新型固定剂量降压制剂安博诺理论与实践张维忠

新型固定剂量降压制剂新型固定剂量降压制剂安博诺安博诺 理论与实践理论与实践降压治疗发展的总趋势降压治疗发展的总趋势 强化强化 优化优化 简化简化 降压治疗模式的历史演进降压治疗模式的历史演进 序贯治疗序贯治疗(sequential monotherapy)阶梯治疗阶梯治疗(stepped-care)联合治疗联合治疗(Combination)不同降压机制药物联合治疗的不同降压机制药物联合治疗的降压效应降压效应疗效疗效(A+B)=(A+B)=疗效疗效(A)+(A)+疗效疗效(B)(B)疗效疗效(A+B)(A+B)疗效疗效(2A)(2A)或或 疗效疗效(2B)(2B)Trials testing two pressure lowering drugs separately and in combinationExpected fall in systolic blood pressure(mm Hg)Observed fall in systolic blood pressure(mmHg)0-10-20-30-40-40-30-20-100Law MR.BMJ 2003;326:1427不同降压机制药物联合治疗的不同降压机制药物联合治疗的不良反应不良反应不良反应不良反应(A+B)(A+B)不良反应不良反应(A)+(A)+不良反应不良反应(B)(B)不良反应不良反应(A+B)(A+B)不良反应不良反应(2A)(2A)或或 不良反应不良反应(2B)(2B)联合治疗减少或减轻不良反应的机制联合治疗减少或减轻不良反应的机制u通过不同的药理作用中和或对抗相通过不同的药理作用中和或对抗相互的不良反应互的不良反应u通过减少剂量避免不良反应。通过减少剂量避免不良反应。Choose betweenLow-dose 2-drug combinationLow-dose single agentNot at BP goalFull dose ofsingle agentSwitch todifferent agentat low doseFull dose of2-drugcombinationAdd athird drugat low doseNot at BP goal23 drugcombinationat full doseFull doses of 23-drugcombinationFull-dosesingle agentMarked BP elevationHigh/very high CV riskLower BP targetMild BP elevationLow/moderate CV riskConventional BP targetTask Force for ESHESC.J Hypertens 2007;25:110587Algorithm for Treatment of Hypertension 在多种在多种降压药物联合治疗方案中，降压药物联合治疗方案中，ARB/HCTZARB/HCTZ是一种双赢的联合方案是一种双赢的联合方案。HCTZHCTZ明显提高明显提高ARBARB的降压幅度和速度的降压幅度和速度;ARB;ARB显著显著减少和减轻减少和减轻HCTZHCTZ的不良反应。的不良反应。ARBsARBs降压疗效的荟萃分析降压疗效的荟萃分析4343项研究，项研究，1128111281例例 DBPDBP(mmHg)(mmHg)降压有效率降压有效率(%)(%)单药低剂量单药低剂量 8.2-8.9 508.2-8.9 50 单药高剂量单药高剂量 9.5-10.4 559.5-10.4 55 低剂量低剂量+HCTZ 9.9-13.6 70+HCTZ 9.9-13.6 70Conlin PR,et al.Am J Hypertens.2000;13:418Reduction 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)ARBARB抵销噻嗪类利尿剂的副作用抵销噻嗪类利尿剂的副作用血容量心输出量肾血流量PRA 体位性低血压体位性低血压GFR 肾前性氮质血症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糖耐量 LDL-C 血尿酸血尿酸 血钙血钙 ARBThiazide Diuretics,Potassium,and the Development of Diabetes:A Quantitative ReviewZillich AJ,et al.Hypertension 2006;48:219-224.在在5959个临床试验个临床试验5852058520例使用噻嗪类利尿剂的治疗过程中例使用噻嗪类利尿剂的治疗过程中,发现发现血钾与血糖改变之间存在密切的相关性血钾与血糖改变之间存在密切的相关性(r:-0.54,r:-0.54,95%CI:-0.67 95%CI:-0.67 -0.36;-0.36;p0.01p140 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 GoalSBP GoalINCLUSIVE Blood Pressure Goal Attainment at Week 18INCLUSIVE Blood Pressure Goal Attainment at Week 2,10,and 18 by Age GroupAge Group 65 years 65 yearsSBP 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 96Am J Geriatr Cardiol.2008;17:27RAPiHD Severe Study Design,Results and ConclusionsStudy DesignPrimary endpointIrbesartan150mgForce-titrate toirbesartan300mgPlacebolead-in(washout)Irbesartan/HCTZ150mg/12.5mgForce-titrate toirbesartan/HCTZ300mg/25mgRWeek 5Week 1Neutel JM et al.J Clin Hypertens 2006;8:850857*Change in SeSBP from Baseline(mmHg)*P0.0001Neutel JM et al.J Clin Hypertens 2006;8:850857Combination Therapy Achieves More Rapid Blood Pressure Reductions Compared with MonotherapySignificantly More Patients in the Combination Group Had Controlled Blood Pressure*Subjects with Controlled Blood Pressure (%)*P0.023;*P0.001Neutel JM et al.J Clin Hypertens 2006;8:850857Irbesartan Irbesartan+HCTZSimilar Low Rates of Laboratory Marker Abnormalities Observed in Both Treatment GroupsIrbesartan/HCTZ(n=468)Irbesartan(n=227)BP Goal Achevement in Patients with Uncontrolled HypertensionSchrader J,et al.Clin Drug Invest 2007;27:783-796在在日常临床实践日常临床实践中中,Irb/HCTZ治疗治疗14200例例血压未获控制血压未获控制的德国高血压患者的德国高血压患者,观察治疗观察治疗9个月时的降压疗效和不良反应。个月时的降压疗效和不良反应。Treat-to-Target:安博诺安博诺(150/12.5)降压幅度降压幅度Schrader J,et al.Clin Drug Invest 2007;27:783-796Treat-to-Target 结论结论 Irb/HCTZ能强效控制各种类型高血压，能强效控制各种类型高血压，包括代谢综合征。包括代谢综合征。Irb/HCTZ不良反应很低，仅不良反应很低，仅0.62%。Irb/HCTZ长期治疗依从性高达长期治疗依从性高达92%。