新型固定劑量降壓制劑arbhctz臨床應用中國專家共識

1、新型固定劑量降壓制劑ARB/HCTZ臨床應用的中國專家共識,北京大學人民醫(yī)院 孫寧玲,我們面臨的巨大挑戰(zhàn)：三高三低94%高血壓患者血壓不達標!,2004年《中國居民營養(yǎng)與健康狀況調(diào)查報告》,三高,三低,,,,,,,,,,,,,,0,5,10,15,20,25,30,35,知曉率,治療率,控制率,百分比（％）,30.2％,,24.7 ％,,6.1 ％,,,,薈萃分析61項回顧性觀察研究涵蓋1百萬人（40-89歲）,控制心血管危險

2、降壓是關鍵,Lewington et al. Lancet. 2002;360:1903–1913,利尿劑治療高血壓的作用1、 利尿劑減輕體內(nèi)鈉負荷，減少鈉在阻力動脈管壁中的含量，降低血管收縮的反應性。2、能增強其它降壓藥物的降壓效應，增加血管順應性。3、能夠減輕左心室肥厚4、可弱化對低鹽飲食的限制,幾項主要使用利尿劑的高血壓治療研究,1. EWPHE. Lancet. 1985; 1: 1349-1354 2.

3、STOP. Lancet. 1991; 338: 1281-1285 3. SHEP. JAMA. 1991; 265: 3255-3264,,,,,,,EWPHE,,,,,,STOP,,,,,SHEP,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,病例數(shù),,,,,,,840,,,,,,,1627,,,,,,4736,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

4、,,隨訪（年）,,,,,,,12,,,,,,,4,,,,,,4.5,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,收縮壓,,,,,,,>160,,,,,,,>180,,,,,,>160,,,,,,,,,,,,,,,-,36,,,,,,,-,47,,,,,,-,36,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,心性事件減少（,%,）,,,,,,,-,32,,,,,,,-,40,,,,

5、,,-,32,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,平均年齡,,,SBP Response to 2-Drug Combinations That Include or Do Not Include a Diuretic,With HCTZ,Without HCTZ,SBP <140 mmHg, %,,P=0.002,,,Materson, et

6、al. J Human Hypertens. 1995;9:791-795.,,,,,,,,,,,,,,,77,46,0,20,40,60,80,100,2007年ESC/ESH降壓藥物的選擇,降壓治療的主要獲益源自降低血壓本身。五大類降壓藥物：噻嗪類利尿劑鈣拮抗劑血管緊張素轉(zhuǎn)換酶 (ACE) 抑制劑血管緊張素受體阻滯劑 (ARB) ?-阻滯劑,,Myocardial infarction,Heart failure,End

7、-stage heart disease,Plaque rupture,Risk factors,,HypertensionHyperlipidemiaDiabetes,Atherosclerosis,Endothelial dysfunction,Coronary arterydisease,Dilatation/Remodeling,,,,,,,,,,,,,,,,,,Angiotensin II,The cardiovascu

8、lar continuum,Potential effects of AT1-receptor blockade,,,,,ANG II,,ANG II,,ANG II,,ANG II,,,,ARB,,,AT1,AT2,,,,,,,ANG II,,,,Vasodilation??Pathological GrowthApoptosis,,,,,,,VasodilationPathological growthApoptosisS

9、odium & water retentionNeurohumoral activationReactive oxygen speciesPro-inflammatory processes,,,,,,,,,,厄貝沙坦: 劑量反應和耐受性,安慰劑對照試驗匯總結(jié)果。*谷值坐位舒張壓 < 90 mm Hg 或從基線下降≥10 mm Hg。Man in抰 Veld AJ. J Hypertens. 1997;15(s

10、uppl 7):S27-S33.,總的治療反應率*%,,,,,,,,,,,,,,,,,(n=539),(n=277),(n=357),(n=216),厄貝沙坦 (mg/天),扣除安慰劑作用的不良反應(% 病例數(shù)),,,,,,,,,,,,,,,,,,,,(n=641),(n=297),(n=516),(n=282),,Low-does Polypill vs Standard-dose Monotherapy:Effect on

11、Systolic BP,N=108 with hypertension,drug naive; 4-week treatment,Mahmud A. Feely J. Hypertension 2007:49;272-5.,,,0,-5,-10,-15,-20,-25,-30,Comb(n=22),Capt 100mg(n=22),Amlo 5mg(n=20),Aten 50mg(n=20),Bend 2.5mg(n=22),

12、P<0.01vs monotherapies,SBP(mmHg),,單藥治療控制率低，多數(shù)使用聯(lián)合治療,“超過2/3的高血壓病人需要兩種或兩種以上不同類別的藥物而不是只用一個藥物來有效控制血壓” JNC 7,“血壓控制在140/90mmHg以內(nèi)的病人中的60％使用了兩種或兩種以上的藥物，只有30％的病人使用了一種藥物?！?ALLHAT 研究,“隨機臨床試驗證明，大多數(shù)高血壓病人為控制血壓須用兩種或兩種以上降壓藥” 中國

13、高血壓防治指南（2005修訂版）,選擇藥物組合有差別,ARB加小劑量利尿劑持續(xù)用藥比例最高，放棄治療或轉(zhuǎn)藥比例最低,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,100,90,80,70,60,50,40,30,20,10,0,0,3,6,9,12,15,18,21,24,27,自治療開始的時間（月）,21%,17%,患者比率（%）,固定復方制劑2片藥物同時服用,固定復方制劑較2片藥

14、物同服依從性高,復方固定復方制劑在指南中被推薦,“固定復方制劑常常在更低的組方劑量下能更好的控制血壓，導致的副作用也更少”“固定復方制劑會更加方便和簡化治療方案，也會比單獨處方不同的藥物花費少?！盝NC 7,“近來多類新型降壓藥問世，新型固定復方制劑涌現(xiàn)如海捷亞等。既有不同作用機制藥物對降壓協(xié)同作用，也使不良反應最小化?！?中國高血壓防治指南（2005修訂版）,新型固定復方制劑,氯沙坦/氫氯噻嗪 （海捷亞）纈沙坦/氫氯噻嗪

15、 （復代文）厄貝沙坦/氫氯噻嗪 （安博諾）（依倫平）,強效快速，控制血壓耐受性好，與安慰劑相似獨特保護, 獨特的腦卒中保護,新型固定復方制劑:氯沙坦/氫氯噻嗪,,ARB氯沙坦+小劑量利尿劑,聯(lián)合用藥-降壓更快速,使用海捷亞第一周即可降低SBP16mmHg,Adapted from Julian Critchley A.J.H. et al., Current Therapeutic Research 57:392-40

16、7, 1996,氯沙坦 + HCTZ (N=426),氨氯地平 + HCTZ (N=419),,,*,*,*,*,基線,治療周,Volpe et al Vol. 25, No. 5, 2003, Page(s) 1469-1489,*P<0.001 vs. 基線,坐位收縮壓 (mmHg),聯(lián)合用藥強效降壓：,,,,,,,,,,,,,,,,,,,,,,,,,,171.9,148.9,144.7,143.8,171.2,151.3,1

17、46.2,143.8,140,145,150,155,160,165,170,175,0,6,12,18,提高血壓控制率,對已經(jīng)用纈沙坦單藥治療失敗者，海捷亞血壓控制率（SiDBP ≤ 90 mmHg）高達72％！,,,,ARB纈沙坦+小劑量利尿劑,,,,,,,-8.6,-8.8,,,,,-7.2,-7.3,,,-11.8,-16.5,,,,,,,,,,,-18,-16,-14,-12,-10,-8,-6,-4,-2,0,纈沙坦,80m

18、g,HCTZ 12.5mg,復代文（纈沙坦80mg/HCTZ 12.5mg）,,,,,,舒張壓,,收縮壓,復代文（纈沙坦/氫氯噻嗪）降壓療效顯著,JR Benz, HR Black, A Graff, et al，J Hum Hypertens, Dec 1998; 12(12): 861-6.,Benz在871例輕中度高血壓患者中進行的雙盲安慰劑對照研究,與基線相比血壓的改變mmHg,復代文（纈沙坦/氫氯噻嗪）的降壓療效優(yōu)于雙倍

19、劑量氫氯噻嗪,Schmidt,et al. Blood Press2001;10:230,與基線相比血壓的改變mmHg,,,,,,,,,,,,,,,,,,,-16,-14,-12,-10,-8,-6,-4,-2,0,,HCTZ 25mg,,,,,,收縮壓,,舒張壓,復代文（纈沙坦80mg/HCTZ 12.5mg）,- 5.7,- 6.8,- 14.9,- 11.2,Schmidt在217 例輕中度高血壓患者中進行的雙盲安慰劑對照研

20、究,,,,,,,,,,,,,,,,,,,,,,,,,,-17.1,-15.7,-17,-11.7,-13.1,-12.8,-12.3,-12.5,-18,-16,-14,-12,-10,-8,-6,-4,-2,0,98,周,114,周,130,周,146,周,血壓下降平均值,(mmHg),,收縮壓,,舒張壓,SG Chrysant,DG Wombolt,et al.Current Therapeutic Research.1998(59

21、):762-772,長期服用復代文（纈沙坦/氫氯噻嗪），降壓療效穩(wěn)定,Chrysant 對73例服用復代文（纈沙坦/氫氯噻嗪）的原發(fā)性高血壓患者（33-77歲）進行的3年降壓療效研究。無患者因藥物相關副作用退出研究,*Mean reductions from baseline at end point (12 weeks) in patients with mild to moderate essential hypertension

22、.Mallion JM et al. Blood Press. 2003;12(suppl 1):36-43.,Diovan® and Co-Diovan®:Dose-Responsive Efficacy,,ARB厄貝沙坦+小劑量利尿劑,,,,,厄貝沙坦/HCTZ（安博諾）和單個藥物治療的劑量反應,,,,,,,,,,-16,-14,-12,-10,-8,-6,-4,-2,0,SeDBP 變化(mmHg),K

23、ochar M et al. Am J Hypertens 1999;12:797-805.,每組患者數(shù) n = 40,安慰劑,HCTZ 12.5 mg,厄貝沙坦150 mg安搏維,厄貝沙坦 150 mgHCTZ 12.5 mg安博諾,-3.5,-6.2,-10.2,-15.0,,,降壓的達標的%,,,,,,,,,,,,,,,0,10,20,30,40,50,60,70,80,90,100,反應率,(%),,83.5%,(

24、DBP<85 mmHg),,,安博諾,150mg/ HCTZ 12.5mg,(DBP<90 mmHg),,,94.35%,Littlejohn T III et al. Clin Exp Hypertens 1999;21:1273-95.,厄貝沙坦/HCTZ（安博諾）治療的長期治療反應,,,正?；?有反應者?,,*Trough SeDBP < 90 mmHg?正?；蜉^基礎值下降 of ? 10 mmHg

25、,,,,,,,,,,,,,,,,,,,0,20,40,60,80,100,80,83,81,87,90,87,患者(%),月,6,12,24,N = 1,006,兩制劑其血漿中厄貝沙坦經(jīng)時濃度：,說明兩制劑的藥代動力學參數(shù)相近。且兩制劑的參數(shù)Cmax、AUC0-24、AUC0-∞和Tmax經(jīng)統(tǒng)計學檢驗均無顯著性差異(P>0.05)。（備注： AUC0-∞分別為13.02?1.96μgh/ml和13.12?2.38μgh/ml

26、。 ）,國產(chǎn)厄貝沙坦/氫氯噻嗪（依倫平）與進口厄貝沙坦/氫氯噻嗪 （安博諾）生物等效性比較,兩制劑其血漿中氫氯噻嗪經(jīng)時濃度：,說明兩制劑的藥代動力學參數(shù)相近。且兩制劑的參數(shù)Cmax、AUC0-24、AUC0-∞和Tmax經(jīng)統(tǒng)計學檢驗均無顯著性差異(P>0.05)。（備注: AUC0-∞分別為773.13?127.05ngh/ml和750.26?150.62ngh/ml）,國產(chǎn)厄貝沙坦/氫氯噻嗪（依倫平）與進口厄貝

27、沙坦/氫氯噻嗪 （安博諾）生物等效性比較,試驗結(jié)果表明：受試制劑-南京正大天晴制藥有限公司研制的依倫平與參比制劑－賽諾菲安萬特制藥股份有限公司生產(chǎn)的安博諾具有生物等效性。,國產(chǎn)厄貝沙坦/氫氯噻嗪（依倫平）與進口厄貝沙坦/氫氯噻嗪 （安博諾）生物等效性比較,,血壓下降,利尿劑或CCB,利鈉和血管擴張,RAAS激活,聯(lián)合治療的機制,,,,,,,,聯(lián)合治療,,,,對利尿劑長期應用的擔心

28、 是否增加了糖尿病的風險？ 是否增加了低血鉀現(xiàn)象？,如何看待利尿劑長期應用的安全性？,,,,,,,海捷亞: 不影響血鉀 / 血糖代謝,1 Adapted from Ruilope LM et al Blood Pressure 5:32-40, 19962 Adapted from JNC Arch Intern Med 157:2413-2446, 1997,血鉀,血糖,,,,NS,,,NS,,12周時，礦物質(zhì)參

29、數(shù)自基線*的平均改變,,,,,,,,,,,,,,,,,,,,,-0.1,,,,-0.2,,,,,,,-0.8,-0.6,-0.4,-0.2,0,,自基線的平均改變值,(mmol/L),,,,,科素亞,50mg,(n=59),海捷亞,(n=55),,,,,,LIFE研究中氫氯噻嗪的使用率,Adapted from Dahlöf B J Ann Intern Med 2004;364:413–414.,使用氫氯噻嗪患者的比例 ％,

30、100,80,60,0,40,20,研究月份,48,60,24,36,12,0,阿替洛爾組氯沙坦組,,,72,,N=9193,,降壓獲益及藥物本身的獲益,1、 強化降壓達標才能獲得可能的器官 保護作用。 2、在降壓達標后不同的藥物是有差別的。,,LIFE: 服用藥物患者%,氯沙坦 阿替洛爾 50 mg 9%

31、 10%50 -100mg 含氫氯噻嗪在內(nèi)的其它治療* 68% 63%中斷研究 23% 27%平均劑量 82 mg 79 mg,,*排除ACEIs, AIIAs, beta bl

32、ockers.Dahlöf B et al Lancet 2002;359:995-1003.,,,LIFE: 相似的降壓效果,研究月份,,,,,,,收縮壓,,舒張壓,,平均動脈壓,mmHg,阿替洛爾 145.4 mmHg,氯沙坦 144.1 mmHg,阿替洛爾 80.9 mmHg,氯沙坦 81.3 mmHg,Dahlöf B et al Lancet 2002;359:995-1003.,,阿替洛爾 1

33、02.4 mmHg,氯沙坦 102.2 mmHg,,,,,,,,,,,,Proportion of patients with first event (%),,,0,2,4,6,8,10,12,14,16,,,,,,,,,,,,0,6,12,18,24,30,36,42,48,54,60,66,Adjusted Risk Reduction: 13.0%, p = 0.021,Time (months),Change from b

34、aseline (%) in LVH determined by electrocardiography,,,,,,,,,,,,,-18,-16,-14,-12,-10,-8,-6,-4,-2,0,p < 0.0001,,p < 0.0001,4.4%,10.2%,15.3%,,9.0%,,,AtenololLosartan,Dahlöf B et al. Lancet 2002;359:995–1003.,L

35、VH regression and primary endpoint,,,Atenolol,Losartan,CornellVoltage-Duration Product,Sokolow-LyonVoltage,Composite of CV Death, stroke and MI,,LIFE 研究,VALUE: Major Study End Points in 5006 Patient Pairs (N = 10,0

36、12) on Diovan®- or Amlodipine-Based Therapies Using Serial Median Matching,Composite cardiac events,Stroke,Death,Myocardial infarction,Heart failure,,,,,,,0.6,0.8,1.0,1.2,1.4,,,,,,Favours Diovan,Favours amlodipine,,

37、,,,,,,,,,,,,,,*P<0.05. Weber MA et al. Lancet. 2004;363:2047-2049.,有利于氨氯地平,VALUE:初步結(jié)果顯示，與全球結(jié)果相比，亞洲人群從以纈沙坦為基礎的治療方案中獲益更多。,主要終點的危險比和 95% CIs 總組 (n=15,245) vs 亞洲人群 (n=441),,,,,,有利于纈沙坦,風險比,0.25,0.5,1,2,4,,+,#,總組主要聯(lián)合終點*

38、亞洲人群主要聯(lián)合終點總組心梗亞洲人群心?？偨M充血性心衰亞洲人群充血性心衰總組中風亞洲人群腦卒中總組全因死亡亞洲人群總死亡總組心源性死亡亞洲人群心源性死亡,* 心源性死亡和發(fā)病率+ P<0.05# P=0.054,Julius S et al. Lancet. 2004;363:2022-2031.,VALUE: Diovan®-Based Therapy Significantly Re

39、duces Risk for New-Onset Diabetes,Study Design,W0Visit 1 Enrolment of hypertensive patients untreated or uncontrolled by monotherapy,R,,,HCTZ : 12.5 mg od - 5 weeks,,,W4Visit 2Exclusion if SBP <1

40、40 mm Hg(office),,W13Visit 4Final evaluation,,5 weeks,,8 weeks,Phase 1,Phase 2,COSIMA Study,COSIMA：,? BP [final - baseline] (mm Hg),HBPM(average of all values),DBP,SBP,Office BP(trough),DBP,SBP,P<0.001,P<0.01

41、,Δ2.8(26%),,-16,-12,-8,-4,0,,,,,,Δ2.2(30%),,-16,-12,-8,-4,0,,,,,,P<0.05,P<0.01,Δ3.2(28%),Δ1.4(21%),G. Bobrie et al. Archives Mal Coeur Vaiss 2004 (12): p96 and p116,-9.6,-7.4,-13.4,-10.6,-8.2,-6.8,-14.8,-11.6,Signi

42、ficantly More Patients Normalisedon Irbesartan Combination Therapy*,% Patients,P<0.0001,Office,HBPM,,,,,,,P<0.05,Normal HBPM values:SBP <135 mm Hg andDBP <85 mm Hg,Normal office values:SBP <140 mm Hg a

43、ndDBP <90 mm Hg,Δ19.6%,Δ10.3%,Data on file,52.9%,33.3%,51.5%,41.2%,*The PP results are consistent with the ITT results8 week study,COSIMA Study,,Minimum4 weeks,,1,005 Uncontrolledon SingleAntihypertensiveAgent,I

44、NCLUSIVE: Study Design,Multicenter (119 sites across the US), prospective, open-label, single-arm study,Screening,,,,,Intent-to-treat (ITT) population, n = 736.Week 18 aggregate data for irbesartan/HCTZ 150/12.5 mg and

45、300/25 mg include all patients whose BP was controlled from baseline.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 mmH

46、g; 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; D

47、BP = diastolic blood pressure; SBP = systolic blood pressure.,DBP Goal,,SBP Goal,INCLUSIVE Blood Pressure Goal Attainment at Week 18,ITT population; T2DM, type 2 diabetes mellitus,Elderly(n=184),African-American(n=15

48、7),Hispanic/Latino(n=110),T2DM(n=227),Metabolicsyndrome(n=345),Women(n=370),Men(n=366),<130 mm Hg,,,,,,,,,,,,,,,,,73%,73%,72%,75%,82%,73%,56%,0,20,40,60,80,100,Patients Controlled (%),Elderly(n=184),African-A

49、merican(n=157),Hispanic/Latino(n=110),T2DM(n=227),Metabolicsyndrome(n=345),Women(n=370),Men(n=366),<80 mm Hg,,,,,,,,,,,,,,,,,80%,96%,78%,83%,86%,77%,63%,0,20,40,60,80,100,Patients Controlled (%),SBP 亞組達標率,DBP

50、 亞組達標率,<130,<80,INCLUSIVE,,ARB聯(lián)合利尿劑的優(yōu)勢,,,,,血管緊張素 I,血管緊張素（肝）,,,血管緊張素 II,ARBAT1 受體拮抗劑,,,Adapted from: de Gasparo et al. Pharmacol Rev. 2000; 52: 415,ACE,ARB作用示意圖,血管舒張抗增殖作用凋亡,Clinical Significance of AT1 Recepto

51、r Blockade,,,,,,A II,AT2,,?BP,?Atherosclerosis,?EndothelialFunction,?Neuroendocrine,?LVH,,,,,,,,,CardioprotectionVasculoprotectionRenoprotection,,,AT1 receptor blockade,A II binding at the AT2 receptor,,,,,,ARB,LVH=l

52、eft ventricular hypertrophy.,AT1,,氯沙坦有效逆轉(zhuǎn)向心性LVH,氯沙坦可使47.4%患者LVMI恢復正常，向心性LVH比例從38.9%降至6.7%向心性LVH的危險性比離心性LVH高,38.9%,6.7%,,,47.4%,CVF = 9.8%,CVF = 2.7%,氯沙坦抑制膠原合成和心肌纖維化,基線,氯沙坦治療12個月,CVF = 膠原容量比例,Diez et al. Circulation 2002

53、;105:2512–2517.,Baseline,,,,,,,During Treatment,,,,,,,,3.95,3.9,3.85,3.8,3.75,3.7,3.65,P<0.001,LosartanAtenolol,,,LIFE 研究,,,Months in LIFE,Left Atria diameter (cm),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

54、,,,,,,,,,,3.55,3.6,3.65,3.7,3.75,3.8,3.85,3.9,3.95,4,,,,,,,,0,12,24,36,48,60,,,Losartan,,Atenolol,P=0.86,P=0.003,P=0.077,P=0.025,P=0.002,P=0.01,科素亞與阿替洛爾治療對左房內(nèi)徑的影響,纈沙坦 vs氨氯地平: 纈沙坦改善內(nèi)皮功能,,,,,,,,60,40,20,0,10,30,50,70,,,,,6

55、2%*,13%,% 乙酰膽堿刺激后前臂血流量的改變,纈沙坦,氨氯地平,Adapted with permission from Tzemos N et al. Am J Hypertens. 2001;14:A66-A67.0,,*P <0.05 vs 基線,代文®增加內(nèi)皮NO的產(chǎn)生和釋放，改善血管內(nèi)皮功能,Klingbeil AU, et al. Am J Hypertens 2003;16:123–8,,,,,,,,

56、,–0.6,–0.4,–0.2,0,0.2,代文 80 mg HCTZ 25 mg 安慰劑,NG-單甲基-L-精氨酸刺激后前臂血流量變化* (mL/min/100 mL),服用氫氯噻嗪治療無明顯變化,,–0.6? (n=20),0.2(n=20),(n=20),?p<0.05 vs安慰劑,Valsartan Improves Insulin Sensitivityin

57、 Hypertensive Patients,Top C, et al. J Internat Med Res. 2002;30:15–20.,Normotensive (20)Hypertensive (20)Pre-TreatmentHypertensivePost-Treatment(valsartan 80 mg),,,,,,,,Fasting Insulin(uIU/mL),,,,,,,,,,,,,,,,,,,,0

58、,65,70,75,80,85,90,95,,,,,,,,,,,,,,纈沙坦,安慰劑,,100,p=0.009,無事件概率 (%),,,,,,,,13.2%,一級聯(lián)合終點,,,,,,,,,,,,0,65,70,75,80,85,90,95,,,,,100,p<0.00001,,,,,,,,,,,,,,,纈沙坦,安慰劑,,,,27.5%,心衰再住院率,,,,,,,,,,,,,,** p<0.00002,無事件生存率,,,,,,

59、,,,,,纈沙坦 n = 185,安慰劑 n = 181,,,,44%,未使用ACEI組代文可使一級聯(lián)合終點降低44%,Val- HeFT 的主要終點事件,Val-HeFT: 左室功能的超聲心動指標,纈沙坦,安慰劑,,,LVIDd/BSA變化(cm/m2),EF變化(%),,,,,,,,,,2.0,3.0,4.0,5.0,,,,,,,,,–0.12,–0.08,–0.04,0.00,4 Months,12 Months,18

60、Months,24 Months,,,,,,,,,,,,,,,,,P < 0.0001,P < 0.001,P < 0.0001,P = 0.031,P < 0.001,P < 0.0001,P < 0.0001,P = 0.033,,,Wong M et al. J Am Coll Cardiol. 2002;40:970?975.,Val-HeFT 試驗,IRMA2:安博維?300mg顯著降低患

61、者發(fā)生糖尿病腎病的危險性,Parving H-H, et al. N Engl J Med2001;345:870-878.,0,5,10,15,20,0,3,6,12,18,22,24,,,,隨訪時間 (月),患者比例 (%),對照組安博維® 150 mg安博維® 300 mg,,,,,RRR 70%P<0.001,,,,5.2%,9.7%,14.9%,,70%,IRMA2: 安博維?使34%患者尿白

62、蛋白排泄率恢復正常,Parving H-H, et al. N Engl J Med2001;345:870-878.,安博維?,,,,,,,,,,,40,30,20,10,0,對照組(n=201),150 mg(n=195),300 mg(n=194),,24,34,21,P=0.006,,,,,患者比例 (%),IDNT: 安博維?顯著降低到達主要終點的危險性20%,,,,0,0,25,50,75,12,24,36,48,

63、,,安博維® 300mg組（n=570）,,氨氯地平10mg組（n=567）,,隨訪時間（月）,,對照組（n=569）,VS,,,安博維®,20%,p＝0.02,,*主要終點：血清肌酐升高達2倍、終末期腎病或各種原因引起的死亡,與氨氯地平相比，安博維®降低到達主要終點的危險性23%, p=0.006,治療時間:2.6年,到達主要終點*的患者比例（％）,Lewis EJ, et al. N Engl

64、J Med(《新英格蘭雜志》). 2001; 345: 851-860.,60,Soffer et al. Hypertension 1995, 26 (1): 112-117,科素亞+利尿劑（海捷亞）也不影響尿酸代謝,血清尿酸, mmol/L,*,*,* P<0.01,,,,,,,,,,,,,,,,,,,,,,-30,-25,-20,-15,-10,-5,0,5,10,15,氯沙坦25mg /HCTZ25mg,*,

65、氯沙坦50mg /HCTZ25mg,氯沙坦100mg /HCTZ25mg,安慰劑 /HCTZ25mg,氯沙坦平衡低劑量利尿劑對代謝影響,新型固定復方制劑中國專家共識,無并發(fā)癥1、2級高血壓患者，及老年收縮期高血壓、合并糖尿病或代謝綜合征的高血壓患者，推薦ARB/HCTZ固定復方制劑。未服藥的患者，ARB/HCTZ固定復方制劑可作為初始治療。對已獲得控制的高血壓患者ARB/HCTZ固定復方制劑可作為