高血壓治療的堅(jiān)持與改變

1、高血壓治療的堅(jiān)持與改變“Quality first”From ambiguous to clear recommendations The “Quality First” approach降低整個(gè)動(dòng)脈系統(tǒng)的血壓（中心動(dòng)脈壓vs肱動(dòng)脈血壓）降低24小時(shí)血壓（晨峰血壓）不宜太低，不宜太快（應(yīng)遵循個(gè)體化原則）多重危險(xiǎn)因素干預(yù)（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(yù)測(cè)價(jià)值Li Y, et al. Hypertension 2010; in press. The “Quality First” approach選擇有效藥物，實(shí)現(xiàn)降壓達(dá)標(biāo)選擇長效降壓藥物，控制24小時(shí)血壓選擇能夠長期堅(jiān)持使用的藥物，長期、平穩(wěn)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(nèi)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(lián)合治療方案相比，阻滯劑與利尿劑聯(lián)合治療方案會(huì)增加新發(fā)糖尿病風(fēng)險(xiǎn)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(diǎn)及組成復(fù)合CV發(fā)病率/死亡率心血管死亡率心梗中風(fēng)不穩(wěn)定心絞痛住院冠狀動(dòng)脈成形術(shù)猝死復(fù)蘇成功危險(xiǎn)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(jí)

12、終點(diǎn)0.500.701.001.45主要終點(diǎn) 非致死性MI(包括癥狀MI)+致死性冠心病 次要終點(diǎn)非致死性MI(除外無癥狀MI)+ 致死性冠心病總的冠心病終點(diǎn)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(duì)危險(xiǎn)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(lián)合CHD 腦卒中 聯(lián)合CVD 需要住院的GI出血心衰 心絞痛 冠脈血運(yùn)重建 外周動(dòng)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(diǎn)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(yàn)事件數(shù) / 研究對(duì)象人數(shù)異質(zhì)性檢驗(yàn) 危險(xiǎn)比 (95%可信區(qū)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(diǎn)事件Liu LS et al. J Hypertens 2005;23:2157-2172.02468100612182430364248546026.8%HCTZ非洛地平+HCTZ隨訪時(shí)間（月）主要終點(diǎn)（%）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