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高血压治疗的坚持与改变

高血压治疗的坚持与改变. 上海交通大学医学院附属瑞金医院 上海市高血压研究所 王继光 jiguangw@gmail.com. “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).

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高血压治疗的坚持与改变

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  1. 高血压治疗的坚持与改变 上海交通大学医学院附属瑞金医院 上海市高血压研究所 王继光 jiguangw@gmail.com

  2. “Quality first” • From ambiguous to clear recommendations

  3. 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）

  4. Systolic pressures (mean + 95% CI) Average : 133.5 Standard vs. 119.3 Intensive, Delta = 14.2 Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3

  5. Diastolic Pressures (mean + 95% CI) Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3

  6. Primary & secondary outcomes Also examined fatal/Nonfatal HF (HR=0.94, p=0.67), a composite of fatal coronary 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)

  7. Primary outcome Nonfatal MI, Nonfatal Stroke or CVD Death Total stroke HR = 0.89 95% CI (0.73-1.07) HR = 0.59 95% CI (0.39-0.89) NNT for 5 years = 89

  8. Mean Sitting BP McMurray JJ et al. N Engl J Med 2010.

  9. Extended and core CV outcomes Placebo 693 events (14.8%) Valsartan 672 events (14.5%) Placebo 377 events (8.1%) Valsartan 375 events (8.1%) McMurray JJ et al. N Engl J Med 2010.

  10. Exploratory outcomes: CV & total mortality Placebo 327 events (7.0%) Valsartan 295 events (6.4%) Placebo 116 events (2.5%) Valsartan 128 events (2.8%) McMurray JJ et al. N Engl J Med 2010.

  11. Adverse events of interest *MedDRA preferred terms include: hypotension, dizziness (including dizziness exertional, dizziness postural), syncope, presyncope and shock (not otherwise specified) McMurray JJ et al. N Engl J Med 2010.

  12. IDACO: 晨峰血压的预测价值 Li Y, et al. Hypertension 2010; in press.

  13. 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

  14. “Quality first” • From ambiguous to clear recommendations

  15. Possible combinations of antihypertensive drugs Thiazide diuretics -blockers ARBs CCBs -blockers ACEIs J Hypertens 2007;25:1105-87.

  16. JNC指南推荐的降压治疗起始药物

  17. 年龄 (<55岁) 年龄 (>55岁) 或黑人 Step 1 A C or D Step 2 A C or D + A C D Step 3 + + Step 4顽固性 HT 加用: a- 阻滞剂 or 螺内酯 or 其它降压药物 NICE/BHS (2006)：降压药物推荐 A: ACEI or ARB B: β-阻滞剂 C: CCB D: 利尿剂 (噻嗪类) * 与其它联合治疗方案相比，β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 hypertension in adults in primary care: partial update. London: Royal College of Physicians, 2006.

  18. ACCOMPLISH: 主要终点及组成 危险比 (95%) 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 0.80 (0.72–0.90) 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) Aml / Ben 较好 Ben / HCTZ较好 2.0 0.5 1.0 Jamerson K et al. N Engl J Med 2008;359:2417-28.

  19. ASCOT-BPLA：一、二级终点 Unadjusted 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) 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 氨氯地平 培哚普利较好 阿替洛尔 苄氟噻嗪较好 1.00 1.45 2.00 0.50 0.70 Dahlöf B et al. Lancet 2005:366;895-906.

  20. ALLHAT：赖诺普利 vs. 氨氯地平 相对危险度 (95% CI) 差别 (95% CI) 终点事件 CHD +1% (–9% to +11%) 总死亡率 +5% (–3% to +13%) +4% (–3% to +12%) 联合CHD +23% (+8% to +41%) P=0.003 脑卒中 +6% ( 0 to +12%) P=0.047 联合CVD P=0.004 +20% (+6% to +37%) 需要住院的GI出血 心衰 -13% (–22% to –4%) P=0.007 心绞痛 +9% ( 0 to +19%) P=0.055 冠脉血运重建 0 (–9% to +11%) 外周动脉疾病 +19% (+1% to +40%) P= 0.036 赖诺普利较好 氨氯地平较好 0.5 2.0 1.0 Leenen FHH, et al. Hypertension 2006;48:374-384.

  21. VALUE: 致死及非致死心肌梗死 7 6 5 4 3 2 1 0 19％ 缬沙坦组 氨氯地平 % of patients with 1st event HR = 1.19; 95% CI = 1.02-1.38; P = 0.02 0 6 12 18 24 30 36 42 48 54 60 66 Months Number at risk Valsartan 7649 7499 7458 7319 7177 7016 6853 6680 6504 6078 3864 1520 Amlodipine 7596 7497 7458 7332 7205 7065 6905 6727 6562 6141 3840 1532 Julius S et al. Lancet. June 2004;363.

  22. CCBs vs.利尿剂/阻滞剂: 致死性与非致死性脑卒中 试验 事件数 / 研究对象人数 差别 (SD) 异质性检验 危险比 (95%可信区间) 利尿剂/阻滞剂 CCBs 15/1358 237/2213 196/5471 74/3164 675/15255 14/1157 1211/28618 118/8297 1329/36915 19/1353 207/2196 159/5410 67/3157 377/9048 9/1177 838/22341 133/8179 971/30520 MIDAS/NICS/VHAS STOP2/CCBs NORDIL/Diltiazem INSIGHT/Nifedipine GITS ALLHAT/Amlodipine ELSA/Lacidipine CCBs without CONVINCE p = 0.68 CONVINCE/Verapamil SR All CCBs p = 0.39 –10.2% (4.8) 2p = 0.02 –7.6% (4.4) 2p = 0.07 3 0 1 2 利尿剂/阻滞剂较好 CCBs较好 Staessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76.

  23. Syst-China: Fatal and non-fatal endpoints Placebo (n=1141) Active treatment (n=1253) 82 44 20 94 59 61 33 10 74 45 Total mortality CV mortality Stroke mortality All CV events Fatal and non-fatal stroke 82 44 20 94 59 61 33 10 74 45 -39 -39 -58 -37 -38 – 80 – 40 0 + 40% Active treatment better Placebo better Liu LS et al. J Hypertens 1998;16:1823-1829.

  24. FEVER：主要终点事件 HCTZ 非洛地平+HCTZ 10 8 ↓26.8% 主要终点（%） 6 4 2 0 0 30 36 42 48 54 60 24 6 12 18 随访时间（月） Liu LS et al. J Hypertens 2005;23:2157-2172.

  25. Chinese Hypertension Intervention Efficacy (CHIEF)：General design Amlodipine 2.5 mg/d +telmisartan 40 mg/d Hypertensive patients at high CV risk (n=12,000) Amlodipine 2.5 mg/d +amiloride 1.25/ HCTZ 12.5 mg/d 4y 0y 1y 2y 3y Primary endpoint: CV death, stroke and MI

  26. Clear recommendations • If no compelling indications or contraindications, simply start with CLASSIC (Amlodipine), with the possible replacement of or combination with FASHION (ARB/ACEI). • The A+A partnership.

  27. Thank you very much ！

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