新型固定剂量降压制剂安博诺 理论与实践 张维忠课件.ppt

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1、新型固定剂量降压制剂安博诺理论与实践,新型固定剂量降压制剂安博诺,降压治疗发展的总趋势, 强化 优化 简化,降压治疗发展的总趋势 强化,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),降压治疗模式的历史演进 序贯治疗(sequential,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),不同降压机制药物联合治疗的降压效应疗效(A+B) = 疗效(,Trials testing two pressure l

2、owering drugs separately and in combination,Expected fall in systolic blood pressure (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,Trials testing two pressure lo,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

3、应(A+B) 不良反应(2A) 或 不良反应(2B),不同降压机制药物联合治疗的不良反应不良反应(A+B) 不,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。,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,Choose between,Low-dose 2-drug combination,Low-dose single agent,Not at BP goal,Full dose ofsingle agent,Switch todifferent agentat low dose,Full dose of2-drugco

4、mbination,Add athird drugat low dose,Not at BP goal,23 drugcombinationat full dose,Full doses of 23-drugcombination,Full-dosesingle agent,Marked BP elevationHigh/very high CV riskLower BP target,Mild BP elevationLow/moderate CV riskConventional BP target,Task Force for ESHESC. J Hypertens 2007;25:11

5、0587,Algorithm for Treatment of Hypertension,Choose betweenLow-dose 2-drug,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。,在多种降压药物联合治疗方案中，ARB/HCTZ是,ARBs降压疗效的荟萃分析43项研究，11281例,DBP(mmHg) 降压有效率(%),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 H

6、ypertens. 2000;13:418,ARBs降压疗效的荟萃分析 DBP(mmHg) 降压有,Reduction in BP With Combination Therapy, BP (mm Hg),Weir MR et al. Am J Hypertens. 2001;14:665-671.,BNZ + 160 mgValsartan(n = 23),HCTZ + 160 mgValsartan(n = 30),320 mgValsartan(n = 28),Reduction in BP With Combinati,ARB抵销噻嗪类利尿剂的副作用,血容量,心输出量,肾血流量,PRA

7、 ,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,ARB抵销噻嗪类利尿剂的副作用血容量心输出量肾血流量P,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: -0.67

8、-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。,Thiazide Diuretics, Potassium,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。,固定剂量联合制剂通过多层次设计(Fac,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 afte

9、r start of antihypertensive treatment,Proportion of patients persistentwith 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,降压治疗持续性1.00.80.60.40.200100200,Patient Adherence and Persistence with Antihypertensive Therapy:

10、One- versus Two-pill Combination,Sturkenboom M, et al. 15th ESH meeting, 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,Patient Adherence and Persiste,Percentage of patients fully adherent to fixed-doseCombination therapy and coadministered 2-pill therap

11、y,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 combinationCoadministration of 2 pills,Percentage of patients fully a,新型固定剂量降压制剂安博诺_理论与实践_张维忠课件,新型固定剂量降压制剂安博诺_理论与实践_张维忠课件,The INCLUSIVE TrialThe Irbesar

12、tan/HCTZ Blood Pressure Reduction in Diverse Patient Population,Neutel JM, et al. J Clin Hypertens 2005;7:578-586,The INCLUSIVE TrialNeutel JM,Minimum4 weeks,1,005 Uncontrolledon SingleAntihypertensiveAgent,INCLUSIVE: Study Design,Multicenter (119 sites across the US), prospective, open-label, singl

13、e-arm study,Screening,Minimum4 weeks1,005 Uncontrol,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 at screening were SBP 140 mmHg, 130 mmHg in type 2 diabetes; en

14、try 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 mmHg.BP = blood pressure; DBP = diastolic blood pressure; SBP = sys

15、tolic blood pressure.,DBP Goal,SBP Goal,INCLUSIVE Blood Pressure Goal Attainment at Week 18,Intent-to-treat (ITT) populati,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 57 52 At Week 18 79 73DBP goal (%)

16、At Week 2 27 63 At Week 10 65 86 At Week 18 78 96,Am J Geriatr Cardiol. 2008;17:27,INCLUSIVE Blood Pressure Goal,RAPiHD Severe Study Design, Results and Conclusions,RAPiHD Severe Study,Study Design,Force-titrate toirbesartan300mg,Placebolead-in(washout),Force-titrate toirbesartan/HCTZ300mg/25mg,R,We

17、ek 5,Week 1,Neutel JM et al. J Clin Hypertens 2006;8:850857,Study DesignPrimary endpointIr,*,*,*,*,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,*Change in SeSB

18、P from Base,Significantly More Patients in the Combination Group Had 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,Significantly More Patients in,Similar Low Rates of Labora

19、tory Marker Abnormalities Observed in Both Treatment Groups,Similar Low Rates of Laborator,BP Goal Achevement in Patients with Uncontrolled 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

20、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。,BP Goal Achevement in Patients,Reductions in diastolic BP (DBP) and systolic BP (SBP) compared with baseline at 3 and 9 months 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,Reductions in diastolic BP (DB,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%。,Treat-to-Target 结论 Irb/HCTZ能,