新型固定剂量降压制剂安博诺_理论与实践课件

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,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,(,s,equential,monotherapy,),阶梯治疗,(,s,tepped-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),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 combination,Low-dose single 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 drugcombination,at full dose,Full doses of 2,3-drug,combination,Full-dosesingle 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,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 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),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;,p140 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 mmHg.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 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,Primary endpoint,Irbesartan,150mg,Force-titrate to,irbesartan,300mg,Placebo,lead-in,(washout),Irbesartan/HCTZ,150mg/12.5mg,Force-titrate to,irbesartan/HCTZ,300mg/25mg,R,Week 5,Week 1,Neutel,JM,et al,.,J Clin,Hypertens,2006;8:850,857,*,*,*,*,Change in,SeSBP,from,Baseline (mmHg),*,P0.0001,Neutel,JM,et al,.,J Clin,Hypertens,2006;8:850,857,Combination 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;8:850,857,Irbesartan,Irbesartan,+,HCTZ,Similar Low Rates of Laboratory Marker Abnormalities Observed in Both Treatment Groups,Irbesartan/HCTZ,(n=468),Irbesartan,(n=227),Elevated,creatinine,3.0,1.8,Elevated,LFTs,0.2,0,High potassium,0.6,1.3,Low potassium,0,0,High glucose,0.9,0,High cholesterol,0,0,High uric acid,0.2,0,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,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,0,-10,-20,-30,-40,-50,-60,-70,0,-10,-20,-30,-40,-50,-60,-70,0,-10,-20,-30,-40,-50,-60,-70,Mild hypertension,(SBP 140-159 or DBP 90-99mm Hg),Moderate hypertension,(SBP 160-179 or DBP 99-109mm Hg),Severe hypertension,(SBP,180,or DBP,110mm Hg),Diastolic,Systolic,Diastolic,Systolic,Diastolic,Systolic,3 months,9 months,BP reduction (mm Hg),-6.1,-9.8,-15.6,-20.2,-11.7,-14.1,-23.7,-29,-13.3,-18.5,-46.7,-60.5,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,I,rb,/HCTZ,能强效控制各种类型高血压，,包括代谢综合征。,I,rb,/HCTZ,不良反应很低，仅,0.62%,。,Irb,/HCTZ,长期治疗依从性高达,92%,。,