降壓治療研究新動向

1、降壓治療研究新動向強化、優(yōu)化和簡化,擴展降壓治療能獲益的人群，當前主要聚焦在80歲以上高齡高血壓患者和血壓水平<140/90的心血管高?；颊?心、腦血管病與糖尿病)。,新動向(一),The results of this trial should provide reliable evidence about the effects of blood-pressure-lowering therapy in this very

2、 high-risk population.,安慰劑,納催離緩釋片± 雅施達安慰劑,HYVET: 總死亡率,總死亡率降低21%,隨訪時間（年）,百分率%,納催離緩釋片±雅施達,19121933,14921565,814877,379420,202231,從HYVET到臨床實踐,■ 適用于收縮壓160mmHg以上，一般狀況尚好，生活能自理，認知功能無明顯減退的高齡高血壓患者?！?降壓速度應該相對

3、較平緩，避免體位性低血壓。血壓控制目標值150/80mmHg。,,RAS阻滯劑治療心血管高危患者循證證據(jù),HOPE (Ramipril,2000)PROGRESS (Perindopril, 2001)EUROPA (Perindopril, 2003)ADVANCE (Perin/Indap, 2007)ONTARGET (Telmisartan, 2008),HOPE 139/79

4、 3/3PROGRESS 147/86 9/4EUROPA 137/82 5/2ADVANCE 145/81 5/3ONTARGET 142/82 6/4,,,基線血壓 血壓↓,RAS阻滯劑治療心血管高危患者基線血壓與血壓下降幅度,,mmHg,HT,NT,S,D,159.0,159.0,94.0,91.0,136.0

5、,127.2,79.0,74.8,Blood Pressure values in PROGRESS,在心血管高?；颊? 強化血壓控制。血壓控制目標值<130/80mmHg正在不斷獲得循證證據(jù)。,新動向(二),SBP,From UKPDS to ADVANCE,ACCORD StudyAction to Control Cardiovascular risk in Diabetes,Prisant LM. J Clin Phar

6、macol 2004; 44(4):423-430,● HbA1c: ≤6.0% vs 7.0-7.9% (因強化治療總死亡率增加,08年2月7日宣布提前中止)● SBP: ≤120 mmHg vs ≤140 mmHg,Arima H, et al. J Hypertens. 2006;24:1201-1208,PROGRESS:,,,,,,,,,,,,,,,100,80,60,40,20,0,<120

7、,120-139,140-159,?60,,,,,,,,,,,,,100,80,60,40,20,0,<70,70-79,80-89,?90,Achieved systolic blood pressure levels(mmHg),Achieved systolic blood pressure levels(mmHg),Age-and sex-adjusted incidence rate,CKD: P trend=0.0

8、04Non-CKD: P trend<0.0001,CKD: P trend=0.001Non-CKD: P trend<0.0001,CKDNon-CKD,Incidence rate (1000 person-years),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,PROGRESS CKD Substudy: SBP and CVD,Messerli FH, et al. Ann

9、Intern Med. 2006;144:884-893,冠心病患者血壓控制水平與心血管危險,Rosendorff C, et al. Circulation 2007;115:,Treatment of Hypertension in IHDA Scientific Statement from AHA, 2007.4,● 冠心病患者需要積極控制血壓，合理的血壓控 制目標值<130/80mmHg。（Ⅱa,B）

10、● 應該相對緩慢降低血壓，避免DBP<60mmHg。,優(yōu)化降壓治療方案，比較不同降壓治療藥物和治療方案在長期治療過程中對血壓控制、靶器官、不良反應、代謝以及終點事件等影響的差異。,新動向(三),ARB動態(tài)血壓監(jiān)測研究系統(tǒng)綜述24h平均下降值,Fabia MJ, et al. J Hypertens. 2007;25:1327-1336,ARB動態(tài)血壓監(jiān)測研究系統(tǒng)綜述治療后18-24h平均下降值,Fabia MJ, et al.

11、 J Hypertens. 2007;25:1327-1336,Weir MR, et al. Am J Hypertens 2007;20:807,纈沙坦劑量對降壓療效的影響達標率和達標時間,Weir MR, et al. Am J Hypertens 2007;20:807,纈沙坦不同劑量對降壓療效的影響,Reduction of proteinuria after one year of treatment:29% with

12、Micardis 80 vs. 20% with losartan 100, p<0.05,Comparative Long term Efficacy of Two AT1 Receptor Blockers (Telmisartan vs. Losartan) on Proteinuria in Patients with Type-2 Diabetes and Overt Nephropathy and Hyperten

13、sionBakris G, et al. 22th ASH Meeting, May 21, 2007, CHICAGO,J hypertens. 2005; 23: 445-453.,NICE Combi Study(Nifedipine and Candesartan Combination),Controlled-release nifedipine and candesartan low-dose combinati

14、on therapy in patients with essential hypertension,Combination,Uptitration,NICE Combi Study Nifedipine CR & Candesartan versus High Dose Candesartan,,,,0,0.02,,,,,,,-0.02,-0.04,-0.06,-0.08,-0

15、.10,-0.12,,,,兩組間P ＝0.002,JMIC－B:長效硝苯地平與ACEI延緩冠狀動脈粥硬化進展的比較,,,長效硝苯地平,ACEI,治療持續(xù)3年,治療后冠脈管腔最小直徑變化,（mm）,0.02±0.27 mmP ＝0.543,－0.12±0.27 mmP <0.001,Shinoda E, et al. Hypertension. 2005 Jun;45(6):1153-8.,*local

16、definition,ONTARGET:Renal Dysfunction Dialysis & Related DeathTel + Ram vs. Ram,在心血管高?；颊?，常同時存在以腎小動脈硬化和缺血性損害為特點的CKD。糖尿病性和非糖尿病性腎病與慢性缺血性腎臟病在病理生理、診斷和治療方面應當有所切割。,Antihypertensive drug treatment and the development of di

17、abetes：Meta-analysis,ARBs多效性的差異,Uric acid excretion,PPAR gammaSNS inhibitonAnti-infl/Antiplatelet,AT1-blockadeAT2-stimulation,Telmisartan, EXP 3179 EprosartanEXP 3179,Class-EffectBalance varies? Magnitude varies

18、Depending on dose,,Losartan,降壓藥物多效性(pleiotropic)的臨床意義,● 降壓藥物多效性的協(xié)同作用有利于降壓治療中多種心血管危險因素的綜合控制，有助于保護靶器官和干預病理生理環(huán)節(jié)，從而在特定情況下可能轉化為更大程度地降低心血管危險?！?降壓藥物多效性將成為臨床優(yōu)化選擇降壓藥物的重要依據(jù)和靚點。,（氨氯地平+/-培哚普利 Vs. 阿替洛爾+/-芐氟噻嗪）,*P<0.05,降低百分比(%),,

19、,,,,,,,,,,,,,,,,,-35,-30,-25,-20,-15,-10,-5,0,*,*,*,*,*,*,*,非致死心梗和冠心病死亡,心血管死亡,總死亡,總冠脈事件,致死/非致死性卒中,總心血管事件和介入,新發(fā)糖尿病,腎損害,Dahlof B, Sever P, et al. Lancet. 2005;366:895-906.,ASCOT-BPLA:終點事件發(fā)生率,累計事件發(fā)生率（%）,HR (95% CI):

20、0.80 (0.72, 0.90),,(天),P = 0.0002,ACEI / HCTZ,CCB / ACEI,650,526,Kenneth Jamerson, et al. Late Breaker presentation at ACC 2008.,ACCOMPLISH: 心血管復合終點,20%,ACCOMPLISH: 意義,■ 對特定人群選擇優(yōu)化的降壓治療方案提供了循證證據(jù)?！?ACEI / CCB聯(lián)合特別有利于

21、減少冠心病事件(心肌梗死、不穩(wěn)定性心絞痛、血運重建)。,在優(yōu)化的基礎上，簡化降壓治療模式,尋找強效、快捷、平穩(wěn)和安全的聯(lián)合治療方案和途徑。,新動向(三),降壓治療模式的歷史演進,序貫治療(sequential monotherapy) 階梯治療(stepped-care) 聯(lián)合治療(Combination),,,,,Choose between,Low-dose 2-drug combination,Low-dose sing

22、le 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,2–3 drugcombinationat full dose,Full doses of 2–3-drug

23、combination,Full-dosesingle agent,Marked BP elevationHigh/very high CV riskLower BP target,Mild BP elevationLow/moderate CV riskConventional BP target,Task Force for ESH–ESC. J Hypertens 2007;25:1105–87,,,,,,,Algor

24、ithm for Treatment of Hypertension(ESH/ESC),TALENT study,STudy EvALuating the Efficacy of Nifedipine GITS -Telmisartan in Blood Pressure Control,i) Nifedipine GITS 20 mg … then add Telmisartan ii) Tel

25、misartan … then add Nifedipine iii) Nifedipine / Telmisartan combination,Percentage of patients fully adherent to fixed-doseCombination therapy and coadministered 2-pill therapy,,,,,,,,,,,,,,,,,,,,,

26、,,,,,,,,,,,,,,,,,,,,,,,,,,,,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%,Percentage of patients fully adherent,Fixed-dose combinationCoadministration of 2 pills,Sturke