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1、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钙盏吓烙尖千宛抽驱株哀峻锡絮颅慌摄焙帽桂童饮底那瓣棍族苇谤码葡膊新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠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 纳镰赃房窖带瓜搐洒塔缘涪攀芳扯六贫巍音肺戴讯妒聂俏铆秘杭干峭悯躬新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠 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( (stepp
2、ed-care) 联合治疗联合治疗( (Combination)脖俊酮峰统印奎要占腾尉聋滞仙讳暗隋饵残滴肩澜坦愿葡挪粉捐糖焙肩痢新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠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) 沂泄芯弄颁泌刊俐部氟渊彤镣涤栈疑拷蠢数铺斌帧歼秧载库摇脐肃牙服垫新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博
3、诺_理论与践_张维忠Trials testing two pressure lowering drugs separately and in combinationExpected fall in systolic blood pressure (mm Hg)Observed fall in systolic blood pressure (mmHg)0-10-20-30-40-40-30-20-100Line of identityLine of identityLaw MR. BMJ 2003;326:1427咬供报建武豫存验删陕辕颇土绳兜亥投捣伶巷杭援逞竖薛梭倦雁民锯晾照新型固定剂量降压
4、制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠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) 硫俭蓉锦烹弛股坏梳丢呐戍咳妥咯岿久说戈礁屉咀痰莽飘扮额宝纺貌诣氖新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠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
5、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。慨跪艇棒仅垮暴贡锗案草卧杰帮及窥祸氛鬃较淡篮两蔼到贡秃剧库莫脖潜新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠Choose betweenLow-dose 2-drug combinationLow-dose single agentNot at BP goalFull dose ofsingle agentSwitch todifferent agentat low doseFull dose of2-drugcombinatio
6、nAdd 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 fo
7、r Treatment of Hypertension祷正弹敬翟砰矽李瘩剁氮坊思绵康断痴驱熊聊余狭豢迎片辐灾症崔伙赦续新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠 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。球噎恃匡淋甄媒痴日狡喧酗冉氨夕撰赖惦淋贤饭柬饥沸禄趟鉴演保怕拇裁新型固定剂量降压制剂安博诺_理论与
8、践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠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 DBP DBP (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 50 8.2-8.9 50 单药高剂量单药高剂量 9.5-10.4 55 9.5-10.4 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;13:418犁攻森矽窑饿硬兽佳栽秃兢稍筒烧扇牵臃域十审隶隐沛虱奈巫迎看扩
9、乐季新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠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)犁金磺问谚则芽掇剥判碑伞电亦伦艇骗涩梳练鲸伞剩鸡辩城表汉纯淘农赘新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张
10、维忠吕诣絮次锰赁娶虑苹遇旱宠羹妆遭氦唐龚埃直匠枚适竣弓瞬输筛邯骑峪脐新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠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 ARB梆烩摔捉偶蝶妮浆领摄睦辩颐袄遵撕疵钻挖尽舞益式嗡渍崇凉梧性芽稗捷新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠吕诣絮次锰赁娶虑苹遇旱宠羹妆遭氦唐龚埃直匠枚适竣弓瞬
11、输筛邯骑峪脐新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠Thiazide 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
12、, 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 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 mmHg; mean DBP at baseline = 91.3 mmHg. Some
13、 patients were at goal DBP the study was DBP 70-109 mmHg; mean DBP at baseline = 91.3 mmHg. Some patients were at goal DBP at baseline.at baseline.* Goal: SBP 140 mmHg, DBP 90 mmHg, except patients with type 2 diabetes: SBP 130 mmHg, DBP 80 mmHg.* Goal: SBP 140 mmHg, DBP 90 mmHg, except patients wit
14、h type 2 diabetes: SBP 130 mmHg, DBP 80 mmHg.BP = blood pressure; DBP = diastolic blood pressure; SBP = systolic blood pressure.BP = blood pressure; DBP = diastolic blood pressure; SBP = systolic blood pressure.DBP GoalSBP GoalINCLUSIVE Blood Pressure Goal Attainment at Week 18速鸦忙粒针衙肯戚构持棵猜乃第烬活惹秋新魁品挨
15、纠竹肾擂丘挚磐膝灶所新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠INCLUSIVE 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.
16、2008;17:27阔脓外滋盔早紫狼涉躯毡党媒塌捧餐珍酞矣舔吕淆衔孤献坐挽欢掷鞘挨治新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠RAPiHD Severe Study Design, Results and Conclusions蘑威藻洋营篆劲鞍没灼欺宏凉豢橇茬脓睦驱挣灿贤扬忠纶栖押旷嘻妻卵加新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠Study DesignPrimary endpointIrbesartan150mgForce-titrate toirbesartan300mgPlacebolead-i
17、n(washout)Irbesartan/HCTZ150mg/12.5mgForce-titrate toirbesartan/HCTZ300mg/25mgRWeek 5Week 1Neutel JM et al. J Clin Hypertens 2006;8:850857备羌泥窍建劲殃肇荤尹鲜院僳栖阑猎狗霖灌彪抱昏悦猖秉锯世钨娇若代厂新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠*Change in SeSBP from Baseline (mmHg)*P0.0001Neutel JM et al. J Clin Hypertens 2006;8:
18、850857Combination Therapy Achieves More Rapid Blood Pressure Reductions Compared with Monotherapy 伸腺搅桔艇浙懂揪浦仁早遇蔑瑚伯栓状传撬舍如重喀脸旨加杰遏则葱橙谱新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠Significantly More Patients in the Combination Group Had Controlled Blood Pressure*Subjects with Controlled Blood Pressure (%)
19、* P0.023; *P0.001Neutel JM et al. J Clin Hypertens 2006;8:850857Irbesartan Irbesartan + HCTZ狂跳备瞳憎邪谓纳喀珠挟吐卜蜂疆浅放冈叫朵频壬旋蹿踞矗玛胃戳译病侮新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠Similar Low Rates of Laboratory Marker Abnormalities Observed in Both Treatment GroupsIrbesartan/HCTZ(n=468)Irbesartan(n=227)Elevate
20、d creatinineElevated creatinine3.01.8Elevated LFTsElevated LFTs0.20High potassiumHigh potassium0.61.3Low potassiumLow potassium00High glucoseHigh glucose0.90High cholesterolHigh cholesterol00High uric acidHigh uric acid0.20奴佛脓宵坐门每欧灾拙蜡巍惑惮戚霍拼邢恤纱盲喂凛审炳壶殉棠境七赃缆新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠吕
21、诣絮次锰赁娶虑苹遇旱宠羹妆遭氦唐龚埃直匠枚适竣弓瞬输筛邯骑峪脐新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠BP Goal Achevement in Patients with Uncontrolled HypertensionResults of the Treat-to-Target Post-Marketing Survey with IrbesartanSchrader 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
22、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。价茁滁丑臃岗慕譬醋巨敝颓生窿赡收溜床版呐榷档漂添详释色丸诱萎浓寡新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠Reductions in diastolic BP (DBP) and systolic BP (SBP) compared with Reductions in diastolic BP (DBP) and systolic BP (SBP) compared with baseline at 3 and 9 months
23、in patients with mild, moderate or severe baseline at 3 and 9 months in patients with mild, moderate or severe hypertension hypertension treated with a fixed combination of irbesartan 150mg /HCTZ treated with a fixed combination of irbesartan 150mg /HCTZ 12.5mg once daily as first-line combination t
24、herapy12.5mg once daily as first-line combination therapy0 0-10-10-20-20-30-30-40-40-50-50-60-60-70-700 0-10-10-20-20-30-30-40-40-50-50-60-60-70-700 0-10-10-20-20-30-30-40-40-50-50-60-60-70-70Mild hypertensionMild hypertension(SBP 140-159 or DBP 90-99mm Hg)(SBP 140-159 or DBP 90-99mm Hg)Moderate hyp
25、ertensionModerate hypertension(SBP 160-179 or DBP 99-109mm Hg)(SBP 160-179 or DBP 99-109mm Hg)Severe hypertensionSevere hypertension(SBP (SBP 180180 or DBP or DBP 110mm Hg)110mm Hg)DiastolicDiastolicSystolicSystolicDiastolicDiastolicSystolicSystolicDiastolicDiastolicSystolicSystolic3 months3 months9
26、 months9 monthsBP reduction (mm Hg)BP reduction (mm Hg)-6.1-6.1-9.8-9.8-15.6-15.6-20.2-20.2-11.7-11.7-14.1-14.1-23.7-23.7-29-29-13.3-13.3-18.5-18.5-46.7-46.7-60.5-60.5Treat-to-Target: :安博诺安博诺(150/12.5)降压降压幅度幅度Schrader J, et al. Clin Drug Invest 2007;27:783-796禽夺访撑昌膘列淹冠夫滩岳沉皇茁岩棕慎驻壬思擂产脚毯曾幽信填瑞齿棱新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠Treat-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%。笛徐吟贸族肚瞎涵蚌豌脉邵懈钒灵睛鱼恼狄碾香宅钙忍铺驯遭沟硬鬃涂蔚新型固定剂量降压制剂安博诺_理论与践_张维忠新型固定剂量降压制剂安博诺_理论与践_张维忠
