高血压治疗的坚持与改变

1、高血压治疗的坚持与改变“Quality first”From ambiguous to clear recommendations The “Quality First” approach降低整个动脉系统的血压（中心动脉压vs肱动脉血压）降低24小时血压（晨峰血压）不宜太低，不宜太快（应遵循个体化原则）多重危险因素干预（降脂、降糖、戒烟）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: 晨峰血压的预测价值Li Y, et al. Hypertension 2010; in press. The “Quality First” approach选择有效药物，实现降压达标选择长效降压药物，控制24小时血压选择能够长期坚持使用的药物，长期、平稳控制血压选择作用于血管的降压药物“Quality first”From ambiguous to clear recommendations Possible combinations of antihype

9、rtensive drugs J Hypertens 2007;25:1105-87.Thiazide diureticsACEIsARBsCCBs-blockers-blockersJNC指南推荐的降压治疗起始药物指南制定年份推荐药物JNC 11977噻嗪类利尿剂JNC 21980利尿剂JNC 31984噻嗪类利尿剂或阻滞剂JNC 41988噻嗪类利尿剂 或 阻滞剂 或 CCB 或 ACEIJNC 51993利尿剂或阻滞剂JNC 61997利尿剂或阻滞剂JNC 72003噻嗪类利尿剂JNC 82009？NICE/BHS (2006)：降压药物推荐A: ACEI or ARB B: -阻滞剂

10、C: CCB D: 利尿剂 (噻嗪类)Step 4 顽固性 HT加用: a- 阻滞剂 or 螺内酯 or 其它降压药物Step 3+ACD+年龄 (55岁)或黑人Step 1AC or DStep 2+AC or D* 与其它联合治疗方案相比，阻滞剂与利尿剂联合治疗方案会增加新发糖尿病风险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: 主要终点及组成复合CV发病率/死亡率心血管死亡率心梗中风不稳定心绞痛住院冠状动脉成形术猝死复苏成功危险比 (95%)Aml / Ben较好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较好Jamerson K et al. N Engl J Med 2008;359:2417-28.ASCOT-BPLA：一、二级

12、终点0.500.701.001.45主要终点 非致死性MI(包括症状MI)+致死性冠心病 次要终点非致死性MI(除外无症状MI)+ 致死性冠心病总的冠心病终点事件总的心血管病事件和操作总死亡率 心血管病死亡率 致死性和非致死性脑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.氨氯地平培哚普利较好阿替洛尔苄氟噻嗪较好 相对危险度(95% CI)赖诺普利较好氨氯地平较好 +1% (9% to +11%)CHD +5% (3% to +13%) 总死亡率 +4% (3% to +12%) 联合CHD 脑卒中 联合CVD 需要住院的GI出血心衰 心绞痛 冠脉血运重建 外周动脉疾病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 终点事件 差别 (95% CI)Leenen FHH, et al. Hypertension 2006;48:374-384.ALLHAT：赖诺普利 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缬沙坦组氨氯地平HR = 1.19; 95% CI = 1.02-1.38; P = 0.02 Julius S et al. Lancet. June 2004;363.19CCBs vs. 利尿剂/阻滞剂: 致死性与非致死性脑卒中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较好利尿剂/阻滞剂较好利尿剂/阻滞剂试验事件数 / 研究对象人数异质性检验 危险比 (95%可信区间)差别 (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：主要终点事件Liu LS et al. J Hypertens 2005;23:2157-2172.02468100612182430364248546026.8%HCTZ非洛地平+HCTZ随访时间（月）主要终点（%）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