慢性心衰治疗研究的新进展课件

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level,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,慢性心衰治疗研究的新进展,主要内容,慢性心衰治疗的药物,醛固酮拮抗剂扩大了应用范围,减慢心率成为慢性心衰治疗的新靶标,心脏再同步化适用人群扩大,中药治疗心衰的临床研究已经启动,J Gen Physiol. 2002;120:1-13.,关闭,开放,抑制,Na,+,K,+,I,f,通道,伊伐布雷定单纯减慢心率的作用机制,0 mV,-40 mV,-70 mV,伊伐布雷定降低窦房结,4,期,动作电位自发除极曲线的斜率,Br J Pharmacol. 1994 May;112(1):37-42.,伊伐布雷定,单纯减慢心率,细胞外,细胞内,窦房结细胞,SHIFT试验的临床意义,证实伊伐布雷定治疗心衰有效,证实降低心率对心衰患者有益,降低心率成为慢性心衰治疗的新靶标,降低心率也可能成为心血管疾病治疗的新靶标,2012ESC心衰指南对伊伐布雷定的推荐,1.,即使已应用循证剂量的受体阻滞剂,ACEI/,或,ARB,，以及醛固酮拮抗剂，仍应考虑使用伊伐布雷定，以降低因心衰住院的风险,(a B),。,2.,心率,70,次,/,分,，,且不耐受受体阻滞剂的患者可考虑使用伊伐布雷定，以降低因心衰住院的风险。患者同时应接受,ACEI (,或,ARB),和醛固酮拮抗剂治疗,(IIb C),。,CRT 3,项临床研究（,2009-2010年,） ：,评估对,NYHA,级患者疗效,REVERSE,试验,：主要终点为中性，二级终点为阳性，表明,CRT,可改善此类患者的症状和生活质量,MADIT-CRT,试验：,主要终点和二级终点均为阳性：死亡和因心衰住院风险显著降低,34%,RAFT,试验：,阳性结果，表明患者可获益。,慢性心衰,CRT/ CRT-D,适用于：,标准和优化、强化治疗后,1. NYHA,-,级和,级,2.,心室显著不同步,3. LVEF,35,4.,窦性节律,2012ESC指南：,收缩性心衰的非药物器械治疗,-CRT,：,适用于窦性心律、经标准和优化抗心衰治疗,LVEF,仍持久降低，预期生存期,1,年患者，且,1.,心功能,-,级，伴,LBBB(,，,A),，,或不伴,LBBB,，但,QRS,130ms,。,2.,心功能级，伴,LBBB(,，,A),，,或不伴,LBBB,，但,QRS,150ms,。,2012ESC指南：,收缩性心衰的非药物器械治疗,-CRT,：,下列,2,种状况患者,CRT,能否获益则尚不确定：,(1),伴房颤的患者,(2)LVEF,降低，并有作常规心脏起搏的指征，但并无作,CRT,的其他适应证。,舒张性心衰心衰,的诊断,1.,典型的心衰症状，,2.,典型的心衰体征，,3. LVEF,正常或仅轻度降低，且左心室未扩大，,4.,存结构性心脏病,(,如左室肥厚、左房增大,),和,/,或舒张性心功能障碍。,慢性收缩性心衰的药物治疗,推荐应用于所有心功能,-,级,1.,血管紧张素转化酶抑制剂,(ACEI) (,，,A),2.,受体阻滞剂,(,，,A),3.,醛固酮拮抗剂,(,，,A),4. 血管紧张素受体阻滞剂,（,ARB,）,(,A),5.,伊伐布雷定,用耒降低因心衰再住院率,(,a,，,B),，,替代用于不能耐受受体阻滞剂的患者,(,b,，,C),推荐应用于所有心功能,-,级,可改善症状并可长期应用,1.,地高辛,(,b,，,B),2.,利尿剂,（, ,C,）,对慢性心衰病死率和发病率的影响并未作过临床研究，但可以减轻气促和水肿，推荐用于有心衰症状和体征，尤其伴显著液体滞留的患者。,推荐应用于所有心功能,-,级,其他可考虑的药物：,1.,肼苯达嗪和硝酸酯类联用,(,b,，,B),2. n-3PUFA(,b,，,B),。,慢性收缩性心衰的药物治疗,未证实有益而不推荐应用的药物,：,他汀类,肾素抑制剂,(,阿利吉伦,),口服抗凝药。,可能有害而不予推荐的药物：,1.,噻唑烷类降糖药,：,可使心衰恶化。,2.,大多数鈣拮抗剂,：,有负性肌力作用，使心衰恶化。氨氯地平和非洛地平除外，必要时可用。,3.,非甾体类抗炎剂,(NSAIDs),和,COX-2,抑制剂,可导致水鈉滞留，使心衰恶化，并损害肾功能,4,. ACEI,和醛固酮拮抗剂合用基础上加,ARB,：,这,3,种药合用会增加肾功能损害和高钾血症的风险。,慢性心衰新的处理方案,主要应用的药物：,利尿剂,ACEI ARB,醛固酮拮抗剂,阻滞剂 地高辛,伊伐布雷定,基本或标准方案,利尿剂 ,ACEI,阻滞剂 ,伊伐布雷定,慢性心衰新的处理方案,优化的治疗方案：,利尿剂,： 使液体滞留消失，处“干重”状态,ACEI,：,达目标剂量或最大耐受剂量,阻滞剂,： 达目标剂量或最大耐受剂量,伊伐布雷定,： 适用于不能应用,阻滞剂，或不能用至目标剂量（或最大耐受剂量）的患者,强化治疗方案,基本和优化治疗基础上加用：,醛固酮拮抗剂：,NYHA,-,级和,级,伊伐布雷定 ： 使心率降至,65,次,/,分,地高辛 （,a，B,),：,NYHA,级,ARB (b ，B) ： NYHA-,级,主要内容,慢性心衰治疗的药物,醛固酮拮抗剂扩大了应用范围,减慢心率成为慢性心衰治疗的新靶标,心脏再同步化适用人群扩大,中药治疗心衰的临床研究已经启动,芪苈强心胶囊治疗慢性心衰有效性与安全性,随机、双盲、安慰剂平行对照多中心临床试验,中国循证医学注册中心注册号：,ChiCTR-TRC-11001478,主要研究者：,中国医学科学院阜外心血管病医院,高润霖 院士,中国中医科学院,张伯礼 院士,南京医科大学第一附属医院,中华医学会心血管病学分会心衰学组,黄峻 教授,试验组织者：石家庄以岭药业股份有限公司,试验计划开始日期：,2011,年,06,月,学术委员会,高润霖、张伯礼、黄,峻,马爱群,、,杨杰孚、吴宗贵、韩雅玲、李为民,李新立、张,健、姚,晨,中华医学会心血管病分会心衰学组,主要研究单位,主持单位：国家心血管病中心，阜外医院,南京医科大学第一附属医院,参与单位：,全国18家大医院,研究前评估和设计耗时,2年半时间,试验目的,以血清,NT-proBNP,作为替代终点，主要评价中药芪苈强心胶囊对慢性心衰患者血清,NT-proBNP,的影响,评价芪苈强心胶囊对慢性心衰患者生活质量等指标,评价芪苈强心胶囊,的,有效性及安全性，为慢性心衰的中西医结合治疗提供临床依据。,研究依据,芪苈强心胶囊药理学实验,(,心衰动物模型,),证明,：,明显改善血流动力学指标,显著增加左室心肌收缩力,显著升高左室内压峰值及左室内压最大上升速率,明显降低左室舒张末期压，增加心输出量,扩张外周血管，增加肾血流量，具有明显利尿效果,明显降低血清血管紧张素，抑制血清醛固酮含量的增加,明显改善室壁厚度及全心质量指数,具有抑制心室重塑的作用,。,研究依据,芪苈强心胶囊,II,、,III,期临床试验证实,：,芪苈强心胶囊可明显改善冠心病、高血压病所致慢性心衰患者心功能分级,提高射血分数和,E/A,比值，改善临床症状,改善,明尼苏达心衰生活质量量表评分,增强了患者的心功能，提高了患者的生活质量,研究终点,主要有效性终点,NT-proBNP,（中心实验室）：试验组相对疗前的下降率优于对照组,，,或试验组相对疗前下降超过,30%,的比例优于对照组,次要有效性终点,两组血清,NT-proBNP,含量相对疗前下降值的比较,明尼苏达生活质量量表,NYHA,心功能分级；超声心动图：左室舒张末期内径,(LVED),；左室射血分数,(LVEF),6min,步行距离试验,(6MWT),合并用药,1.,接受控制高血压、心绞痛、糖尿病或其他疾病的药物治疗,2.,入选前停用任何中药或中成药,1,个月以上，进入随机分组阶段之后整个治疗期均不得使用研究药物以外的其他与试验药物成分类似中药。,3.,患者接受有利于心脏健康的饮食指导，如低盐饮食，适量饮水等，同时接受诸如监测体重、体育锻炼、戒烟、戒酒等适当生活方式改善的咨,询,4.,目前尚未发现禁止与芪苈强心胶囊伴随使用的药物,疗程：,12,周,研究现状,研究已完成,一周前举行了揭盲前评估会，对试验运行质量予以肯定,研究结果将在本月底第,4届,全国心衰大会上发表,本月,23日将举行电视会向全国发布研究结果,益气活血经典代表,国家中药保护品种,国家医疗保险乙类目录产品,唯一通过国际标准循证医学验证的现代中药产品,芪参益气滴丸,多效改善心功能,老年冠心病首选治疗中药,芪参益气滴丸组方分析,黄芪：方中重用黄芪，取其大补元气，使气旺以促血行，祛瘀而不伤正；气旺以促津行，行津利尿，则水肿自消，黄芪帅诸药之力，为君药。,丹参：活血祛瘀，通经止痛，与三七共为臣药。,三七：活血止血，双向调节血液凝聚性，与丹参共为臣药。,降香油：气香辛散，温通行滞，用作使药。,诸药合用益气活血，利水消肿，通络止痛，得以气血运行正常，诸证自愈。,尤其适合,65,岁以上老年患者及三年以上病程的冠心病患者使用。,芪参益气滴丸在慢性心衰治疗中的应用,一些小样本的研究发现：在基础治疗中加用芪参益气滴丸，可以在六分钟步行试验的改善及心脏彩超指标方面收到良好的效果。,现在已经启动的一项国家中医药科研专项研究，计划观察冠心衰病例,640,例，联合,35,家大型医院，采用随机双盲方法，以期获得在这面的权威数据。,芪参益气滴丸治疗冠心病心力衰竭有效,实用心脑肺血管病杂志,2010,年,3,月第,18,卷第,3,期,结果：两组患者用药前六分钟步行试验比较差异无统计学意义,(P0.05);,用药,1,、,2,周后两组患者六分钟步行试验比较差异均有统计学意义,(P 0.05),。,结论：认为芪参益气滴丸是治疗冠心病心力衰竭安全、有效的辅助用药。,两组患者用药前与用药后六分钟步行试验比较（,S,，,m,）,组别 例数 用药前 用药后一周 用药后两周,治疗组,64 158.0023.12 310.0028.23 460.0036.11,对照组,64 162.0025.18 301.0021.17 442.0031.19,山东医药,2008,年第,48,卷第,28,期,-47-,芪参益气滴丸治疗老年充血性心力衰竭有效,两组治疗前后心功能指标比较（,S,，,m,）,组别,n CO(L/min) CI L/(minm,2,) EF(%),治疗组,30,治疗前,3.810.92 2.100.52 0.380.13,治疗后,5.680.78 3.140.38 0.590.08,对照组,28,治疗前,3.820.86 2.120.51 0.400.12,治疗后,4.580.85 2.540.48 0.500.10,注：与同组治疗前比较，,* P0.01,，与对照组治疗后比较，,P0.05,*,*,*,*,*,*,未来研究动态,拟进行临床试验，科学评估其对慢性心衰治疗的临床疗效,各项相关工作正在研讨评估之中,小结,慢性心衰有效的治疗药物从,6种增加至7种，增加了伊伐布雷定,醛固酮拮抗剂扩大了应用范围,减慢心率成为慢性心衰治疗的新靶标,心脏再同步化适用人群扩大,中药治疗慢性心衰的研究已经展开。芪苈强心胶囊，芪参益气滴丸已先行一步。,谢 谢！,结束语,谢谢大家聆听！,43,