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循证证据夯实地位:高选择性β1受体阻滞剂心血管获益更佳

2018-07-13 MedSci 国际循环

在最新欧洲高血压指南中,β受体阻滞剂作为一线治疗药物予以推荐(Ⅰ,A)。指南推荐源自循证证据,在高血压治疗领域,β受体阻滞剂的应用仍处于不断研究探索之中。

在最新欧洲高血压指南中,β受体阻滞剂作为一线治疗药物予以推荐(Ⅰ,A)。指南推荐源自循证证据,在高血压治疗领域,β受体阻滞剂的应用仍处于不断研究探索之中。近期,Pharmacol Res杂志发表的一项基于英国临床事件研究数据库(CPRD)的真实世界研究显示,与其他β受体阻滞剂或非β受体阻滞剂单药治疗相比,高选择性β1受体阻滞剂比索洛尔为高血压患者带来的长期生存获益更佳。这一结果的公布引发了临床医生对β受体阻滞剂临床应用现状的思考。本期解读为大家带来大连医科大学附属第一医院姜一农教授、西安交通大学医学院附属第一医院牟建军教授和新疆医科大学第一附属医院徐新娟教授的精彩观点。

真实世界研究证实比索洛尔可带来长期生存获益

姜一农教授:该研究从来自数百个诊所的500多万人中筛选了10万余例受试者,从中可以肯定β受体阻滞剂的降压作用毋庸置疑。研究对β1受体选择性高的比索洛尔与其他β受体阻滞剂进行了比较,确定了相对较新、药代动力学较好、受体选择性较高、长效的脂溶性β受体阻滞剂作为降压药物降低事件的作用不劣于其他药物。实际上,β1选择性高的β受体阻滞剂如比索洛尔一直被作为降压药物使用,且β受体阻滞剂与钙通道阻滞剂联用的降压效果较好,临床上不可缺少。另外,β受体阻滞剂在合并心衰、冠心病的患者中应用疗效确切,对于心率较快的高血压患者更是首选。因此,临床应用时可选择β1选择性较高、药代动力学较好的β受体阻滞剂。该研究不足之处是比索洛尔组患者例数较少。

徐新娟教授:基于CPRD的大规模比索洛尔真实世界研究显示,与其他非β受体阻滞剂降压药物相比,比索洛尔的长期生存获益更佳。此前,不论是英国指南,还是美国指南,均未将β受体阻滞剂列为一线治疗药物。这项研究可能会改变一些人对β受体阻滞剂的看法。结合CPRD中8万多人的大数据分析结果,可以说β受体阻滞剂应该能够被高血压专家和心血管专家再次接受,在高血压治疗领域起其应有的作用。

高选择性β1受体阻滞剂比索洛尔优势显著

姜一农教授:药代动力学、β1选择性、有无拟交感活性等是决定β受体阻滞剂疗效的关键。无拟交感活性可确保β受体阻滞剂的治疗效果,并减少不良反应;脂溶性β受体阻滞剂的药代动力学特点是分布较广,不良反应较小,肝肾负担更小,起效缓慢但作用长效。这类药物如比索洛尔半衰期较长,对于夜间及清晨血压和心率的控制均有益,应该是更好的β受体阻滞剂选择。既往我们开展的CREATIVE研究比较了富马酸比索洛尔和美托洛尔缓释片对轻中度高血压患者治疗12周后服药最后4小时的平均动态心率和血压的控制情况。结果发现,比索洛尔具有一定优势,可改善清晨交感神经异常兴奋,这可能部分解释其对减少事件进一步获益的机制。鉴于以上作用优势,比索洛尔的疗效更好。

徐新娟教授:众所周知,药物的选择性越高,治疗不良反应相对越少。例如,对于哮喘患者,高选择性β受体阻滞剂的应用限制就较少。此外,比索洛尔主要阻断β1受体,故其对血糖、体重及男性性功能的影响相对较少。而且,β受体阻滞剂针对的是交感神经过度兴奋和肾素-血管紧张素-醛固酮系统激活的患者。交感神经过度兴奋会导致心血管不良事件风险增加,包括猝死、心律失常。此前多项有关使用阿替洛尔的RCT研究提示其不良反应较大,原因在于该药有拟交感作用。相比之下,比索洛尔无拟交感作用。荟萃分析也提示,随着比索洛尔治疗时间延长,患者死亡率和心血管事件发生率均下降。

牟建军教授:在找准适应证的前提下,尽量选择β1受体选择性高的β受体阻滞剂如比索洛尔,既能有效降低血压和心血管风险,又能避免一些不良反应。此外,还需选择好应用剂量,在治疗过程中监测血压和心率,从而使二者均达标。

分析药物特点和患者病情,改善β受体阻滞剂的临床应用

姜一农教授:β受体阻滞剂异质性大,临床选择时要区别对待,建议选择β1选择性高、半衰期长、水脂双溶性好、无内在拟交感活性的β受体阻滞剂。当然,临床选择β受体阻滞剂时还需充分考虑不同药物的独特优势。目前临床上冠心病、尤其是心衰患者中β受体阻滞剂的应用明显不足。此外,对于其他患者如心率>80次/分的年轻高血压患者、更年期女性高血压患者,临床医生可能未能处方β受体阻滞剂,可能影响这些患者的血压达标。临床实践中,建议同时监测患者的血压和心率,对于心率明显偏快如>80次/分者,应该使用β受体阻滞剂。

牟建军教授:第一,研究发现,即使在心血管一级预防中,年轻高血压患者仍可从β受体阻滞剂治疗中明显获益,尤其具有高度选择性的β1受体阻滞剂。β受体阻滞剂尤其是具有高度选择性的β受体阻滞剂在高血压治疗中的循证证据是明确的。第二,近年来,中国高血压患者数量不断增长,β受体阻滞剂的适用人群也在相对增加。临床实践中,我们发现很多年轻高血压患者的心率较快,交感神经兴奋导致的高血压人群增加,实际上也增加了临床应用β受体阻滞剂治疗高血压的必要性。第三,中国高血压患者即使血压达标但仍有很多患者心率偏快,达到中国专家共识推荐的80次/分者仍较少。这也是导致高血压患者降压达标但仍存在心血管风险的重要原因之一。

原始出处:
MeritxellSabidó, et al. Pharmacological intervention in hypertension using beta-blockers: Real‐world evidence for long-term effectiveness. Pharmacological Research. Volume 130, April 2018, Pages 191-197.

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  5. [GetPortalCommentsPageByObjectIdResponse(id=1922910, encodeId=ea55192291059, content=<a href='/topic/show?id=78f794e800a' target=_blank style='color:#2F92EE;'>#选择性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94780, encryptionId=78f794e800a, topicName=选择性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0802500050, createdName=肉我只吃一口, createdTime=Thu Nov 01 17:16:00 CST 2018, time=2018-11-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2085798, encodeId=057a2085e9839, content=<a href='/topic/show?id=723a9e69383' target=_blank style='color:#2F92EE;'>#阻滞剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97693, encryptionId=723a9e69383, topicName=阻滞剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=40be178, createdName=zhyy88, createdTime=Thu May 16 01:16:00 CST 2019, time=2019-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822361, encodeId=40f61822361c7, content=<a href='/topic/show?id=36a3102e5706' target=_blank style='color:#2F92EE;'>#高选择性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102757, encryptionId=36a3102e5706, topicName=高选择性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8dba135, createdName=xuyong523, createdTime=Sat May 18 11:16:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995183, encodeId=c4c519951835a, content=<a href='/topic/show?id=347538040cf' target=_blank style='color:#2F92EE;'>#受体阻滞剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38040, encryptionId=347538040cf, topicName=受体阻滞剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=54f9127, createdName=tulenzi, createdTime=Tue Mar 05 21:16:00 CST 2019, time=2019-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1449760, encodeId=0ee91449e60f4, content=<a href='/topic/show?id=0bd850468be' target=_blank style='color:#2F92EE;'>#循证#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50468, encryptionId=0bd850468be, topicName=循证)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fca95510093, createdName=xjy04, createdTime=Sun Jul 15 08:16:00 CST 2018, time=2018-07-15, status=1, ipAttribution=)]
    2018-07-15 xjy04
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