1、高血壓治療的堅持與改變“Quality first”From ambiguous to clear recommendations The “Quality First” approach降低整個動脈系統的血壓（中心動脈壓vs肱動脈血壓）降低24小時血壓（晨峰血壓）不宜太低，不宜太快（應遵循個體化原則）多重危險因素干預（降脂、降糖、戒煙）Systolic pressures (mean + 95% CI)Average : 133.5 Standard vs. 119.3 Intensive, Delta = 14.2Mean # Meds Intensive: 3.2 3.4 3.5 3.4

2、 Standard: 1.9 2.1 2.2 2.3Diastolic Pressures (mean + 95% CI)Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3Primary & secondary outcomes Intensive Events (%/yr)StandardEvents (%/yr)HR (95% CI)PPrimary208 (1.87)237 (2.09)0.89 (0.73-1.07)0.20Total Mortality150 (1.28)144 (1.19)1.07 (0.

3、85-1.35)0.55Cardiovascular Deaths60 (0.52)58 (0.49)1.06 (0.74-1.52)0.74Nonfatal MI126 (1.13)146 (1.28)0.87 (0.68-1.10)0.25Nonfatal Stroke34 (0.30)55 (0.47)0.63 (0.41-0.97)0.03Total Stroke36 (0.32)62 (0.53)0.59 (0.39-0.89)0.01Also examined fatal/Nonfatal HF (HR=0.94, p=0.67), a composite of fatal cor

4、onary events, nonfatal MI and unstable angina (HR=0.94, p=0.50) and a composite of the primary outcome, revascularization and unstable angina (HR=0.95, p=0.40)Primary outcome Nonfatal MI, Nonfatal Stroke or CVD DeathTotal strokeHR = 0.8995% CI (0.73-1.07)HR = 0.5995% CI (0.39-0.89)NNT for 5 years =

5、89Mean Sitting BPMcMurray JJ et al. N Engl J Med 2010.Extended and core CV outcomesPlacebo693 events (14.8%)Valsartan672 events (14.5%)Placebo377 events (8.1%)Valsartan375 events (8.1%)McMurray JJ et al. N Engl J Med 2010.Exploratory outcomes: CV & total mortalityPlacebo327 events (7.0%)Valsartan295

6、 events (6.4%)Placebo116 events (2.5%)Valsartan128 events (2.8%)McMurray JJ et al. N Engl J Med 2010.McMurray JJ et al. N Engl J Med 2010.Adverse events of interestValsartann=4631n (%)Placebon=4675n (%)P ValueHypotension-related*1964 (42.4)1680 (35.9)0.001Hypertension693 (15.0)950 (20.3)0.001Renal d

7、ysfunction136 (2.9)146 (3.1)0.55Hyperkalemia35 (0.8)35 (0.7)0.99Hypokalemia45 (1.0)84 (1.8)0.001Hypoglycemia731 (15.8)707 (15.1)0.39Hyperglycemia45 (1.0)44 (0.9)0.93Angioedema89 (1.9)123 (2.6)0.02*MedDRA preferred terms include: hypotension, dizziness (including dizziness exertional, dizziness postu

8、ral), syncope, presyncope and shock (not otherwise specified)IDACO: 晨峰血壓的預測價值Li Y, et al. Hypertension 2010; in press. The “Quality First” approach選擇有效藥物，實現降壓達標選擇長效降壓藥物，控制24小時血壓選擇能夠長期堅持使用的藥物，長期、平穩控制血壓選擇作用于血管的降壓藥物“Quality first”From ambiguous to clear recommendations Possible combinations of antihype

9、rtensive drugs J Hypertens 2007;25:1105-87.Thiazide diureticsACEIsARBsCCBs-blockers-blockersJNC指南推薦的降壓治療起始藥物指南制定年份推薦藥物JNC 11977噻嗪類利尿劑JNC 21980利尿劑JNC 31984噻嗪類利尿劑或阻滯劑JNC 41988噻嗪類利尿劑 或 阻滯劑 或 CCB 或 ACEIJNC 51993利尿劑或阻滯劑JNC 61997利尿劑或阻滯劑JNC 72003噻嗪類利尿劑JNC 82009？NICE/BHS (2006)：降壓藥物推薦A: ACEI or ARB B: -阻滯劑

10、C: CCB D: 利尿劑 (噻嗪類)Step 4 頑固性 HT加用: a- 阻滯劑 or 螺內酯 or 其它降壓藥物Step 3+ACD+年齡 (55歲)或黑人Step 1AC or DStep 2+AC or D* 與其它聯合治療方案相比，阻滯劑與利尿劑聯合治療方案會增加新發糖尿病風險National Collaborating Centre for Chronic Conditions. Hypertension: management of hypertensionin adults in primary care: partial update. London: Royal Coll

11、ege of Physicians, 2006.0.51.02.0ACCOMPLISH: 主要終點及組成復合CV發病率/死亡率心血管死亡率心梗中風不穩定心絞痛住院冠狀動脈成形術猝死復蘇成功危險比 (95%)Aml / Ben較好0.80 (0.720.90)0.80 (0.62-1.03)0.78 (0.62-0.99)0.84 (0.65-1.08)0.75 (0.50-1.10)0.86 (0.74-1.00)1.75 (0.73-4.17)Ben / HCTZ較好Jamerson K et al. N Engl J Med 2008;359:2417-28.ASCOT-BPLA：一、二級

12、終點0.500.701.001.45主要終點 非致死性MI(包括癥狀MI)+致死性冠心病 次要終點非致死性MI(除外無癥狀MI)+ 致死性冠心病總的冠心病終點事件總的心血管病事件和操作總死亡率 心血管病死亡率 致死性和非致死性腦卒中致死性和非致死性心力衰竭 2.00Unadjusted Hazard ratio (95% CI)0.90 (0.79-1.02)0.87 (0.76-1.00)0.87 (0.79-0.96)0.84 (0.78-0.90)0.89 (0.81-0.99)0.76 (0.65-0.90)0.77 (0.66-0.89)0.84 (0.66-1.05)Dahlf B

13、 et al. Lancet 2005:366;895-906.氨氯地平培哚普利較好阿替洛爾芐氟噻嗪較好 相對危險度(95% CI)賴諾普利較好氨氯地平較好 +1% (9% to +11%)CHD +5% (3% to +13%) 總死亡率 +4% (3% to +12%) 聯合CHD 腦卒中 聯合CVD 需要住院的GI出血心衰 心絞痛 冠脈血運重建 外周動脈疾病0.51.02.0 +23% (+8% to +41%) +6% ( 0 to +12%) +20% (+6% to +37%) -13% (22% to 4%) +9% ( 0 to +19%) 0 (9% to +11%) +19

14、% (+1% to +40%) P=0.055 P=0.047 P=0.003 P=0.007 P=0.004 P= 0.036 終點事件 差別 (95% CI)Leenen FHH, et al. Hypertension 2006;48:374-384.ALLHAT：賴諾普利 vs. 氨氯地平MonthsNumber at riskValsartanAmlodipine759676497497749974587458733273197205717769056853706570166727668061416078384038641532152065626504% of patients wi

15、th 1st event76543210VALUE: 致死及非致死心肌梗死0612182430364248546066纈沙坦組氨氯地平HR = 1.19; 95% CI = 1.02-1.38; P = 0.02 Julius S et al. Lancet. June 2004;363.19CCBs vs. 利尿劑/阻滯劑: 致死性與非致死性腦卒中0123MIDAS/NICS/VHASSTOP2/CCBsNORDIL/Diltiazem INSIGHT/Nifedipine GITSALLHAT/AmlodipineELSA/Lacidipine CCBs without CONVINCEp

16、 = 0.68CONVINCE/Verapamil SR All CCBsp = 0.3915/1358237/2213196/547174/3164675/1525514/11571211/28618118/82971329/3691519/1353207/2196159/541067/3157377/90489/1177838/22341133/8179971/3052010.2% (4.8) 2p = 0.027.6% (4.4) 2p = 0.07CCBs較好利尿劑/阻滯劑較好利尿劑/阻滯劑試驗事件數 / 研究對象人數異質性檢驗 危險比 (95%可信區間)差別 (SD)CCBsStae

17、ssen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76. 80 400+ 40%Syst-China: Fatal and non-fatal endpointsLiu LS et al. J Hypertens 1998;16:1823-1829.Placebo(n=1141)Total mortalityCV mortalityStroke mortalityAll CV eventsFatal and non-fatal strokeActive treatment(n=

18、1253)Placebo better82442094596133107445Active treatment better-39-39-58-37-3882442094596133107445FEVER：主要終點事件Liu LS et al. J Hypertens 2005;23:2157-2172.02468100612182430364248546026.8%HCTZ非洛地平+HCTZ隨訪時間（月）主要終點（%）Chinese Hypertension Intervention Efficacy (CHIEF)：General designHypertensive patients at high CV risk (n=12,000) Amlodipine 2.5 mg/d+telmisartan 40 mg/dAmlodipine 2.5 mg/d+amiloride 1.25/ HCTZ