VALUE研究.ppt

缬沙坦降压治疗对高血压患者心血管事件的长期评估试验,Valsartan Antihypertensive Long-Term Use Evaluation,对于心血管高危的高血压患者，在相同的血压控制水平下，缬沙坦较氨氯地平更有效的降低心源性死亡率和发病率,VALUE: 主要假设,Julius S et al. Lancet. June 2004;363.,VALUE: 主要终点,主要终点包括: 心源性猝死 致死/非致死性急性心梗 尸检发现近期急性心梗证据 需要紧急溶栓 /PTCA或CABG以避免心肌梗死 PTCA或CABG术中或术后死亡 新发或慢性充血性心力衰竭需住院治疗 心衰死亡,Mann J, Julius S. Blood Press. 1998;7:176183.,VALUE: 次要终点及 预先设定的分析,次要终点: 致死或非致死性心梗 致死或非致死性脑卒中 致死或非致死性心力衰竭 预先设定的分析: 所有原因导致的死亡 新发糖尿病,Julius S et al. Lancet. June 2004;363.,VALUE: 试验设计 根据患者的情况递增剂量，直至达到目标血压140/90 mmHg,月 0.5 0 1 2 3 4 6 * 72,A 10 mg + HCTZ 25 mg,A 5 mg,A 10 mg + HCTZ 12.5 mg,A 10 mg,V 80 mg,V 160 mg,V 160 mg + HCTZ 12.5 mg,V 160 mg + HCTZ 25 mg,以氨氯地平为基础的治疗方案,V 160 mg + HCTZ 25 mg + 自由联用,A 10 mg + HCTZ 25 mg + 自由联用,以缬沙坦为基础的治疗方案,筛选,随机分组,治疗调整期结束,从既往的治疗方案转换 (92.7%),*第672月患者每6月随访一次,Julius S et al. Lancet. June 2004;363.,VALUE: 入选患者,治疗或未治疗的高血压患者* 年龄 50岁的男性或女性 心脏事件高危险 一项或更多确定的危险因素或疾病,Mann J, Julius S. Blood Press. 1998;7:176183. *未治疗高血压患者的入选标准:收缩压160210 mmHg，舒张压 95105 mmHg,VALUE: 患者特点,Patients (%),危险因素,疾病,33.3,22.5,31.6,24.0,12.2,3.6,45.8,19.8,13.9,6.1,Patients (%),VALUE结果: 络活喜降压疗效优于新型ARB -SBP,Julius S et al. Lancet. June 2004;363.,Valsartan (N= 7649),Amlodipine (N = 7596),135,140,145,150,155,mmHg,Months,不同时间和治疗组坐位 SBP,Baseline,1,24,48,2,3,4,6,12,18,30,36,42,54,60,66,0,1.0,2.0,3.0,4.0,1,24,48,mmHg,2,3,4,6,12,18,30,36,42,54,60,66,Months,5.0,缬沙坦和氨氯地平两组SBP差,1.0,(或终末随访),(或终末随访),VALUE:络活喜降压疗效优于新型ARB DBP,Julius S et al. Lancet. June 2004;363.,Valsartan (N= 7649),Amlodipine (N = 7596),mmHg,Months,不同时间和治疗组坐位 DBP,mmHg,Baseline,1,24,48,2,3,4,6,12,18,30,36,42,54,60,66,75,85,80,90,0,1.0,2.0,1,24,48,2,3,4,6,12,18,30,36,42,54,60,66,Months,3.0,缬沙坦和氨氯地平两组DBP差,1.0,4.0,5.0,(或终末随访),(或终末随访),VALUE: 试验结束时血压控制情况,56%,DBP (90 mmHg),88%,58%,SBP (140 mmHg),缬沙坦 为基础的治疗方案,Both SBP (140 mmHg) and DBP (90 mmHg),62%,92%,64%,Julius S et al. Lancet. June 2004;363.,氨氯地平 为基础的治疗方案,VALUE:主要终点(心脏病事件),14 12 10 8 6 4 2 0,Time (months),0 6 12 18 24 30 36 42 48 54 60 66,Proportion of Patients With First Event (%),Valsartan-based regimen,Amlodipine-based regimen,HR = 1.03; 95% CI = 0.941.14; P = 0.49,Julius S et al. Lancet. June 2004;363.,Number at risk,Valsartan,Amlodipine,7596,7649,7469,7459,7424,7407,7267,7250,7117,7085,6772,6732,6955,6906,6576,6536,5959,5911,3725,3765,1474,1474,6391,6349,Time (months),Number at risk,Valsartan,Amlodipine,7596,7649,7497,7499,7458,7458,7332,7319,7205,7177,6905,6853,7065,7016,6727,6680,6141,6078,3840,3864,1532,1520,6562,6504,Proportion of Patients With First Event (%),7 6 5 4 3 2 1 0,VALUE: 致死及非致死心肌梗死,0 6 12 18 24 30 36 42 48 54 60 66,缬沙坦组,氨氯地平组,HR = 1.19; 95% CI = 1.02-1.38; P = 0.02,Julius S et al. Lancet. June 2004;363.,19,VALUE:致死和非致死性脑卒中,Julius S et al. Lancet. June 2004;363.,Number at risk,Valsartan,Amlodipine,7596,7649,7499,7494,7455,7448,7334,7312,7195,7170,6918,6877,7055,7022,6744,6692,6163,6093,3846,3859,1532,1516,6587,6515,6 5 4 3 2 1 0,Time (months),0 6 12 18 24 30 36 42 48 54 60 66,Proportion of Patients With First Event (%),Valsartan-based regimen,Amlodipine-based regimen,HR = 1.15; 95% CI = 0.981.35; P = 0.08,15,VALUE: 不同时间段的血压与主要终点,Time Interval,(months),Overall study,3648,2436,1224,612,03,Study end,有利于氨氯地平,1.0,2.0,0.5,PRIMARY ENDPOINT Odds Ratios and 95% CIs,D,SBP,mmHg,1.4,1.6,1.8,2.0,3.8,1.7,2.2,36,2.3,有利于缬沙坦,4.0,Julius S et al. Lancet. June 2004;363.,VALUE: 不同时间段的收缩压与心梗,Julius S et al. Lancet. June 2004;363.,Time Interval,(months),Overall study,Study end,1.0,2.0,0.5,Myocardial Infarction Odds Ratios and 95% CIs,D,SBP,(mmHg),1.4,1.6,1.8,2.0,3.8,1.7,2.2,2.3,4.0,0.25,3648,2436,1224,612,03,36,有利于氨氯地平,有利于缬沙坦,VALUE: 耐受性,*With an incidence 3% and a difference between treatment groups 1%.,P 值,(%),(%),0.045,0.0001,0.0001,0.0001,2.0,2.4,房颤,1.0,1.7,晕厥,6.2,3.5,低钾血症*,Prespecified adverse events,6.4,9.3,心绞痛*,3.1,4.4,严重心绞痛,6.1,3.2,其它水肿*,6.8,8.8,腹泻*,Additional common adverse events,14.5,13.4,12.9,15.2,头痛,14.3,16.5,头晕,32.9,14.9,外周水肿,氨氯地平,缬沙坦,因不良事件退出试验,0.0001,0.0001,0.0001,0.1197,0.0001,0.0001,0.0001,VALU