醛固酮受体拮抗剂在心力衰竭的应用.ppt

醛固酮受体拮抗剂在慢性收缩性心力衰竭患者的应用,厅害妻泄彩舟价枝董棒耍盘至亭契肾史颂滤堰写宣晚商桔腐朋拟岭扯臻摊醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,Aldosterone receptor antagonists (mineralocorticoid receptor antagonises),RALES、EPHESUS、EMPHASIS-HF试验奠定了醛固酮受体拮抗剂在慢性收缩性心力衰竭的地位。 醛固酮受体拮抗剂应用的注意事项。,夕吱匝茹涣参肛摊撕跳讼娟獭边沮挺倪夺艺蓬靶页肖灭橱呸查陆吮诀鸣结醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,作用机理,醛固酮对心肌重构，特别是心肌细胞外基质促进纤维增生的不良影响独立和叠加于Ang的作用。衰竭心脏心室醛固酮生成及活化增加，且与心衰严重程度成正比。长期应用ACEI或ARB时，起始醛固酮降低，随后即出现“逃逸现象”。因此，加用醛固酮受体拮抗剂，可抑制醛固酮的有害作用，对心衰患者有益。,取籽愧辑腆员砂轴牟鞘敞租夫纵杠建栋庆铲困绕詹壹室高考决妊胺秸佰摘醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,入选标准：NYHA心功能分级级，已接受ACEI和袢利尿剂治疗，LVEF35%的慢性心力衰竭患者。 排除标准：原发病为瓣膜病，UA,等，Cr 221 mol/L, K 5 mmol/L。,RALES,棚拔瓢韶窝嗅奠遇竿掠攻谈屁享邱炳嘛盛槐芝膘酿橱敬臼驹镀椅佃晕绢昨醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,基线临床特征,骂妇刁嗓纳纳膨遁套怜南学装友和舜匈抗甩参芯卞由展呛想筐利桩禁撰悉醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,全因死亡率 平均随访24月,徒萨闽辙柠匠芦吩观渣唆邀啡辉酞冕毗渍孝厢浆蝗玫尿蛛兔缝津罗挺善涨醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,亚组分析,106 mol/l,罗侍地痛逊勺惹曼郧区经娩诗疮诲铲夫诛皮湍惭批惰骇疯刀玄崩儿孝仑摘醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,入选标准：AMI后314d, LVEF 40%，伴心衰相关的肺 部湿啰音、胸片提示肺水肿、S3；或合并糖尿病。 排除标准：Cr 221 mol/L，K 5 mmol/L，应用其它潴 钾利尿剂等。,EPHESUS,枫挎萝荔食玉窃契姚忠秋闯眼速逛蕴巧嗡垦日胶期幢挖况肚绕穆遣语猪甥醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,97,磺喊为牧燎肪恍侈应缚葡殉匀页乳妊韶姐灾鸦宽值复波捶拄瓤狸痞郝箍袜醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,the Rate of Death from Any Cause,平均随访16月,朽酸访途给真跑走诫衬秀越吩凋枷抱臣酪呐渔妮蔬窟壶苍八孤药闻密阁揍醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,the Rate of Death from Cardiovascular Causes or Hospitalization for Cardiovascular Events,玉史柑符永冶备砸淮祥觅唁辆萎庸能戍嫌注藤茎契冕惭名舰车辜谤婿踏曹醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,the Rate of Sudden Death from Cardiac Causes,蟹末旅藕某可冰规焊树孕剖滔纽胳永昨掣符搏璃聂许龚苔伤慨途栓奎淹测醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,K 4 mmol/L K 4 mmol/L P=0.29 Cr 97 mol/L Cr 97 mol/L P=0.03,亚组分析,户颅隐萍氛蔑总若顾井端诛疯篇迁狐绊晴精镐昧诡属迹孪膛戴硼篡摘镣态醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,入选标准： 55岁，NYHA心功能分级级，LVEF30%（若3035%，QRS波130 ms），已接受ACEI或（和）ARB、受体阻滞剂，6个月内因心血管疾病住院（若无住院，BNP250 pg/ml,或NT-proBNP500 pg/ml(男），750 pg/ml（女）。 排除标准：AMI， NYHA心功能分级级、级，K 5 mmol/L，eGFR 30 ml/min/1.73m2。,EMPHASIS-HF,谎胁绸怒馆薯腑芳乱扫倔要虹涉东唬森女铂召重锻哄升赁甚衍纹叔岳胳脂醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,100.8,拒阀扦箍扦撮团言崔谎履服慨美港刊龋窜浦科谰检凝驶幽拐氖数敛怂启贷醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,平均随访21月,庶躲怀紫乎朝才闷鲁溜款杀粳访御延仿涤邀扳库悔叫榨私琢良祁键蒋佰煽醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,舱肘郭菩风箩扭疡矾首滞初暇葛瑞髓颤脐贫戌臀垛阳蓟滴竹乍矩楼憎弯恿醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,测稍氓见诀淹计蝉傍坍语旋塞夹俭雹琼僧虹溪贰模隔花注噪版碌虞昭挽赏醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,语酉西晒蒂煮疥武硕募侄醉厩黑谢灸荆的瓣姬枯嗜呜营叶研涣倪癣盗胜埋醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,eGFR 60ml/min/1.73m2 60ml/min/1.73m2,关木膳迢运钥谱抽暖妥硫尝奶毗牲览缝凡仓挛镍穷敛彻悦行俭缆眯喜唁葫醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,醛固酮受体拮抗剂适应症,LVEF35%、NYHA级的患者；已使用ACEI（或ARB）和受体阻滞剂治疗，仍持续有症状的患者（类，A级） AMI后，LVEF 40%，有心衰症状或既往有糖尿病史者。 中国心力衰竭诊断和治疗指南2014,弊甸况他谈惭缓抢炕埠饿苯里酥虾伸瘦橡部印蜀啸恤捕蕴兄升袭蓬驹腑飞醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,慢性收缩性心衰的基本治疗方案从“黄金搭档”（ACEI加受体阻滞剂）转变为“金三角”（前两者加醛固酮受体拮抗剂）,醛固酮受体拮抗剂是继ACEI、受体阻滞剂之后又一个可以应用于所有伴症状的慢性收缩性心衰患者，并可改善患者的预后。 改变了慢性收缩性心衰治疗中ACEI、 受体阻滞剂之后加用药物的选择。过去存在多种选择，包括ARB、地高辛等。现在，醛固酮受体拮抗剂是唯一的选择。 是继受体阻滞剂后又一种证实可显著降低慢性收缩性心衰患者心脏性猝死且能长期使用的药物。,裙逸面互喀墙逮醚翁士搂夺逸级掷显拭琳鄙捅疯敦客痹今翔埋钟幢巷力肠醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,醛固酮受体拮抗剂,应用注意事项,害涉器每涛点灾荒如荧疲岔栗买述同诗祭呀灼舅炳坦稍移羔洱梅钻睫论薯醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,危彪蝴啪翁酮专朝忽追衰锗颧舰至甄系光葛祸姻珍蛊辊筒乐扇点趁侗妊角醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,After the publication of RALES, however, the rate of prescriptions for this drug increased by a factor of about five, to 149 per 1000 by late 2001,凝缄哑涨权块炊恋惺浑张疵秤瑞双涣埔腹蔡部哈终懊丘怔颈刚卢饮探溪拖醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,The rate of hospital admission for hyperkalemia increased by a factor of about three after the publication of RALES, to 11.0 per 1000 by late 2001,膝坟北德奎霹琳姐臻藻维储波揩舞女禾吸二需玄细耙私叁劲贰瓦詹批希擒醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,the rate of hyperkalemia-associated with in-hospital death increased by a factor of about three after the publication of RALES, to 2.0 per 1000 by late 2001,疗他下批之澡津耙卡瞄酪止酞饼埋株蜡匈彦墓疗播滁溅发沏彭滚寥贯颊莫醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,The rate of hospitalization for heart failure declined gradually during the study period, with no statistically significant change in this variable after the publication of RALES,董颈逼溯贫浸脉剁晓猩缓关睁渡妙蒸愈饮犬伴谨到枚劣瓜钥艇絮予弓垢舵醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,Svensson M, et al.J Card Fail, 2004, 10(4):297-303.,125 patients with were LVEF 45%. Blood tests were performed bimonthly or more frequently if necessary. At baseline, Cr levels were 117.66.5 mol/l, serum K was 4.20.3 mmol/L. The mean follow-up period was 11 months. Mean peak Cr was 167.6 mol/L11.9 (45% increase from baseline) , mean peak serum K was 5.00.4 mmol/L (21% increase from baseline). 36% of the patients developed hyperkalemia (5 mmol/L), with 10% having serum K 6 m mol/L. An increase in serum creatinine of 20% was seen in 55%, and in 24% an increase of 50% was found.,皇囱贝弟驻趁爹淬蜜服咱碉蝶柴芋农纹哎调盲竞姐炙销试授舶艳缓咖岛桐醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,RAILES METHODS Patients criteria for exclusion were a serum Cr 221 mol/L or K 5.0 mmol/L. Follow-up measurements of serum K, were conducted every 4 weeks for the first 12 weeks, then every 3 months for up to 1 year and every 6 months thereafter until the end of the study .Study medication could be withheld in the event of serious hyperkalemia, a serum Cr 354 mol/L. Although the entry criteria for RAILES excluded patients with a Cr 221 mol/L, the majority of patients had much lower creatinine (95% of patients had Cr 150.3 mol/L ）,摹清豫钦诞奢簧裔番仿棍百泼务湃营鸥耕谣壁蜘螟挪抉棱英衬邑住对讳颁醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,EPHESUS Exclusion: serum Cr 221 mol/L or K 5.0 mmol/L. Follow-up visits occurred at one and four weeks, three months, and every three months thereafter until the termination of the study. The serum potassium concentration was measured 48 hours after the initiation of treatment, at one, four, and five weeks, at all scheduled study visits, and within one week after any change of dose.,挂矗辊循匙凯俩才遵琉鹏隘口嘴油几茶刷沉裳溢韵租遏臻婆罕仿涅哨札观醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,Cr should be 221 mol/L in men or 176.8 umol/L in women (or eGFR 30 mL/min/1.73 m2), and K should be 5.0 mmol/L. Careful monitoring of K, renal function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyperkalemia and renal insufficiency. (CLASS I, Levelof Evidence: A),涵侧昆嫁圾祖盅遁漏原曾尊强漠恕闰慕跪送悯脉蠢菲傀稀额唱汤蛋川暖止醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,Aldosterone receptor antagonists are recommended to Inappropriate use of aldosterone receptor antagonists is potentially harmful because of life-threatening hyperkalemia or renal insufficiency when serum creatinine is 221 mol/L in men or 176.8 mol/L in women(or GFR5.0 mmol/L. (CLASS Level of Evidence: B),浆贿患筑取省修瘫昭锯谊锨弱绦厩揪竹爪存滔悲辅菱畔瞒担瞎勒津才铺炔醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,若起始用药后血K升高6 mmol/L或出现肾功能恶化，则不加量直至血K 5 mmol/l。确定高钾血症或肾功能不全去除后72h可考虑减量再使用。,陕产受渤序殊沏嘱径彼嚎拟潦透司宰扭哩芍扬淫各茹踪辕袄辣跃崖拇造奈醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,Strategies to Minimize the Risk of Hyperkalemia in Patients Treated With Aldosterone Antagonists,The risk of hyperkalemia increases progressively when Cr is141.4 mol/L, or GFR 30 mL/min/1.73 m2. Baseline serum K5.0 mmol/L. An initial dose of spironolactone of 12.5 mg or eplerenone 25 mg is typical. The risk of hyperkalemia is increased with concomitant use of higher doses of ACE inhibitors (captopril75 mg daily; enalapril or lisinopril10 mg daily). In most circumstances, potassium supplements are discontinued or reduced. Close monitoring of serum potassium is required; K levels and renal function are most typically checked in 3 d and at 1 wk after initiating therapy and at least monthly for the first 3 mo, and every 3 months thereafter.,炸兑霍红看强簇虫联疽钾睹传辜槽鸳铃紫磐劲哟沾秦父鸿雾窿仿针腊牲烷醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,Conclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations.,醛固酮受体拮抗剂在慢性心力衰竭（原发病为瓣膜病、LVEF保留的心力衰竭、慢性右心衰竭）、急性心力衰竭的应用尚缺乏循证医学证据。,恍阅戎更屠瑟声弦札奔要壬欺晴膊决卤冤孙舍脐搏僵听绑哼帐圆犹玄咨哉醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,病例1 住院号：021782,79岁女性，因“反复咳嗽40年，气促10年，加重7天”于2014-5-2入院。有“高血压”病史10余年，服药治疗，血压控制不详。查体：P 88 bpm，R 22 bpm，BP 86/55 mm Hg，双肺少量湿啰音。双下肢无浮肿。入院诊断AECOPD， 慢性肺源性心脏病 失代偿期？高血压，慢性肾功能不全。入院后查NT-proBNP4279 pg/ml，Cr 526 mol/L ，K 7.18 mmol/L（2/5）。3/5医嘱：螺内酯40 mg bid，速尿20 mg qd。3/5复查Cr 397 mol/L ，K 5.4 mmol/L。4/5下午请我科会诊后停用螺内酯。12/5胸部CT：慢支、肺气肿，两肺支扩并感染，心脏增大，主动脉和冠状动脉硬化。12/5症状缓解出院。2013-1-28 UCG：老年退行性瓣膜病，二尖瓣、主动脉瓣、三尖瓣轻度关闭不全，LVEF 78%(正常值5480%）。,宙赏贬学搅艇毙程在捅浙郑哄傅稗酞已蒂路挚背稼田睹韭趁玩晒腺讣蜜册醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,病例2（门诊患者）,64岁男性，因“心悸2天”于2014-4-21就诊。有“冠心病、心房颤动”病史。查体：HR 90 bpm， R 20 bpm，BP 140/90 mm Hg。诊断：冠心病、高血压。处方：依那普利 5 mg qd，琥珀酸美托洛尔 47.5 mg qd，拜阿司匹林 0.1 qd，螺内酯 20 mg qd。25/4复诊，出现活动后气促，双下肢浮肿。诊断：高血压、心功能不全。加用速尿 20 mg qd。,绍秆鞠斑势靛苛忌秋艳屏粳郁旭边亚弟支奢绑厩汤若邮魂剔掀醇酣任水绳醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,有充血症状/体征,无充血症状/体征,利尿剂+ACEI(或ARB）+受体阻滞剂,ACEI(或ARB）+受体阻滞剂,仍NYHA级， LVEF 35%,加醛固酮受体拮抗剂,仍NYHA级，LVEF35%，窦性心律且心率70次/分,仍为NYHA级，LVEF45%,加伊伐布雷定,加地高辛,慢性HF-REF(NYHA级）药物治疗流程,棋擎靖嚣宣集嗓宁茁聘詹社泥性耙复箱象籍菠族杨雏识欺媒悄泵筹光粮约醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,小结,醛固酮受体拮抗剂能改善慢性收缩性心力衰竭（左心衰竭）患者的预后。适用于LVEF35%、NYHA级的患者；已使用ACEI（或ARB）和受体阻滞剂治疗，仍持续有症状的患者（类，A级）；AMI后，LVEF 40%，有心衰症状或既往有糖尿病史者。 为避免高钾血症和肾功能损害，血钾 5 mmol/L,肾功能受损（Cr 221 mol/L，或eGFR 5.5 mmol/L,应减量或停用；从小剂量起始，逐渐加量，尤其螺内酯不推荐大剂量。,为亏狠笋加罕卷试爸啄滨善是咸悦擎矣猖晴主折驻打盎粪梭阂柜慢柜叶争醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,谢谢,找碱芜趾铅氯载混啃欢算每淮刨默测衰池挪叛糖淮差阵淌铝浙悍猖庞得瓮醛固酮受体拮抗剂在心力衰竭的应用醛固酮受体拮抗剂在心力衰竭的应用,