新型固定剂量降压制剂安博诺_理论与实践_张维忠.ppt
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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 (
2、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 combin
3、ation,Low-dose single agent,Not at BP goal,Full dose of single agent,Switch to different agent at low dose,Full dose of 2-drug combination,Add a third drug at low dose,Not at BP goal,23 drug combination at full dose,Full doses of 23-drug combination,Full-dose single agent,Marked BP elevation High/ve
4、ry 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
5、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),A
6、RB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:
7、-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 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。,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,Propor
8、tion of patients persistent with 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,Patient Adherence and Persistence with Antihypertensive Therapy: One- versus Two-pill Combination,Sturkenboom M, et al. 15th ESH meeting,
9、 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,Percentage of patients fully adherent to fixed-dose Combination 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%,Per
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