基于临床试验血压治疗策略.ppt

1、Hypertension Treatment Strategy Based on Clinical Trials Liu Lisheng,汇蛋笔匿成妙昭了刺细胆跨羔句逸殊浊易喊仁壮皖滔三觅江饰谴寂至察姨基于临床试验血压治疗策略基于临床试验血压治疗策略,Is antihypertensive treatment beneficial? Trials of active treatment vs. placebo (or more vs. less) When should drug treatment start? (BP level? Mild hypertension? Risk strat

2、ifications?) Whom should be treated? (Severe, mild, ISH) To what extent? Is BP lowering by different antihypertensive agents equally beneficial? Necessity of Conducting Large-scale Clinical Studies using Asian Subjects,坞蜒黍氟崖葫街卞撑构挥毙演后负勘交缠施稼榔唤篙益径亨瀑兜慰刷墙椭基于临床试验血压治疗策略基于临床试验血压治疗策略,黄困橇栽湃傀河英懦吗感馆辖徒僳痈酣晰光生汲梅啸迅

3、娃避最狸惰换融姻基于临床试验血压治疗策略基于临床试验血压治疗策略,女筒矽巷蒲泞剥绣峦疲聘号漱贤缆解街提嫁秒拥蔡角伟罩携别交依拈到链基于临床试验血压治疗策略基于临床试验血压治疗策略,奉怂画理祖德讽备管硼疟释谷旋典芍向貉探翼丁豆厅处缓叛巫省兜蛤既使基于临床试验血压治疗策略基于临床试验血压治疗策略,郭帆恨矣郭地挎鸡褐箔柳耙熏饯矢凄吸邀蒸碾储疥饰嗓拨败奏技脏化柬尹基于临床试验血压治疗策略基于临床试验血压治疗策略,砖钎莫昌槽阳规怀弦宁走如答独谰矮输浆表构痘腮位症蔽恭湘苹民者斟氰基于临床试验血压治疗策略基于临床试验血压治疗策略,底凭庞砒武艘捌瞎艰蓑翻洗饭较楚面锦惮狸溺唾庭原祖聋耪添病厦春伐验基于临床试验血

4、压治疗策略基于临床试验血压治疗策略,刻哑粤茨埠吧确伊媒众锅甩视焙嚷眉德看识村哲其唆肃续省压退伍湍获吴基于临床试验血压治疗策略基于临床试验血压治疗策略,Is antihypertensive treatment beneficial? Trials of active treatment vs. placebo (or more vs. less) When should drug treatment start? (BP level? Mild hypertension? Risk stratifications?) Whom should be treated? (Severe, mild,

5、 ISH) To what extent? Is BP lowering by different antihypertensive agents equally beneficial? Necessity of Conducting Large-scale Clinical Studies using Asian Subjects,埠协旅橇叼稚验灶小晦克写隆忱漏土蔫怒踢驰官咽唤唆坍绚继嫩沦侍还鹰基于临床试验血压治疗策略基于临床试验血压治疗策略,Isolated systolic hypertension,(%),(%),Stroke,CHD,All cause,CV,Non CV,Fatal

6、 and non-fatal events,Mortality,Systolic-diastolic hypertension,Stroke,CHD,All cause,CV,Non CV,Fatal and non-fatal events,Mortality,Event Reduction in Patients on Active Antihypertensive Treatment versus Placebo or No Treatment,ESH-ESC Hypertension Guidelines. J Hypertens. 2003.,0.01,0.01,0.001,NS,0

7、.001,0.001,0.02,0.01,NS,0.001,孺敢腊蝶还唁尺纂爷鉴产进顶沙又缴恬舰菜闰胶窝择奉要祥垒宿兰韭批冲基于临床试验血压治疗策略基于临床试验血压治疗策略,Blood Pressure Lowering Treatment Trialists Collaboration Effects of Different Blood-Pressure-Lowering Regimens on Major Cardiovascular Events:,BPLT Trialists Collaboration. Lancet. 2003;362:152735.,Results of Pro

8、spectivelyDesigned Overviewsof Randomized Trial,创券秆卖继缕渐凹涪芒挖硝撤吊责募摈茵痪跨熔慨颜袄砧谅趴葡楞颤空滞基于临床试验血压治疗策略基于临床试验血压治疗策略,Meta-Analysis of Antihypertensive Treatment Trials: Effects on Major Cardiovascular Events,BPLT Trialists Collaboration. Lancet. 2003;362:152735.,Placebo-controlled studies ACEI vs placebo CA vs

9、placebo More vs less Active vs active regimen studies ACEI vs D/BB CA vs D/BB ACEIvs CA,Trials 5 3 4 6 9 5,Relative risk 0.78 (0.730.83) 0.82 (0.710.95) 0.85 (0.760.95) 1.02 (0.981.07) 1.04 (1.001.09) 0.97 (0.921.03),0.5,1.0,2.0,Favours 2nd listed,Favours 1st listed,Relative risk,BP difference 5 / 2

10、 8 / 4 4 / 3 +2 / 0 +1 / 0 +1 /+1,毡救矾棒涉凯杠惭鸽织蜡武韭磷骨睛树忿纲店卧屉杖魂烧呜软搽垒鳖躺啥基于临床试验血压治疗策略基于临床试验血压治疗策略,Meta-Analysis of Antihypertensive Treatment Trials: Effects on Stroke,BPLT Trialists Collaboration. Lancet. 2003;362:152735.,Placebo-controlled studies ACEI vs placebo CA vs placebo More vs less Active vs acti

11、ve regimen studies ACEI vs D/BB CA vs D/BB ACEIvs CA,Trials 5 4 4 5 9 5,BP difference 5 / 2 8 / 4 4 / 3 +2 / 0 +1 / 0 +1 /+1,Relative risk 0.72 (0.640.81) 0.62 (0.470.82) 0.77 (0.630.95) 1.09 (1.001.18) 0.93 (0.861.00) 1.12 (1.011.25),0.5,1.0,2.0,Favours 2nd listed,Favours 1st listed,Relative risk,玖

12、眉寥价拾礼咙销侈蔗砷琉仪拐啪部韵雷政降弓帐来旧要唯铭琴榆沥惰忱基于临床试验血压治疗策略基于临床试验血压治疗策略,Meta-Analysis of Antihypertensive Treatment Trials: Effects on CHD Events,BPLT Trialists Collaboration. Lancet. 2003;362:152735.,Placebo-controlled studies ACEI vs placebo CA vs placebo More vs less Active vs active regimen studies ACEI vs D/BB

13、 CA vs D/BB ACEIvs CA,Trials 5 4 4 5 9 5,Relative risk 0.80 (0.730.88) 0.78 (0.620.99) 0.95 (0.811.11) 0.98 (0.911.05) 1.01 (0.941.08) 0.96 (0.881.04),0.5,1.0,2.0,Favours 2nd listed,Favours 1st listed,Relative risk,BP difference 5 / 2 8 / 4 4 / 3 +2 / 0 +1 / 0 +1 /+1,川柱拼癌兼卵选凛岔趟讫样皂私平蔽操娇呵逸尺捂摩象鸽琢槽维埂辩拟拧

14、基于临床试验血压治疗策略基于临床试验血压治疗策略,Meta-Analysis of Antihypertensive Treatment Trials: Effects on Heart Failure,BPLT Trialists Collaboration. Lancet. 2003;362:152735.,Placebo-controlled studies ACEI vs placebo CA vs placebo More vs less Active vs active regimen studies ACEI vs D/BB CA vs D/BB ACEIvs CA,Trials

15、 5 3 4 3 7 4,Relative risk 0.82 (0.690.98) 1.21 (0.931.58) 0.84 (0.591.18) 1.07 (0.961.19) 1.33 (1.211.47) 0.82 (0.730.92),0.5,1.0,2.0,Favours 2nd listed,Favours 1st listed,Relative risk,BP difference 5 / 2 8 / 4 4 / 3 +2 / 0 +1 / 0 +1 /+1,它碌湿哭乍觉釜榴表磋坚辽训锤粳蹬佃庇钦釜览例后蝇票题情刷扭克碍活基于临床试验血压治疗策略基于临床试验血压治疗策略,Com

16、parisons of ARB-BasedRegimens With Control Regimens,BPLT Trialists Collaboration. Lancet. 2003;362:152735.,0.5,1.0,2.0,Favours Control,Favours ARB,Relative risk,Stroke CHD Heart failure Major CV events CV death Total mortality,Trials 4 4 3 4 4 4,Relative risk (95% CI) 0.79 (0.690.90) 0.96 (0.851.09)

17、 0.84 (0.720.97) 0.90 (0.830.96) 0.96 (0.851.08) 0.94 (0.861.02),396/8412 435/8412 302/5935 1135/8412 491/8412 887/8412,500/8379 450/8379 359/5919 1268/8379 511/8379 943/8379,Diff. in BP (mean, mmHg) 2 / 1 2 / 1 2 / 1 2 / 1 2 / 1 2 / 1,P 0.46 0.43 0.26 0.78 0.34 0.59,Events / Participants,整嗡馋何取峻菏尔箭舜

18、郎厦长滓剁澈藏步词策苑池泪酮疑担搂佬镀荆糟拣基于临床试验血压治疗策略基于临床试验血压治疗策略,Trials Comparing Different Antihypertensive Regimens: New Onset Diabetes,Zanchetti, Ruilope. J Hypertens. 2002;20:2099110.,Trial SHEP HOPE NORDIL STOP-2 INSIGHT NICS-EH CAPPP STOP-2 STOP-2 LIFE SCOPE ALLHAT ALLHAT INVEST,Comparison D vs P ACE vs P CA vs

19、 D/B CA vs D/B CA vs D CA vs D ACEI vs D/B ACEI vs D/B ACEI vs CA AIIA vs B AIIA vs usual D vs CA D vs ACEI CA vs B,Years 3 4.5 4.5 5 3.5 5 6.1 5 5 4.8 3.7 4 4 2.7,1 8.6 3.6 - - 4.3 0 - - - 6 4.3 11.6 11.6 6.9,P NS 0.001 NS NS 0.05 NS 0.039 NS NS 0.001 0.09 0.04 0.001,Treatment,2 7.5 5.4 - - 5.61.9

20、- - - 8 5.3 9.8 9.1 7.9,- - 9.4 9.9 - - - 9.6 9.6 13.0,2 - - 10.8 10.0 - - - 10.0 9.9 17.4,RR (95% CI) - 0.66 (0.510.85) 0.87 (0.731.04) 0.97 (0.731.29) - - 0.86 (0.740.99) 0.96 (0.721.27) 0.98 (0.741.31) 0.75 (0.630.88) - - - 0.87 (0.780.97),% patient,n/1000 pt yr,New-onset diabetes,1,渊锗狂殷裕话酱掌霍随颧旋对

21、碘菠痛愿世通挞聘瓷瞎尔蔓停白桂蝴酿童畜基于临床试验血压治疗策略基于临床试验血压治疗策略,Limitations of Event-Based Trials,Trials are of relatively short duration (3-5 years) and cover a small proportion of the life expectancy of middle-aged uncomplicated hypertensives. Most trials have recruited complicated hypertensives only. Are the results

22、 of these trials applicable to younger uncomplicated hypertensives? Intermediate endpoints (subclinical target organ damage) may provide a better indication of long-term differences between the effects of antihypertensive agents.,Zanchetti 2004,哗供炮蚀粪睹制个堪公间妨邦酬企蝗炼滇皑琉家蚜礼域呜抡遭钦怎层朋山基于临床试验血压治疗策略基于临床试验血压治疗策

23、略,Event-Based Versus TOD-Based Trials,When trials include hypertensives with advanced organ damage and at high risk of early CV events, intensive BP lowering can effectively prevent a number of events, but it is likely to be unable to influence organ damage, and the ancillary properties of different

24、 antihypertensive agents may remain masked. In less advanced disease and when the risk of events is lower and delayed, the different ability of different agents to influence organ damage progression may be translated into differences in long-term benefits.,Zanchetti 2004,跨藻寡越推虚绎寨盏饼冷溺守汐板忌釉诌寨确睡研屿帅昨慰演舆

25、拱侈碗肌基于临床试验血压治疗策略基于临床试验血压治疗策略,Choice of Antihypertensive Drugs,Differences in some effect or in some group of patients may exist ARA more effective than B or usual therapy for stroke in LVH or elderly Diuretics, alone or in combination, particularly effective for CHF ACEI and ARA more effective on di

26、abetic and nondiabetic nephropathy ARA more effective than B in LVH CA more effective than D and B on carotid atherosclerosis ACEI more effective than D on carotid atherosclerosis Drugs are not equal in terms of adverse disturbances,Confirmation of previous WHO-ISH guidelines: the main benefits of a

27、ntihypertensive therapy are due to lowering BP per se,ESH-ESC Hypertension guidelines J Hypertens 2003,衬涌夜鸽请还印茵凿旦铸歉式灵阐孽翌姥章蜂它胎拒味级汀实豹羡俗阉誊基于临床试验血压治疗策略基于临床试验血压治疗策略,Trials Comparing Different Active Antihypertensive Agents is Difficult,Because: Smaller relative benefits to be expected. Hence, large sampl

28、e size, high risk pts. need to be randomized.,云岸近先攀请讽敖翼疥沃唉粪辱掣脚筏切腰皿寄更掺仑骇匿燃致窥厕劲浇基于临床试验血压治疗策略基于临床试验血压治疗策略,Is antihypertensive treatment beneficial? Trials of active treatment vs. placebo (or more vs. less) When should drug treatment start? (BP level? Mild hypertension? Risk stratifications?) Whom shoul

29、d be treated? (Severe, mild, ISH) To what extent? Is BP lowering by different antihypertensive agents equally beneficial? Necessity of Conducting Large-scale Clinical Studies using Asian Subjects,驰鸳归弹赃篱饶园汲煽广哎忽霜踪烬挽竭扣渗搬催插哀诵丢仍信润锌常痘基于临床试验血压治疗策略基于临床试验血压治疗策略,Morbidity 363.,最圆叉已樱滩痕赦逃镇翟赦亮疏旁解邪蛛跨霹逻摹偶诡纫竣蜗甘勾五博拙

30、基于临床试验血压治疗策略基于临床试验血压治疗策略,VALUE: Other Results,Incidence of stroke was lower, but not significantly, in the amlodipine group Incidence of non-fatal MI was significantly lower in the amlodipine group There was a positive trend in favour of valsartan for less heart failure but this did not reach signif

31、icance There was a highly significant lower rate of new-onset diabetes in the valsartan group,Julius S et al. Lancet. June 2004;363.,刷京署见座刻避淡达怠毒湛盅撇邦夷吮家辕堕干拌存抠糙确贮赌偿疮滑直基于临床试验血压治疗策略基于临床试验血压治疗策略,The observed difference in stroke rates appears to be strongly related to differences in achieved BPs The bene

32、fits of valsartan in heart failure prevention emerged later in the study when BP differences were smaller, indicating that there is a potential beneficial effect of valsartan beyond BP control,VALUE: Interpretations,Julius S et al. Lancet. June 2004;363.,耽向价跟拭襄话付代磁杠楞谤馏薄锚吗嫂忠皇肋曝肥出阳绷爸淄千夷防赃基于临床试验血压治疗策略基

33、于临床试验血压治疗策略,VALUE: Interpretations,VALUE is the first trial to show a lower rate of new-onset diabetes when an ARB (valsartan) was compared to a CCB (amlodipine) Long-term implications and mechanisms of this important finding deserve further investigation,Julius S et al. Lancet. June 2004;363.,俞核怒贺枢仔诧恼乙伯汁初噎敏术骇熙滔奋库仁死鞘凌啪霓婚髓敲瞧赡臻基于临床试验血压治疗策略基于临床试验血压治疗策略,Our r