arb在心力衰竭中的應(yīng)用

1、ARB在心力衰竭治療中的應(yīng)用,,男性，57歲，農(nóng)民 反復活動后心累、氣促1年,患者于1年前于感冒后出現(xiàn)活動后氣緊，經(jīng)自服感冒藥后好轉(zhuǎn)。后多次于受涼后發(fā)生活動后氣緊，并逐漸出現(xiàn)雙下肢水腫，經(jīng)當?shù)蒯t(yī)院（具體不祥）治療后好轉(zhuǎn)。后多次于勞累或感冒后復發(fā)。為求進一步診治，而于我院就診?；疾∫詠?，精神較差，飲食不佳，小便有所減少。既往有長期大量飲酒史,T：36.3℃ P：85次/分，R：22次/分 BP：120/78 mmHg 氧飽和度

2、：92%端坐位，呼吸急促。頸靜脈充盈，肝頸征陽性。雙肺中下份濕鳴明顯，較對稱，未聞及干鳴音。心界叩診不清，似有明顯長大，心率120次/分，余心臟聽診不理想。腹軟，肝界長大，肋下2cm肝下5cm。雙下肢水腫,常規(guī)及生化檢查基本正常冠脈造影基本正常,治療所選擇的藥物,地高辛BB （美托洛爾）ACEI （蒙諾）ARB （代文）氫氯噻嗪安體舒通長效硝酸鹽制劑肼苯噠嗪曲美他嗪（萬爽力）輔酶Q10,速尿硝酸甘油硝普鈉多巴

3、胺多巴酚丁胺氨力農(nóng)米力農(nóng),治療最基本的藥物,氫氯噻嗪ACEI or ARBBB 美托洛爾安體舒通地高辛,I 類,答案似乎很簡單，在不能耐受ACEI后可以選擇ARB,但臨床永遠不會那么簡單,從未使用過ARB和ACEI的心衰患者，是否必須經(jīng)過ACEI，不能耐受才換為ARB？已經(jīng)在使用ARB的心衰患者，是否應(yīng)該換為ACEI？已經(jīng)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適合使用ARB？,從未使用過AR

4、B和ACEI的心衰患者，是否必須經(jīng)過ACEI，不能耐受才換為ARB？,ACEI vs ARB,VALIANT 研究設(shè)計,N=14703,急性心肌梗死（0.5-10天），合并心力衰竭的臨床/放射影像學證據(jù)和/或左室收縮功能障礙,主要終點：全因死亡率次要終點：心血管死亡、心力衰竭住院、心肌梗塞復發(fā),,平均隨訪時間：24.7月事件驅(qū)動,卡托普利50mg tid（n=4909）,纈沙坦 160mg Bid（n=4909）,卡托普利50m

5、g tid+ 纈沙坦 80mg Bid（n=4885）,隨機、雙盲、活性藥對照,,,,,,死亡率和聯(lián)合終點比較,至少纈沙坦不比卡托普利差,,,OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan,,,DesignMulticenter, multinational, randomized, double-

6、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 endpoint

7、Primary 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),,,OPTIMA

8、AL: 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,

9、Dickstein et al. Lancet 2002; 360:752–60.,,,,,,,OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan- RESULTS continued -,,,Months after randomization,Endpoint,rate (%),0,0,,,,6,,12,

10、,18,,24,,30,,36,,,,,Secondary and tertiary endpoints,Dickstein et al. Lancet 2002; 360:752–60.,RR 1.19(95% CI 0.98–1.43),P = 0.072,Captopril,Losartan,,,0,,,,,,,,,,,,5,,10,,15,,5,,10,,15,Sudden cardiac death or cardiac a

11、rrest,RR 1.03(95% CI 0.89–1.18),P = 0.72,Reinfarction,,,,,,,,,OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan- RESULTS continued -,,,Months after randomization,Hospitalization,

12、(%),0,0,,,,6,,12,,18,,24,,30,,36,,,,20,,40,,60,,80,,All-cause hospitalization,,,,Dickstein et al. Lancet 2002; 360:752–60.,,,OPTIMAAL: Optimal Trial In Myocardial Infarction with the Angiotensin Antagonist Losartan- SUM

13、MARY -,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 inhibitor

14、s therefore remain the first-choice therapy in this group,RESOLVED結(jié)論：坎地沙坦和卡托普利一樣有效和安全，聯(lián)用對防止左室重構(gòu)比單用任何藥物都有效,ARB在心衰中的作用，部分藥物不劣于ACEI,AHA/ACC 2009 guideline,IIa Angiotensin II receptor blockers are reasonable to use as a

15、lternatives to ACE inhibitors as first-line therapy for patients with mild to moderate HF and reduced LVEF,已經(jīng)在使用ARB的心衰患者，是否應(yīng)該換為ACEI？,已經(jīng)使用ACEI的心衰患者，是否可以加用ARB？,纈沙坦 vs 安慰劑,絕大多數(shù)都在服用ACEI,生存率沒有差別,事件發(fā)生率纈沙坦組明顯為低,纈沙坦與ACEI聯(lián)用降低事件發(fā)生

16、率但不應(yīng)該與ACEI及BB聯(lián)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

17、 Reduction in Mortality and morbidity (CHARM)-Added,Randomized, double-blindNYHA class II–IV, LVEF ≤40%, stable ACEI dose for ≥30 daysN = 2548,Candesartan 32 mg qdn = 1276,Placebo n = 1272,Median follow-up: 41 months

18、,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

19、.,Recommended dose of ACEICHARM prespecifiedMaximum dose of ACEIFDA 2005CHARM-AddedCHARM-AlternativePooled results (low LVEF patients),NoYesNoYes,125712912019529254820284576,0.26 0.29,Patients (n),Cand

20、esartan better,Placebo better,P value for interaction,,,,,,,,,0.6,0.8,1,1.2,Hazard ratio (95% Cl),,,,,,,,,,,,,CHARM-Added 結(jié)論,坎地沙坦降低心血管死亡及事件發(fā)生率，無論是否使用ACEI，而且在高劑量ACEI病人中都有好處聯(lián)用坎地沙坦相較單獨使用ACEI，有更大的益處。,McMurray JJV et al. Am

21、Heart J. 2006;151:985-91.,是否每一個心衰患者，都要ARB+ACEI聯(lián)用？,2008 ESC 指南確定為I類適應(yīng)證,ONTARGET：概述,ONTARGET：雷米普利 vs. 雷米普利＋替米沙坦主要終點無顯著差異,,替米沙坦雷米普利替米沙坦+雷米普利,隨訪時間（年）,累積事件發(fā)生率（%）,ONTARGET 總結(jié),Telmisartan vs. Ramipril主要終點：非劣于雷米普利低血壓發(fā)生率顯

22、著高于雷米普利Telmisartan plus Ramipril vs. Ramipril聯(lián)合治療未較單藥帶來更多收益聯(lián)合治療不良事件發(fā)生率更高：低血壓、腎功能不全,,Meta-analysis: Combined therapy with ACE inhibitors and ARBs vs ACE-inhibitor therapy alone in patients with heart failure,Kuenzli A

23、. European Society of Cardiology 2009 Congress; August 30-September 2, 2009; Barcelona, Spain.,沒有絕對的真理細分病人群才是硬道理,EF值很低，靜脈使用多巴酚丁胺,LVEF 25% 26%,是否所有的心衰都應(yīng)該使用ARB？,瓣膜病心衰舒張性心衰,舒張性心衰,總結(jié),ARB在心衰治療中有重要作用，部分藥物與ACEI的益處可能相當ARB與AC