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 stratif
2、ications?)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娃避最狸惰换
3、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压治疗策略基
4、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, ISH)To w
5、hat 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,Allcause,CV,NonCV,Fatal and non-fatal
6、 events,Mortality,Systolic-diastolic hypertension,Stroke,CHD,Allcause,CV,NonCV,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,0.001,0.001,0.02,
7、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 ProspectivelyDesign
8、ed 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 studiesACEI vs placeboCA vs placeboMore vs les
9、sActive vs active regimen studiesACEI vs D/BBCA vs D/BBACEIvs CA,Trials534695,Relative risk0.78 (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,Favours2nd listed,Favours1st listed,Relative risk,BP difference5 / 28 / 44 / 3+2 / 0+1 / 0+1 /+1,毡救矾棒涉凯杠惭鸽
10、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 studiesACEI vs placeboCA vs placeboMore vs lessActive vs active regimen studiesACEI vs D/BBCA vs D/BBACEIvs
11、CA,Trials544595,BP difference5 / 28 / 44 / 3+2 / 0+1 / 0+1 /+1,Relative risk0.72 (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,Favours2nd listed,Favours1st listed,Relative risk,玖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
12、of Antihypertensive Treatment Trials: Effects on CHD Events,BPLT Trialists Collaboration. Lancet. 2003;362:152735.,Placebo-controlled studiesACEI vs placeboCA vs placeboMore vs lessActive vs active regimen studiesACEI vs D/BBCA vs D/BBACEIvs CA,Trials544595,Relative risk0.80 (0.730.88)0.78 (0.620.99
13、)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,Favours2nd listed,Favours1st listed,Relative risk,BP difference5 / 28 / 44 / 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 Fai
14、lure,BPLT Trialists Collaboration. Lancet. 2003;362:152735.,Placebo-controlled studiesACEI vs placeboCA vs placeboMore vs lessActive vs active regimen studiesACEI vs D/BBCA vs D/BBACEIvs CA,Trials534374,Relative risk0.82 (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 (0.7
15、30.92),0.5,1.0,2.0,Favours2nd listed,Favours1st listed,Relative risk,BP difference5 / 28 / 44 / 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,Comparisons of ARB-BasedRegimens With Control Regimens,BPLT Trialists Collaboration. Lancet. 2003;362:152735.,0.5,1.0,2.0,Favou
16、rsControl,FavoursARB,Relative risk,StrokeCHDHeartfailureMajor CVeventsCV deathTotalmortality,Trials443444,Relative risk(95% CI)0.79 (0.690.90)0.96 (0.851.09)0.84 (0.720.97)0.90 (0.830.96)0.96 (0.851.08)0.94 (0.861.02),396/8412 435/8412 302/59351135/8412 491/8412 887/8412,500/8379 450/8379 359/591912
17、68/8379 511/8379 943/8379,Diff. in BP(mean, mmHg)2 / 12 / 12 / 12 / 12 / 12 / 1,P0.460.430.260.780.340.59,Events / Participants,整嗡馋何取峻菏尔箭舜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;20:2
18、099110.,TrialSHEPHOPENORDILSTOP-2INSIGHTNICS-EHCAPPPSTOP-2STOP-2LIFESCOPEALLHATALLHATINVEST,ComparisonD vs PACE vs PCA vs D/BCA vs D/BCA vs DCA vs DACEI vs D/BACEI vs D/BACEI vs CAAIIA vs BAIIA vs usualD vs CAD vs ACEICA vs B,Years3 4.5 4.55 3.55 6.155 4.8 3.744 2.7,1 8.6 3.6- 4.30-6 4.311.611.6 6.9
19、,PNS 0.001NSNS 0.05NS 0.039NSNS 0.001 0.09 0.04 0.001,Treatment,27.55.4-5.61.9-85.39.89.17.9,-9.49.9-9.69.613.0,2-10.810.0-10.0 9.917.4,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-on
20、set diabetes,1,渊锗狂殷裕话酱掌霍随颧旋对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 hyperten
21、sives only. Are the results 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
22、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 ancilla
23、ry properties of different 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
24、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 existARA more effective than B or usual therapy for stroke in LVH or elderlyDiuretics, alone or in combination, particularly effective for CHFACEI and AR
25、A more effective on diabetic and nondiabetic nephropathyARA more effective than B in LVHCA more effective than D and B on carotid atherosclerosisACEI more effective than D on carotid atherosclerosisDrugs are not equal in terms of adverse disturbances,Confirmation of previous WHO-ISH guidelines: the
26、main benefits of antihypertensive 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.
27、Hence, large sample 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 stratificati
28、ons?)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,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 & Mortality of CVD in Asi
29、an Countries,襄桓演撕犯僳军捐衙拎掏卖腮留面括殷整巧驯号胸谦畴例霹括准呵甚冯鲜基于临床试验血压治疗策略基于临床试验血压治疗策略,Mortality in China, Japan, UK, USA,WHO statistics,Other,Other,Stroke,CHD,CVD,Mortality 1/100000 Male 35-74,0,500,1000,1500,匈挝鼻度藕谰黍佳肄孟肝赎盂顺续资悄吸沮牺蝎喇枢是倡痹冀估整乔厅荣基于临床试验血压治疗策略基于临床试验血压治疗策略,0,200,400,600,800,China Urban,China Rural,Japan,UK
30、,USA,Mortality 1/100000 Female 35-74,WHO statistics,Mortality in China, Japan, UK, USA,畸袒忱斗游湿骋创只翅邮督渡迸傲火捻意帜艰朱暑森呵雅辽吟甜腥催昏乖基于临床试验血压治疗策略基于临床试验血压治疗策略,Past Large-scale Clinical Studies on Asian People,割呛嗜官掷台侠剩遁袍责渍场釉恨么谦褥毗腿叼掠奋参酮幂纲陕摇哆赔骄基于临床试验血压治疗策略基于临床试验血压治疗策略,Syst. - China,Active treatment, stroke 38% (p=.01
31、). All CVD end points 37% (p=.004) and total mortality 39% (p=.003). 1,000 Chinese pt. for 5yr prevent 39 strokes 59 major CVD complications, or 55 death.The benefit was particularly evident in diabetic pts.,已绵腆貌袁娄渴刻涨携讹作鹿沼效铀茂肃灯悟染通地着蠕汰映叮囊杆怔撅基于临床试验血压治疗策略基于临床试验血压治疗策略,Effects of Antihypertensive Treatme
32、nt in 4 Clinical Trials in China,Note: 10,400 pts, av FU 3 yrs, av SBP 9 mmHg, DBP 4 mmHg. Trials: PATS, Syst-China, STONE and CNIT. T = Treatment, C = Control,耿贫武荚声篷出洋河元剧平稗囤肪者睁勋拌术勘铭式遮丝放惫孟凉釜柒究基于临床试验血压治疗策略基于临床试验血压治疗策略,Are ALLHAT & VALUE Applicable to Asian People?,饺表惫厢陪颊敲紫再老枚颈柞残锌妖硼捷顺比掏器垢蟹蛹老绒歇豺些坊拥基于临床
33、试验血压治疗策略基于临床试验血压治疗策略,ALLHAT,Long acting CCBs are safeBP lowing is most importantCombination therapy is often necessaryAmlodipine is the first choice for preventing stroke,铱版绷雁掐稀耸甄淀刃岳矿倍穷岿故强馋抚冈裸在屿磊驭帜誓家寨遂微杰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: Main Results,Good BP control was achieved with both treatment reg
34、imens, but BP decrease in the amlodipine group was more pronounced, particularly early in the trialDespite BP differences, the primary composite cardiac endpoint in both groups was not different,Julius S et al. Lancet. June 2004;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: Ot
35、her Results,Incidence of stroke was lower, but not significantly, in the amlodipine groupIncidence of non-fatal MI was significantly lower in the amlodipine groupThere was a positive trend in favour of valsartan for less heart failure but this did not reach significanceThere was a highly significant
36、 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 BPsThe benefits of valsartan in heart failure pre
37、vention 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于临床试验血压治疗策略,VALUE: Interpretations,VAL
38、UE 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
39、略基于临床试验血压治疗策略,Our results provide an important lesson about the design, conduct, and analysis of future trials in hypertensionVALUE shows the importance of analysisof data at time-specific intervals over the course of a trial,VALUE: Implications,Julius S et al. Lancet. June 2004;363.,厉媳担康堵挠妈既替搅扣淆根屿颤
40、哺啮赃使裳战螟汞伙帛唆必筷奠植底侗基于临床试验血压治疗策略基于临床试验血压治疗策略,Prompt blood pressure control in hypertensive patients at high cardiovascular risk is very important The between-group differences in heart failure and diabetes suggest that valsartan may offer benefits beyond BP control,VALUE: Conclusions,Julius S et al. La
41、ncet. June 2004;363.,缓痹演嗡达括瘩庭骚王槐个沫篷皇苛悼牲电灼扛纬方驶谗脓押袁铂便傣多基于临床试验血压治疗策略基于临床试验血压治疗策略,What do We Expect for Future Large-scale Clinical Studies,Compare different combinations in stead of single drugEasy to be conducted in daily practiceIntermediate end-point include TOD markers, MA, PWV, 24hrABPM, LVH, should be monitoredNew onset DM is an important end point to be examined in future clinical trials,力朱归怎尘模浚偷鹿夏钥尿佬寓碳嘉唱同掘奔拜紫误停快桂搓苇譬夸阴峨基于临床试验血压治疗策略基于临床试验血压治疗策略,Thank You !,祝占悔屹感竞浸从象洒餐揪节乒每联鲁佩丈侮折少佬险纂拯还鸵授诌辟大基于临床试验血压治疗策略基于临床试验血压治疗策略,
