OCC 2020:黄峻教授:慢性心衰药物全新作用机制展露新曙光

2020-06-05 黄美清 健康界

心力衰竭(心衰)是多种原因导致心脏结构和/或功能的异常改变,使心室收缩和/或舒张功能发生障碍,从而引起的一组复杂临床综合征,主要表现为呼吸困难、疲乏和液体潴留(肺淤血、体循环淤血及外周水肿)等。根据左

心力衰竭(心衰)是多种原因导致心脏结构和/或功能的异常改变,使心室收缩和/或舒张功能发生障碍,从而引起的一组复杂临床综合征,主要表现为呼吸困难、疲乏和液体潴留(肺淤血、体循环淤血及外周水肿)等。根据左心室射血分数(LVEF),分为射血分数降低的心衰(HFrEF)、射血分数保留的心衰(HFpEF)和射血分数中间值的心衰(HFmrEF)。多数急性心衰患者经住院治疗后症状部分缓解,而转入慢性心衰;慢性心衰患者常因各种诱因急性加重而需住院治疗。

OCC云上东方会期间,南京医科大学第一附属医院黄峻教授阐述了慢性心衰药物治疗新进展,并指出目前临床上得到证实有效的药物为SGLT-2抑制剂达格列净和改善心肌细胞内代谢的维拉西胍,为心衰治疗带来新曙光。

慢性心衰应早诊断早治疗

2019年最新调查结果显示,在我国≥35居民中,加权后心衰患病率为1.3%,即大约1370万人患心衰,我国心衰患病率较15年前的调查结果增加了44%。

在这项最新调查中,研究者发现,我国≥35岁居民中,射血分数保留的心衰、射血分数中间值心衰、射血分数降低的心衰加权后患病率分别0.3%、0.3%、0.7%。

另外,1.4%的人存在左室收缩功能不全,即左心室射血分数<50%;35.5%存在左室舒张功能不全,2.7%存在中重度左室舒张功能不全。

原发性心肌损害和异常是引起心衰最主要的病因,除心血管疾病外,非心血管疾病也可导致心衰。识别这些病因是心衰诊断的重要部分,从而能尽早采取特异性或针对性的治疗。

慢性HFrEF的药物治疗

慢性HFrEF治疗目标是改善临床症状和生活质量,预防或逆转心脏重构,减少再住院,降低死亡率。

有效控制血压可降低因心衰住院、心血管事件及死亡率。按照目前高血压指南,将血压控制在130/80 mmHg以下。降压药物推荐优选ACEI/ARB、β受体阻滞剂。存在容量负荷过重的患者首选利尿剂。

对一些随机对照试验的回顾性分析以及荟萃分析表明,ACEI/ARB、β受体阻滞剂、醛固酮受体拮抗剂可能改善HFmrEF患者的预后。

图2  HFrEF患者药物治疗的5个步骤

慢性心衰药物治疗方案应达到优化

利尿剂:使患者处于“干重”状态

ACEI/或ARB/或沙库巴曲劼沙坦:达目标剂量或耐受剂量

β受体阻滞剂:达目标剂量或耐受剂量

螺内酯:最大剂量20 mg/天

伊伐布雷定:2.5-7.5 mg,bid,心率目标为60次/分左右

慢性心衰未来之星药物

2019年SGLT-2抑制剂开始推荐用于慢性心衰患者治疗,其全新作用机制为心衰治疗带来希望的曙光。

DAPA-HF是一项国际多中心、随机、双盲、安慰剂对照临床研究,评估在标准疗法基础上加用达格列净(10 mg/d)对比安慰剂的疗效和安全性差异,纳入的4744名受试者均为射血分数降低(LVEF ≤ 40%),伴或不伴2型糖尿病的心衰患者,平均年龄为66岁。

DAPA-HF研究证实,达格列净10 mg,1次/d,可显著降低HFrEF患者的心衰恶化风险、心血管死亡风险、全因死亡风险,无论是否合并糖尿病。推荐已使用指南推荐剂量ACEI/ARB、β受体阻滞剂及醛固酮受体拮抗剂或达到最大耐受剂量后,NYHA心功能Ⅱ~Ⅳ级、仍有症状的HFrEF患者,加用达格列净(10 mg、1次/d)(Ⅰ,B),以进一步降低心血管死亡和心衰恶化风险。

DAPA-HF研究结果显示,SGLT-2抑制剂显著降低伴或不伴糖尿病心衰人群心血管死亡或心衰恶化风险达26%,非糖尿病心衰人群显著降低心血管死亡或心衰恶化风险27%。

除此之外,VICTORIA III期研究发现维拉西胍可激活心衰患者可溶性鸟苷酸环化酶,研究结果提示,维拉西胍显著降低主要复合终点(CV死亡和心衰住院)。由此可见,类似维拉西胍的药物可以影响和改善心肌细胞内代谢途径的药物将成为重点对象和研究靶标。

图4  维拉西胍的作用机制示意图

综上所述,我国心衰患病率近十多年一直呈上升趋势,现已经达到1.3%,心衰患者达到1300例,慢性心衰常用七种药,方案为利尿剂基础上应用金三角即阻断RAAS药、B-B和螺内酯,窦性心率快者加用伊伐布雷定。近几年新出现并在临床上得到证实有效的药物为SGLT-2抑制剂达格列净和改善心肌细胞内代谢的维拉西胍,慢性难治性心衰可考虑短期间歇应用新型正形肌力药物左西孟旦。

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    2020-09-14 yangpeizhi
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1924144, encodeId=a6301924144f7, content=<a href='/topic/show?id=794d5803930' target=_blank style='color:#2F92EE;'>#新作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58039, encryptionId=794d5803930, topicName=新作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=24a22500182, createdName=1696533704_45270454, createdTime=Sun Jul 05 02:32:55 CST 2020, time=2020-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1725187, encodeId=3c9c1e2518717, content=<a href='/topic/show?id=58476021257' target=_blank style='color:#2F92EE;'>#曙光#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60212, encryptionId=58476021257, topicName=曙光)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=180c33737541, createdName=yangpeizhi, createdTime=Mon Sep 14 00:32:55 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1945851, encodeId=c0521945851ae, content=<a href='/topic/show?id=d6bd51951cd' target=_blank style='color:#2F92EE;'>#心衰药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=51951, encryptionId=d6bd51951cd, topicName=心衰药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c8f4467, createdName=AspirantSuo, createdTime=Sat Aug 08 03:32:55 CST 2020, time=2020-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=901565, encodeId=43f490156574, content=不错,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201123/916441d2913648269ede0b8db11ab6c2/0a36cd040f95424b9d105ae671387d9a.jpg, createdBy=52415437799, createdName=百度人生, createdTime=Mon Nov 23 20:44:33 CST 2020, time=2020-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=601707, encodeId=2d7b601e07f4, content=<a href='/topic/show?id=072c5088466' target=_blank style='color:#2F92EE;'>#心力衰竭#</a>SGLT2i与诺欣妥强強联合, beContent=null, objectType=article, channel=null, level=null, likeNumber=174, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50884, encryptionId=072c5088466, topicName=心力衰竭)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sun Jun 07 10:26:50 CST 2020, time=2020-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1353133, encodeId=4bbe135313376, content=<a href='/topic/show?id=1d931321816' target=_blank style='color:#2F92EE;'>#OCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13218, encryptionId=1d931321816, topicName=OCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sun Jun 07 05:32:55 CST 2020, time=2020-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1377518, encodeId=60ee13e7518d8, content=<a href='/topic/show?id=55f013219ae' target=_blank style='color:#2F92EE;'>#OCC 2020#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13219, encryptionId=55f013219ae, topicName=OCC 2020)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Sun Jun 07 05:32:55 CST 2020, time=2020-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039257, encodeId=5d5a103925e07, content=机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Fri Jun 05 17:32:55 CST 2020, time=2020-06-05, status=1, ipAttribution=)]
    2020-11-23 百度人生

    不错,学习了

    0

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    2020-06-07 lovetcm

    #心力衰竭#SGLT2i与诺欣妥强強联合

    0

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    2020-06-07 zhaojie88
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    2020-06-07 hmwwww
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    2020-06-05 肿肿

    机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要

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