VALUE研究

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ValsartanAntihypertensiveLong-TermUseEvaluation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JuliusSetal.Lancet.June2004;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MannJ,JuliusS.BloodPress.1998;7:176–183.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JuliusSetal.Lancet.June2004;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140/90mmHg月0.5012346*72A10mg+HCTZ25mgA5mgA10mg+HCTZ12.5mgA10mgV80mgV160mgV160mg+HCTZ12.5mgV160mg+HCTZ25mg以氨氯地平为基础的治疗方案V160mg+HCTZ25mg+自由联用A10mg+HCTZ25mg+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6–72月患者每6月随访一次JuliusSetal.Lancet.June2004;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MannJ,JuliusS.BloodPress.1998;7:176–183.*未治疗高血压患者的入选标准:收缩压160–210mmHg，舒张压95–105mmHgKjeldsenSE,JuliusSetal.BloodPress.2001;10:83–91.VALUE:患者特点Patients(%)危险因素疾病010203040血清肌酐升高左室肥厚蛋白尿吸烟糖尿病高胆固醇01020304050左室肥厚外周动脉病脑卒中冠脉疾病33.322.531.624.012.23.645.819.813.96.1Patients(%)VALUE结果:络活喜降压疗效优于新型ARB--SBPJuliusSetal.Lancet.June2004;363.Valsartan(N=7649)Amlodipine(N=7596)135140145150155mmHgMonths不同时间和治疗组坐位SBPBaseline124482346121830364254606601.02.03.04.012448mmHg23461218303642546066Months5.0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－DBPJuliusSetal.Lancet.June2004;363.Valsartan(N=7649)Amlodipine(N=7596)mmHgMonths不同时间和治疗组坐位DBPmmHgBaseline12448234612183036425460667585809001.02.01244823461218303642546066Months3.0缬沙坦和氨氯地平两组DBP差–1.04.05.0(或终末随访)(或终末随访)VALUE:试验结束时血压控制情况56%DBP(90mmHg)88%58%SBP(140mmHg)缬沙坦为基础的治疗方案BothSBP(140mmHg)andDBP(90mmHg)62%92%64%JuliusSetal.Lancet.June2004;363.氨氯地平为基础的治疗方案VALUE:主要终点(心脏病事件)14121086420Time(months)0612182430364248546066ProportionofPatientsWithFirstEvent(%)Valsartan-basedregimenAmlodipine-basedregimenHR=1.03;95%CI=0.94–1.14;P=0.49JuliusSetal.Lancet.June2004;363.NumberatriskValsartanAmlodipine759676497469745974247407726772507117708567726732695569066576653659595911372537651474147463916349Time(months)NumberatriskValsartanAmlodipine759676497497749974587458733273197205717769056853706570166727668061416078384038641532152065626504ProportionofPatientsWithFirstEvent(%)76543210VALUE:致死及非致死心肌梗死0612182430364248546066缬沙坦组氨氯地平组HR=1.19;95%CI=1.02-1.38;P=0.02JuliusSetal.Lancet.June2004;363.19％VALUE:致死和非致死性脑卒中JuliusSetal.Lancet.June2004;363.NumberatriskValsartanAmlodipine7596764974997494745574487334731271957170691868777055702267446692616360933846385915321516658765156543210Time(months)0612182430364248546066ProportionofPatientsWithFirstEvent(%)Valsartan-basedregimenAmlodipine-basedregimenHR=1.15;95%CI=0.98–1.35;P=0.0815％VALUE:不同时间段的血压与主要终点TimeInterval(months)Overallstudy36–4824–3612–246–120–3Studyend有利于氨氯地平1.02.00.5PRIMARYENDPOINTOddsRatiosand95%CIsDSBPmmHg1.41.61.82.03.81.72.23–62.3有利于缬沙坦4.0JuliusSetal.Lancet.June2004;363.VALUE:不同时间段的收缩压与心梗JuliusSetal.Lancet.June2004;363.TimeInterval(months)OverallstudyStudyend1.02.00.5MyocardialInfarctionOddsRatiosand95%CIsDSBP(mmHg)1.41.61.82.03.81.72.22.34.00.2536–4824–3612–246–120–33–6有利于氨氯地平有利于缬沙坦VALUE:耐受性*Withanincidence3%andadifferencebetweentreatmentgroups1%.P值(%)(%)0.0450.00010.00010.00012.02.4房颤†1.01.7晕厥†6.23.5低钾血症*Prespecifiedadverseevents6.49.3心绞痛*3.14.4严重心绞痛†6.13.2其它水肿*6.88.8腹泻*Additionalcommonadverseevents14.513.412.915.2头痛14.316.5头晕32.914.9外周水肿氨氯地平缬沙坦因不良事件退出试验0.00010.00010.00010.11970.00010.00010.0001VALUE:结论高危高血压患者及早积极控制血压至关重要JuliusSetal.Lancet.June2004;363.“这些发现提示控制BP达到推荐的目标应在相对短的时间内实现（数周而非数月），至少对于高危高血压患者应如此。”－－Julius,VALUE研究小组VALUE研究再次强有力的证明降压是减少心血管事件的根本，降压外作用的益处仍然缺乏证据应把降压达标能力作为药物选择的主要标准谢谢！