ARB在心力衰竭中的应用.pptx

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年患者于患者于1 1年前于感冒后出现活动后气紧，经自服感冒药后好转。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，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后复发。为求进一步诊治，而于我院就诊。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。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，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地高辛BB BB（美托洛尔）（美托洛尔）ACEI ACEI（蒙诺）（蒙诺）ARB ARB（代文）（代文）氢氯噻嗪氢氯噻嗪安体舒通安体舒通长效硝酸盐制剂长效硝酸盐制剂肼苯哒嗪肼苯哒嗪曲美他嗪（万爽力）曲美他嗪（万爽力）辅酶辅酶Q10Q10速尿速尿硝酸甘油硝酸甘油硝普钠硝普钠多巴胺多巴胺多巴酚丁胺多巴酚丁胺氨力农氨力农米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从未使用过ARBARB和和ACEIACEI的心衰患者，是否必须经过的心衰患者，是否必须经过ACEIACEI，不，不能耐受才换为能耐受才换为ARBARB？已经在使用已经在使用ARBARB的心衰患者，是否应该换为的心衰患者，是否应该换为ACEIACEI？已经使用已经使用ACEIACEI的心衰患者，是否可以加用的心衰患者，是否可以加用ARBARB？是否所有的心力衰竭都适合使用是否所有的心力衰竭都适合使用ARBARB？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 ARBVALIANT 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 OPTIMAAL:Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartanwith the Angiotensin Antagonist Losartan DesignDesignMulticenter,multinational,randomized,double-blind,parallel-groupMulticenter,multinational,randomized,double-blind,parallel-groupPatientsPatients5466 patients aged 5466 patients aged 50 years with acute MI and evidence of heart failure 50 years with acute MI and evidence of heart failure or left ventricular dysfunction(left ventricular ejection fraction 35%)or left ventricular dysfunction(left ventricular ejection fraction 35%)Follow up and primary endpointFollow up and primary endpointPrimary endpoint:all-cause mortality.Mean 2.7 years follow upPrimary endpoint:all-cause mortality.Mean 2.7 years follow upTreatmentTreatmentCaptopril(titrated to target dose 50 mg three times daily,as tolerated)or Captopril(titrated to target dose 50 mg three times daily,as tolerated)or losartan(titrated to target 50 mg daily,as tolerated)losartan(titrated to target 50 mg daily,as tolerated)OPTIMAAL:Optimal Trial In Myocardial Infarction OPTIMAAL:Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartanwith the Angiotensin Antagonist Losartan-RESULTS continued-RESULTS continued-Months after randomizationMortality(%)0061218243036510152025All-cause mortalityDickstein et al.Lancet 2002;360:75260.P=0.069RR 1.13(95%CI 0.991.28)CaptoprilLosartanOPTIMAAL:Optimal Trial In Myocardial Infarction OPTIMAAL:Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartanwith the Angiotensin Antagonist Losartan-RESULTS continued-RESULTS continued-Months after randomizationEndpointrate(%)0061218243036Secondary and tertiary endpointsDickstein et al.Lancet 2002;360:75260.RR 1.19(95%CI 0.981.43)P=0.072CaptoprilLosartan05101551015Sudden cardiac death or cardiac arrestRR 1.03(95%CI 0.891.18)P=0.72ReinfarctionOPTIMAAL:Optimal Trial In Myocardial Infarction OPTIMAAL:Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartanwith the Angiotensin Antagonist Losartan-RESULTS continued-RESULTS continued-Months after randomizationHospitalization(%)006121824303620406080All-cause hospitalizationRR 1.03(95%CI 0.971.10)P=0.36CaptoprilLosartanDickstein et al.Lancet 2002;360:75260.OPTIMAAL:Optimal Trial In Myocardial Infarction OPTIMAAL:Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartanwith the Angiotensin Antagonist Losartan-SUMMARY-SUMMARY-In patients with acute MI and evidence of heart failure or left In patients with acute MI and evidence of heart failure or left ventricular dysfunction,losartan 50 mg daily:ventricular dysfunction,losartan 50 mg daily:Conferred no benefit in comparison with captoprilConferred no benefit in comparison with captopril Was better tolerated than captoprilWas better tolerated than captoprilACE inhibitors therefore remain the first-choice therapy in this groupACE inhibitors therefore remain the first-choice therapy in this groupRESOLVED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ACEIAHA/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 designMcMurray JJV et al.Lancet.2003;362:761-71.Candesartan in Heart failure:Assessment of Reduction in Mortality and morbidity(CHARM)-AddedRandomized,double-blindNYHA class IIIV,LVEF 40%,stable ACEI dose for 30 daysN=2548Candesartan 32 mg qdn=1276Placebo n=1272Median follow-up:41 monthsPrimary outcome:CV death or hospitalization for HF ACEI=angiotensin-converting enzyme inhibitorCHARM-Added:Primary outcome of CV death CHARM-Added:Primary outcome of CV death or HF hospitalizationor HF hospitalizationN=2548McMurray 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)NoYesNoYes125712912019529254820284576 0.26 0.29Patients(n)Candesartan betterPlacebo betterP value for interaction0.60.811.2Hazard 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：概述研究英文名称研究英文名称The The ONONgoing going T Telmisartan elmisartan A Alone andlone andin combination with in combination with R Ramipril amipril GGlobal lobal E Endpoint ndpoint T Trialrial研究中文名称研究中文名称替米沙坦单药或者联合雷米普利终点研究替米沙坦单药或者联合雷米普利终点研究研究设计研究设计随机、双盲、对照、非劣效性研究随机、双盲、对照、非劣效性研究随访随访5.55.5年年研究人群研究人群5555岁、存在冠心病、外周血管疾病、脑血管疾病或糖尿病伴靶岁、存在冠心病、外周血管疾病、脑血管疾病或糖尿病伴靶器官损伤的患者器官损伤的患者 (N=25,620)(N=25,620)研究分组、治研究分组、治疗方案疗方案替米沙坦单药组、雷米普利单药组、替米沙坦雷米普利组替米沙坦单药组、雷米普利单药组、替米沙坦雷米普利组主要终点主要终点复合终点：心血管死亡、心肌梗死、卒中或心衰住院复合终点：心血管死亡、心肌梗死、卒中或心衰住院次要终点次要终点主要的次要终点：心血管死亡、心肌梗死、卒中的复合终点主要的次要终点：心血管死亡、心肌梗死、卒中的复合终点其他次要终点：新发心衰、糖尿病其他次要终点：新发心衰、糖尿病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、肾功联合治疗不良事件发生率更高：低血压、肾功能不全能不全End point End point RRRR95%CI95%CIp for p for heterogeneityheterogeneityMortality Mortality 0.970.970.921.030.921.030.490.49Fatal MI Fatal MI 0.970.970.761.220.761.221.01.0Nonfatal MINonfatal MI0.910.910.781.070.781.070.310.31Hospitalizations-CHFHospitalizations-CHF0.810.810.720.910.720.910.040.04Hospitalizations overallHospitalizations overall0.920.920.821.050.821.050.030.03HyperkalemiaHyperkalemia1.951.950.854.480.854.480.010.01Renal dysfunction Renal dysfunction 1.911.911.402.601.402.600.110.11Hypotension Hypotension 1.571.571.431.711.431.711.01.0Medication discontinuedMedication discontinued1.211.211.071.371.071.370.140.14Meta-analysis:Combined therapy with ACE inhibitors and ARBs vs ACE-inhibitor therapy alone in patients with heart failureKuenzli A.European Society of Cardiology 2009 Congress;August 30-September 2,2009;Barcelona,Spain.没有绝对的真理细分病人群才是硬道理EF值很低，静脉使用多巴酚丁胺LVEF 25%26%是否所有的心衰都应该使用ARB？瓣膜病心衰舒张性心衰舒张性心衰总结ARB在心衰治疗中有重要作用，部分药物与ACEI的益处可能相当ARB与ACEI联用，副作用几率增加，但在严重低EF值患者，可能好处大于坏处ARB只能用于心肌收缩功能降低的心力衰竭谢 谢!