1、急性心力衰竭藥物治療的若干進展 2011.4急性心力衰竭藥物治療的若干進展內 容ASCEND-HFDOSE內 容ASCEND-HF急性失代償性心衰的預后 Median length of hospital stay: 6 daysHospital readmissionsHospital readmissions 20% at 30 days20% at 30 days 50% at 6 months50% at 6 monthsMortalityMortality 11.6% at 30 days11.6% at 30 days 33.1% at 12 months 50% at 5 yea

2、rs50% at 5 yearsRev Cardiovasc Med. 2002;3(suppl 4) Arch Intern Med. 2002;162Intern Med. 2002;162急性失代償性心衰的預后 Median length of hAcute heart failure with systolic dysfunction Furosemide+/- VasodilatorSBP100 mmHgSBP 85-100 mmHgSBP 5ug/kg/minNo response:Reconsider mechanistic therapyinotropic agentsGood

3、 response:Oral therapyACEIESC2005急性心衰診斷和治療指南 FurosemiADHF的藥物治療終于取得了一些進展在過去30年中，急性失代償性心衰（ADHF）的藥物治療幾乎沒有進展 ADHF治療新藥乏善可陳在不同醫院和不同醫生之間利尿劑的應用劑量和應用方式均大相徑庭，缺乏安全性和有效性的高質量研究終于有些進展ASCEND-HF（AHA 2010)DOSE最新結果（N Engl J Med 3月3號在線）ADHF的藥物治療終于取得了一些進展在過去30年中，急性失代奈西立肽(Nesiritide，人類BNP) 一種激素樣物質，除擴張動脈和靜脈外，還可促進利鈉利尿降低患者

4、左室充盈壓和呼吸困難程度，緩解癥狀 FDA approved 2001奈西立肽(Nesiritide，人類BNP) The Effects of Nesiritide on NeurohormonesThe Effects of Nesiritide on In patients with evidence of severely symptomatic fluid overload in the absence of systemic hypotension, vasodilators such as intravenous nitroglycerin, nitroprusside or n

5、eseritide can be beneficial when added to diuretics and/or in those who do not respond to diuretics alone.The Hospitalized Patient Severe Symptomatic Fluid OverloadNewIIIaIIbIIIA Report of the ACCF/ AHA Task Force on Practice GuidelinesIn patients with evidence of sBNP可用于治療急性心衰，患者的體征為肺充血/水腫，BP 90mmH

6、g靜注BNP時，其輸注速率從0.015到0.03 ug/kg/min均可，無論開始是否進行負荷推注（2ug/kg）。不推薦和其他靜注血管擴張劑聯用 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008BNP可用于治療急性心衰，患者的體征為肺充血/水腫，BP 5個研究的薈萃分析：奈西立肽對腎功能影響Control, n/N (%) Nesiritide, n/N (%) 3114/29 (14)15/74 (20)3252/42 (5)15/85 (18)3269/102 (9

7、)36/203 (18)VMAC45/216 (21)74/273 (27)Precedent9/83 (11)29/162 (18)Totals69/472 (15)169/797 (21)study腎功能惡化的定義：SCr0.5 mg/dL. Circulation. 2005;111:1487-1491 5個研究的薈萃分析：奈西立肽對腎功能影響Control, nMortality Within 30 Days of Treatment Associated With Nesiritide or Control Therapy With Overall Risk Ratio Calcul

8、ated by Mantel-Haenszel Test Using a Fixed-Effects Model.Sackner-Bernstein, J. D. et al. JAMA 2005;293:1900-1905Copyright restrictions may apply.薈萃3個小規模試驗：NSGETVMACPROACTIONMortality Within 30 Days of TrASCEND-HF奈西立肽治療失代償性心衰患者臨床療效的短期研究Duke Heart Failure ResearchPager: 970-0736ASCEND-HF奈西立肽治療失代償性心衰患者

9、臨床療效NHLBI Heart Failure Clinical Research NetworkBaylorDukeHarvardMayo ClinicMinnesotaMontrealMorehouseUtahVermontNHLBI Heart Failure Clinical Purpose在常規治療基礎上，通過雙盲安慰劑對照研究評價奈西立肽對于急性代償性心衰患者的療效和安全性. Double blinded study meaning subjects, MD, and research team are unaware of what treatment is being rece

10、ived.Purpose在常規治療基礎上，通過雙盲安慰劑對照研究評價奈急性心衰治療若干進展課件入選標準靜息時呼吸困難肺淤血 入院24小時內存在心衰的癥狀和體征 入選標準靜息時呼吸困難入院24小時內存在心衰的癥狀和體征 InterventionsRandomized to1 of 2 GroupsN=7141Nesiritide plus standard of care首先給予其靜脈注射負荷劑量的奈西立肽，然后持續靜脈滴注24 h，共給藥7天Placebo plusstandard of careUSE OF OPEN LABEL NESIRITIDE IS NOT ALLOWED AT AN

11、Y TIME!InterventionsRandomized toNesiWhy is this study being done?Does Nesiritide decrease re-hospitalization or death in 30 days? Does Nesiritide decrease symptoms of dyspnea at 6 and 24 hrs after drug initiated? 復合主要終點Why is this study being done?復Nursing Roles在治療6小時和24 小時填寫問卷表* 和VAS量表問卷表和VAS量表內容包

12、括:自我評價呼吸困難程度健康狀態/一般情況, 自我護理 能力, 疼痛, 抑郁, 體力7級評定*Found in patients chart box.Nursing Roles在治療6小時和24 小時填寫問卷表急性心衰治療若干進展課件急性心衰治療若干進展課件30天復合終點30天復合終點30天復合終點的亞組分析30天復合終點的亞組分析腎臟安全性腎臟安全性對ASCEND-HF評價ASCEND-HF研究澄清了既往質疑，證實奈西立肽安全 ASCEND-HF研究在給藥方案上可能存在問題：由于奈西利肽的有效半衰期比硝酸甘油和硝普鈉長，因此其副作用的持續時間可能較長, 低血壓的發生率相對高采用保守（即無負荷

13、量）和推薦劑量治療可減少并發癥 對ASCEND-HF評價ASCEND-HF研究澄清了既往質疑內 容ASCEND-HFDOSE內 容ASCEND-HFDiuretics and Heart FailureDiuretics are mainstay of therapy for acute heart failure (given to 90% of pts in ADHERE)Relieve symptoms of dyspnea and edema in most patientsAssociated with variety of problems:Electrolyte abnormal

14、itiesActivation of RAAS and SNSDiuretic resistanceIncreased mortality?Diuretics and Heart FailureDiuDiuretics and PCWPCirculation. 1986;74:13031306.Diuretics and PCWPCirculation.急性心衰治療若干進展課件速尿靜推40-100mg 強心速尿靜推40-100mg 強心If patients are already receiving loop diuretic therapy, the initial intravenous

15、 dose should equal or exceed their chronic oral daily dose. (Level of Evidence: C). The Hospitalized Patient Treatment With Intravenous Loop DiureticsNewA Report of the ACCF/ AHA Task Force on Practice GuidelinesIf patients are already receivThe Hospitalized Patient Intensifying the Diuretic Regimen

16、NewWhen diuresis is inadequate to relieve congestion, as evidence by clinical evaluation, the diuretic regimen should be intensified using either:a. higher doses of loop diuretics;b. addition of a second diuretic (such as metolazone, spironolactone or intravenous chlorthiazide) orc. Continuous infus

17、ion of a loop diuretic.A Report of the ACCF/ AHA Task Force on Practice GuidelinesThe Hospitalized Patient Inten急性心衰患者利尿劑使用的指征及劑量液體潴留 利尿劑 日劑量（mg） 注釋 中度速尿布美它尼 托拉塞米20-40 0.5-110-20 根據臨床癥狀口服或靜注，根據臨床反應調整滴定速度，監測血鉀、血鈉、血肌酐及血壓。嚴重速尿速尿滴注布美它尼托拉塞米40-1005-40mg/h 1-4 20-100 靜注增加劑量優于高沖擊劑量口服或靜注口服絆利尿劑抵抗 加雙氫克尿噻或美托拉宗或

18、螺內酯50-100 2.5-1025-50聯合用藥優于高劑量髓絆利尿劑，肌酐清除率30ml/min時雙氫克尿噻效果更佳； 無腎衰或血鉀正常或偏低時螺內酯是最佳選擇 。堿中毒 乙酰唑氨 0.5mg 靜注袢利尿劑及噻嗪類利尿劑抵抗 增加多巴胺或多巴酚丁胺合并腎衰或低血鈉考慮使用超濾或血透急性心衰患者利尿劑使用的指征及劑量液體潴留 利尿劑 日劑量（Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE)G. Michael Felker, MD, MHS, FACCChristopher M. OConnor,

19、 MD, FACCon behalf of theNHLBI Heart Failure Clinical Research Network利尿劑優化策略治療急性心衰評價 ACC2010 N Engl J Med 2011;364:797-805 Diuretic Optimization StrategiAimsTo evaluate the safety and efficacy of various initial strategies of furosemide therapy in patients with ADHFRoute of administration:Q12 hours

20、 bolusContinuous infusion DosingLow intensification (過去日劑量)High intensification (過去日劑量的2.5倍)ACC2010 N Engl J Med 2011;364:797-805 允許48hr后根據患者臨床反應調整治療方案AimsTo evaluate the safety andAcute Heart Failure (1 symptom AND 1 sign)24 hours after admission 308例 2x2 factorial randomizationLow Dose (1 x oral)Q

21、12 IV bolus48 hours1) Change to oral diuretics2) continue current strategy3) 50% increase in doseCo-primary endpointsHigh Dose (2.5 x oral)Q12 IV bolusLow Dose (1 x oral)Continuous infusionHigh Dose (2.5 x oral)Continuous infusion72 hoursStudy DesignClinical endpoints60 daysAcute Heart Failure (1 sy

22、mptom主要終點 主要療效終點： 基線至72 h內患者對癥狀的總體自評次要療效終點呼吸困難、體重變化、體液凈損失、受充血影響的患者比例、腎功能惡化、心力衰竭惡化 主要終點 主要療效終點： Patient Global Assessment VAS AUC:Q12 vs. ContinuousPt Global Assessment by VASQ12 VAS AUC, mean (SD) = 4236 (1440)Continuous VAS AUC, mean (SD) = 4373 (1404)P = 0.47Q12ContinuousHoursACC2010 N Engl J Med

23、2011;364:797-805 Patient Global Assessment VAS Patient Global Assessment VAS AUC:Low vs. High IntensificationHoursPt Global Assessment by VASLowHighLow VAS AUC, mean (SD) = 4171 (1436)High VAS AUC, mean (SD) = 4430 (1401)P = 0.06ACC2010 N Engl J Med 2011;364:797-805 Patient Global Assessment VAS Secondary Endpoints:Low vs. High IntensificationLowHighP valueDyspnea VAS AUC at 72 hours447846680.041% free from congestion at 72 hrs11%18%0.091Change in weight at 72 hrs-6.1 lbs-8.7 lbs0.011Net volume loss at 72 hrs3575 mL4899 mL0.001Change in NTproBNP at 72 hrs (pg/mL)-1194-18820.06% T