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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(mm Hg),Obse
2、rved 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 combination,Low-dose sing
3、le agent,Not at BP goal,Full dose ofsingle agent,Switch todifferent agentat low dose,Full dose of2-drugcombination,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,
4、Mild BP elevationLow/moderate CV riskConventional 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)降压有效率(%),单药低剂量 8.2-8.9 50,单药高剂量 9.5-10.4
5、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 mgValsartan(n=23),HCTZ+160 mgValsartan(n=30),320 mgValsartan(n=28),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,体位性低血压,GFR,肾前性氮质血症,肾小管尿酸和钙的
6、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:-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 De
7、sign)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,Proportion of patients persistentwith treatment,Sturkenboom M,et al.15th ESH meetin
8、g,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,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,Perce
9、ntage of patients fully adherent to fixed-doseCombination 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 combinationCoadministration of 2 pills,The INCLUSIVE T
10、rialThe Irbesartan/HCTZ Blood Pressure Reduction in Diverse Patient Population,Neutel JM,et al.J Clin Hypertens 2005;7:578-586,Minimum4 weeks,1,005 Uncontrolledon SingleAntihypertensiveAgent,INCLUSIVE:Study Design,Multicenter(119 sites across the US),prospective,open-label,single-arm study,Screening
11、,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;entry criterion at each stage of the study was DBP 70-109 mm
12、Hg;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=systolic blood pressure.,DBP Goal,SBP Goal,INCLUSIVE Blood Pressure Goal Attain
13、ment 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 57 52 At Week 18 79 73DBP 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,Resu
14、lts and Conclusions,Study Design,Force-titrate toirbesartan300mg,Placebolead-in(washout),Force-titrate toirbesartan/HCTZ300mg/25mg,R,Week 5,Week 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,Combin
15、ation Therapy Achieves More Rapid Blood Pressure Reductions Compared with Monotherapy,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,Irbesa
16、rtan+HCTZ,Similar Low Rates of Laboratory Marker Abnormalities Observed in Both Treatment Groups,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142
17、00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 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,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%。,
