新型固定劑量降壓制劑安博諾理論與實踐張維忠課件

1、新型固定劑量降壓制劑新型固定劑量降壓制劑 理論與實踐理論與實踐降壓治療發(fā)展的總趨勢降壓治療發(fā)展的總趨勢 強化強化 優(yōu)化優(yōu)化 簡化簡化 降壓治療模式的歷史演進(jìn)降壓治療模式的歷史演進(jìn) 序貫治療序貫治療( (sequential monotherapy) 階梯治療階梯治療( (stepped-care) 聯(lián)合治療聯(lián)合治療( (Combination)不同降壓機(jī)制藥物聯(lián)合治療的不同降壓機(jī)制藥物聯(lián)合治療的降壓效應(yīng)降壓效應(yīng)療效療效(A+B) = (A+B) = 療效療效(A) + (A) + 療效療效(B)(B)療效療效(A+B) (A+B) 療效療效(2A) (2A) 或或 療效療效(2B) (2B)

2、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不同降壓機(jī)制藥物聯(lián)合治療的不同降壓機(jī)制藥物聯(lián)合治療的不良反應(yīng)不良反應(yīng)不良反應(yīng)不良反應(yīng)(A+B) (A+B) 不良反應(yīng)不良反應(yīng)(A) + (A) + 不良反應(yīng)不良反應(yīng)

3、(B)(B)不良反應(yīng)不良反應(yīng)(A+B) (A+B) 不良反應(yīng)不良反應(yīng)(2A) (2A) 或或 不良反應(yīng)不良反應(yīng)(2B) (2B) 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 doseF

4、ull 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 HypertensionARBsARBs降壓療效的薈萃分析降壓療效的薈萃分析4343項研究，項研究，1128111

5、281例例 DBPDBP (mmHg) (mmHg) 降壓有效率降壓有效率(%)(%) 單藥低劑量單藥低劑量 8.2-8.9 508.2-8.9 50 單藥高劑量單藥高劑量 9.5-10.4 559.5-10.4 55 低劑量低劑量+HCTZ 9.9-13.6 70+HCTZ 9.9-13.6 70Conlin PR, et al. Am J Hypertens. 2000;13:418 BP (mm Hg)Weir MR et al. Am J Hypertens. 2001;14:665-671.BNZ + 160 mgValsartan(n = 23)HCTZ + 160 mgValsa

6、rtan(n = 30)320 mgValsartan(n = 28)血容量心輸出量腎血流量PRA 體位性低血壓體位性低血壓GFR 腎前性氮質(zhì)血癥腎前性氮質(zhì)血癥腎小管尿酸和鈣的重吸收醛固酮低血鉀糖耐量糖耐量 LDL-C 血尿酸血尿酸 血鈣血鈣 ARB在在5959個臨床試驗個臨床試驗5852058520例使用噻嗪類利尿劑的治療過程中例使用噻嗪類利尿劑的治療過程中, ,發(fā)現(xiàn)發(fā)現(xiàn)血鉀與血糖改變之間存在密切的相關(guān)性血鉀與血糖改變之間存在密切的相關(guān)性( (r: -0.54,r: -0.54, 95% CI: -0.67 95% CI: -0.67 -0.36; -0.36; p0.01p140 mmHg

7、, 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 = di

8、astolic blood pressure; SBP = systolic blood pressure.DBP GoalSBP GoalINCLUSIVE Blood Pressure Goal Attainment at Week 18Age 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:

9、27Primary endpointIrbesartan150mgForce-titrate toirbesartan300mgPlacebolead-in(washout)Irbesartan/HCTZ150mg/12.5mgForce-titrate toirbesartan/HCTZ300mg/25mgRWeek 5Week 1*Change in SeSBP from Baseline (mmHg)*P0.0001*Subjects with Controlled Blood Pressure (%)* P0.023; *P0.001Irbesartan Irbesartan + HCTZSchrader J, et al. Clin Drug Invest 2007;27:783-796在在日常臨床實踐日常臨床實踐中中, Irb/HCTZ治療治療14200例例血壓未獲控制血壓未獲控制的德國高血壓患者的德國高血壓患者, 觀察治療觀察治療9個月時的降壓療效和不良反應(yīng)。個月時的降壓療效和不良反應(yīng)。Treat-to-Target: :安博諾安博諾(150/12.5)降壓幅度降壓幅度Schrader J, et al. Clin Drug In