1、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o“Quality first”oFrom ambiguous to clear recommendations The“Quality First”approachn降低整个动脉系统的血压(中心动脉压降低整个动脉系统的血压(中心动脉压vs肱动脉血压)肱动脉血压)n降低降低24小时血压(晨峰血压)小时血压(晨峰血压)n不宜太低,不宜太快(应遵循个体化原则)不宜太低,不宜太快(应遵循个体化原则)n多重危险因素干预(降脂、降糖、戒烟)多重危险因素干预(降脂、降糖、戒烟)Systolic pressur
2、es(mean+95%CI)Average:133.5 Standard vs.119.3 Intensive,Delta=14.2Mean#Meds Intensive:3.2 3.4 3.5 3.4 Standard:1.9 2.1 2.2 2.3Patients with Events(%)05101520Years Post-Randomization012345678Patients with Events(%)05101520Years Post-Randomization012345678Primary outcome Nonfatal MI,Nonfatal Stroke or
3、 CVD DeathTotal strokeHR=0.8995%CI(0.73-1.07)HR=0.5995%CI(0.39-0.89)NNT for 5 years=89Mean Sitting BPMcMurray JJ et al.N Engl J Med 2010.Extended and core CV outcomesPlacebo693 events(14.8%)Valsartan 672 events(14.5%)Placebo377 events(8.1%)Valsartan375 events(8.1%)McMurray JJ et al.N Engl J Med 2010
4、.Exploratory outcomes:CV&total mortalityPlacebo327 events(7.0%)Valsartan295 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*196
5、4(42.4)1680(35.9)0.001Hypertension693(15.0)950(20.3)0.001Renal dysfunction136(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,dizzines
6、s(including dizziness exertional,dizziness postural),syncope,presyncope and shock(not otherwise specified)IDACO:晨峰血压的预测价值晨峰血压的预测价值Li Y,et al.Hypertension 2010;in press.The“Quality First”approachn选择有效药物,实现降压达标选择有效药物,实现降压达标n选择长效降压药物,控制选择长效降压药物,控制24小时血压小时血压n选择能够长期坚持使用的药物,长期、平稳控制血压选择能够长期坚持使用的药物,长期、平稳控制血
7、压n选择作用于血管的降压药物选择作用于血管的降压药物o“Quality first”oFrom ambiguous to clear recommendations Possible combinations of antihypertensive 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 419
8、88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:降压药物推荐A:ACEI or ARB B:阻滞剂阻滞剂 C:CCB D:利尿剂利尿剂(噻嗪类噻嗪类)加用:-阻滞剂 or 螺内酯 or 其它降压药物+ACD+年龄(55岁)或黑人*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:ma
9、nagement of hypertensionin adults in primary care:partial update.London:Royal College of Physicians,2006.ACCOMPLISH:主要终点及组成主要终点及组成Aml/Ben较好较好Ben/HCTZ较好较好Jamerson K et al.N Engl J Med 2008;359:2417-28.ASCOT-BPLA:一、二级终点:一、二级终点0.500.701.001.45主要终点主要终点 非致死性非致死性MI(MI(包括症状包括症状MI)+MI)+致死性冠心病致死性冠心病 次要终点次要终点
10、非致死性非致死性MI(MI(除外无症状除外无症状MI)MI)+致死性冠心病致死性冠心病总的冠心病终点事件总的冠心病终点事件总的心血管病事件和操作总的心血管病事件和操作总死亡率总死亡率 心血管病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脑卒中致死性和非致死性心力衰竭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.
11、66-1.05)Dahlf B et al.Lancet 2005:366;895-906.氨氯地平氨氯地平 培哚普利较好培哚普利较好阿替洛尔阿替洛尔 苄氟噻嗪较好苄氟噻嗪较好 相对危险度相对危险度(95%CI)赖诺普利赖诺普利较好较好氨氯地平氨氯地平较好较好+1%(9%to+11%)CHD+5%(3%to+13%)总死亡率总死亡率+4%(3%to+12%)联合联合CHD 脑卒中脑卒中 联合联合CVD 需要住院的需要住院的GI出血出血心衰心衰 心绞痛心绞痛 冠脉血运重建冠脉血运重建 外周动脉疾病外周动脉疾病0.51.02.0+23%(+8%to+41%)+6%(0 to+12%)+20%(+6
12、%to+37%)-13%(22%to 4%)+9%(0 to+19%)0 (9%to+11%)+19%(+1%to+40%)P=0.055 P=0.047 P=0.003 P=0.007 P=0.004 P=0.036 终点事件终点事件 差别差别(95%CI)Leenen FHH,et al.Hypertension 2006;48:374-384.ALLHAT:赖诺普利:赖诺普利 vs.氨氯地平氨氯地平MonthsNumber at riskValsartanAmlodipine759676497497749974587458733273197205717769056853706570166
13、727668061416078384038641532152065626504%of patients with 1st event76543210VALUE:致死及非致死心肌梗死致死及非致死心肌梗死0612 18 24 30 36 42 48 54 60 66缬沙坦组缬沙坦组氨氯地平氨氯地平HR=1.19;95%CI=1.02-1.38;P=0.02 Julius S et al.Lancet.June 2004;363.19CCBs vs.利尿剂利尿剂/阻滞剂阻滞剂:致死性与非致死性脑卒中致死性与非致死性脑卒中0123MIDAS/NICS/VHASSTOP2/CCBsNORDIL/Dilt
14、iazem INSIGHT/Nifedipine GITSALLHAT/AmlodipineELSA/Lacidipine CCBs without CONVINCE p=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
15、.07CCBs较好较好利尿剂利尿剂/阻滞剂较好阻滞剂较好利尿剂利尿剂/阻滞剂阻滞剂试验试验事件数事件数/研究对象人数研究对象人数异质性检异质性检验验 危险比危险比(95%可信区间可信区间)差别差别(SD)CCBsStaessen 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
16、)Total mortalityCV mortalityStroke mortalityAll CV eventsFatal and non-fatal strokeActive treatment(n=1253)Placebo better82442094596133107445Active treatment better-39-39-58-37-3882442094596133107445FEVER:主要终点事件主要终点事件Liu LS et al.J Hypertens 2005;23:2157-2172.Chinese Hypertension Intervention Effica
17、cy(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 12.5 mg/dPrimary endpoint:CV death,stroke and MI2y 4y3y1y0yClear recommendationsnIf no compelling indications or contraindications,simply start with CLASSIC(Amlodipine),with the possible replacement of or combination with FASHION(ARB/ACEI).nThe A+A partnership.Thank you very much Thank you very much!