ARB 在心力衰竭中的应用

ARB在心力衰竭治疗中的应用,男性，57岁，农民 反复活动后心累、气促1年,患者于1年前于感冒后出现活动后气紧，经自服感冒药后好转。后多次于受凉后发生活动后气紧，并逐渐出现双下肢水肿，经当地医院（具体不祥）治疗后好转。后多次于劳累或感冒后复发。为求进一步诊治，而于我院就诊。患病以来，精神较差，饮食不佳，小便有所减少。既往有长期大量饮酒史,T：36.3 P：85次/分，R：22次/分 BP：120/78 mmHg 氧饱和度：92%端坐位，呼吸急促。颈静脉充盈，肝颈征阳性。双肺中下份湿鸣明显，较对称，未闻及干鸣音。心界叩诊不清，似有明显长大，心率120次/分，余心脏听诊不理想。腹软，肝界长大，肋下2cm肝下5cm。双下肢水肿,常规及生化检查基本正常冠脉造影基本正常,治疗所选择的药物,地高辛BB （美托洛尔）ACEI （蒙诺）ARB （代文）氢氯噻嗪安体舒通长效硝酸盐制剂肼苯哒嗪曲美他嗪（万爽力）辅酶Q10,速尿硝酸甘油硝普钠多巴胺多巴酚丁胺氨力农米力农,治疗最基本的药物,氢氯噻嗪ACEI or ARBBB 美托洛尔安体舒通地高辛,I 类,答案似乎很简单，在不能耐受ACEI后可以选择ARB,但临床永远不会那么简单,从未使用过ARB和ACEI的心衰患者，是否必须经过ACEI，不能耐受才换为ARB？已经在使用ARB的心衰患者，是否应该换为ACEI？已经使用ACEI的心衰患者，是否可以加用ARB？是否所有的心力衰竭都适合使用ARB？,从未使用过ARB和ACEI的心衰患者，是否必须经过ACEI，不能耐受才换为ARB？,ACEI vs ARB,VALIANT 研究设计,N=14703,急性心肌梗死（0.5-10天），合并心力衰竭的临床/放射影像学证据和/或左室收缩功能障碍,主要终点：全因死亡率次要终点：心血管死亡、心力衰竭住院、心肌梗塞复发,平均随访时间：24.7月事件驱动,卡托普利50mg tid（n=4909）,缬沙坦 160mg Bid（n=4909）,卡托普利50mg tid+ 缬沙坦 80mg Bid（n=4885）,随机、双盲、活性药对照,死亡率和联合终点比较,至少缬沙坦不比卡托普利差,OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan,DesignMulticenter, multinational, randomized, double-blind, parallel-groupPatients5466 patients aged 50 years with acute MI and evidence of heart failure or left ventricular dysfunction (left ventricular ejection fraction 35%)Follow up and primary endpointPrimary endpoint: all-cause mortality. Mean 2.7 years follow upTreatmentCaptopril (titrated to target dose 50 mg three times daily, as tolerated) or losartan (titrated to target 50 mg daily, as tolerated),OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan- RESULTS continued -,Months after randomization,Mortality,(%),0,0,6,12,18,24,30,36,5,10,15,20,25,All-cause mortality,Dickstein et al. Lancet 2002; 360:75260.,OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan- RESULTS continued -,Months after randomization,Endpoint,rate (%),0,0,6,12,18,24,30,36,Secondary and tertiary endpoints,Dickstein et al. Lancet 2002; 360:75260.,RR 1.19(95% CI 0.981.43),P = 0.072,Captopril,Losartan,0,5,10,15,5,10,15,Sudden cardiac death or cardiac arrest,RR 1.03(95% CI 0.891.18),P = 0.72,Reinfarction,OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan- RESULTS continued -,Months after randomization,Hospitalization,(%),0,0,6,12,18,24,30,36,20,40,60,80,All-cause hospitalization,Dickstein et al. Lancet 2002; 360:75260.,OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan- SUMMARY -,In patients with acute MI and evidence of heart failure or left ventricular dysfunction, losartan 50 mg daily:Conferred no benefit in comparison with captoprilWas better tolerated than captoprilACE inhibitors therefore remain the first-choice therapy in this group,RESOLVED结论：坎地沙坦和卡托普利一样有效和安全，联用对防止左室重构比单用任何药物都有效,ARB在心衰中的作用，部分药物不劣于ACEI,AHA/ACC 2009 guideline,IIa Angiotensin II receptor blockers are reasonable to use as alternatives to ACE inhibitors as first-line therapy for patients with mild to moderate HF and reduced LVEF,已经在使用ARB的心衰患者，是否应该换为ACEI？,已经使用ACEI的心衰患者，是否可以加用ARB？,缬沙坦 vs 安慰剂,绝大多数都在服用ACEI,生存率没有差别,事件发生率缬沙坦组明显为低,缬沙坦与ACEI联用降低事件发生率但不应该与ACEI及BB联用,Relationship of background ACEI dose to benefits of candesartan in the CHARM-Added trial,CHARM-Added: Study design,McMurray JJV et al. Lancet. 2003;362:761-71.,Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added,Randomized, double-blindNYHA class IIIV, LVEF 40%, stable ACEI dose for 30 daysN = 2548,Candesartan 32 mg qdn = 1276,Placebo n = 1272,Median follow-up: 41 months,Primary outcome: CV death or hospitalization for HF,ACEI = angiotensin-converting enzyme inhibitor,CHARM-Added: Primary outcome of CV death or HF hospitalization,N = 2548,McMurray JJV et al. Am Heart J. 2006;151:985-91.,Recommended dose of ACEICHARM prespecifiedMaximum dose of ACEIFDA 2005CHARM-AddedCHARM-AlternativePooled results (low LVEF patients),NoYesNoYes,125712912019529254820284576,0.26 0.29,Patients (n),Candesartan better,Placebo better,P value for interaction,0.6,0.8,1,1.2,Hazard ratio (95% Cl),CHARM-Added 结论,坎地沙坦降低心血管死亡及事件发生率，无论是否使用ACEI，而且在高剂量ACEI病人中都有好处联用坎地沙坦相较单独使用ACEI，有更大的益处。,McMurray JJV et al. Am Heart J. 2006;151:985-91.,是否每一个心衰患者，都要ARB+ACEI联用？,2008 ESC 指南确定为I类适应证,ONTARGET：概述,ONTARGET：雷米普利 vs. 雷米普利替米沙坦主要终点无显著差异,替米沙坦雷米普利替米沙坦+雷米普利,随访时间（年）,累积事件发生率（%）,ONTARGET 总结,Telmisartan vs. Ramipril主要终点：非劣于雷米普利低血压发生率显著高于雷米普利Telmisartan plus Ramipril vs. Ramipril联合治疗未较单药带来更多收益联合治疗不良事件发生率更高：低血压、肾功能不全,Meta-analysis: Combined therapy with ACE inhibitors and ARBs vs ACE-inhibitor therapy alone in patients with heart failure,Kuenzli A. European Society of Cardiology