, DBP 90 mmHg, except patients with type 2 diabetes: SBP 130 mmHg, DBP 80 mm
13、Hg. BP = blood pressure; DBP = diastolic blood pressure; SBP = systolic blood pressure.,DBP Goal,SBP Goal,INCLUSIVE Blood Pressure Goal Attainment at Week 18,INCLUSIVE Blood Pressure Goal Attainment at Week 2, 10, and 18 by Age Group,Age Group 65 years 65 years,SBP goal (%) At Week 2 3 4 At Week 10
14、57 52 At Week 18 79 73 DBP goal (%) At Week 2 27 63 At Week 10 65 86 At Week 18 78 96,Am J Geriatr Cardiol. 2008;17:27,RAPiHD Severe Study Design, Results and Conclusions,Study Design,Force-titrate to irbesartan 300mg,Placebo lead-in (washout),Force-titrate to irbesartan/HCTZ 300mg/25mg,R,Week 5,Wee
15、k 1,Neutel JM et al. J Clin Hypertens 2006;8:850857,*,*,*,*,Change in SeSBP from Baseline (mmHg),*P0.0001,Neutel JM et al. J Clin Hypertens 2006;8:850857,Combination Therapy Achieves More Rapid Blood Pressure Reductions Compared with Monotherapy,Significantly More Patients in the Combination Group H
16、ad Controlled Blood Pressure,*,*,*,Subjects with Controlled Blood Pressure (%),*,* P0.023; *P0.001,Neutel JM et al. J Clin Hypertens 2006;8:850857,Irbesartan,Irbesartan + HCTZ,Similar Low Rates of Laboratory Marker Abnormalities Observed in Both Treatment Groups,BP Goal Achevement in Patients with U
17、ncontrolled Hypertension,Results of the Treat-to-Target Post-Marketing Survey with Irbesartan,Schrader J, et al. Clin Drug Invest 2007;27:783-796,在日常临床实践中, Irb/HCTZ治疗14200例 血压未获控制的德国高血压患者, 观察治疗9个月时的降压疗效和不良反应。,Reductions in diastolic BP (DBP) and systolic BP (SBP) compared with baseline at 3 and 9 mo
18、nths in patients with mild, moderate or severe hypertension treated with a fixed combination of irbesartan 150mg /HCTZ 12.5mg once daily as first-line combination therapy,Treat-to-Target:安博诺(150/12.5)降压幅度,Schrader J, et al. Clin Drug Invest 2007;27:783-796,Treat-to-Target 结论, Irb/HCTZ能强效控制各种类型高血压， 包括代谢综合征。 Irb/HCTZ不良反应很低，仅0.62%。 Irb/HCTZ长期治疗依从性高达92%。,