急性心衰治疗若干进展ppt课件

1、.,急性心力衰竭药物治疗的 若干进展,2011.4,.,内 容,ASCEND-HF DOSE,.,急性失代偿性心衰的预后,Median length of hospital stay: 6 days Hospital readmissionsHospital readmissions 20% at 30 days20% at 30 days 50% at 6 months50% at 6 months MortalityMortality 11.6% at 30 days11.6% at 30 days 33.1% at 12 months 50% at 5 years50% at 5 yea

2、rs,Rev Cardiovasc Med. 2002;3(suppl 4) Arch Intern Med. 2002;162Intern Med. 2002;162,.,Acute heart failure with systolic dysfunction,Furosemide+/- Vasodilator,SBP100 mmHg,SBP 85-100 mmHg,SBP 5ug/kg/min,No response: Reconsider mechanistic therapy inotropic agents,Good response: Oral therapy ACEI,ESC2

3、005急性心衰诊断和治疗指南,.,ADHF的药物治疗终于取得了一些进展,在过去30年中，急性失代偿性心衰（ADHF）的药物治疗几乎没有进展 ADHF治疗新药乏善可陈 在不同医院和不同医生之间利尿剂的应用剂量和应用方式均大相径庭，缺乏安全性和有效性的高质量研究 终于有些进展 ASCEND-HF（AHA 2010) DOSE最新结果（N Engl J Med 3月3号在线）,.,奈西立肽(Nesiritide，人类BNP) 一种激素样物质，除扩张动脉和静脉外，还可促进利钠利尿 降低患者左室充盈压和呼吸困难程度，缓解症状 FDA approved 2001,.,The Effects of Nesi

4、ritide on Neurohormones,.,In patients with evidence of severely symptomatic fluid overload in the absence of systemic hypotension, vasodilators such as intravenous nitroglycerin, nitroprusside or neseritide can be beneficial when added to diuretics and/or in those who do not respond to diuretics alo

5、ne.,The Hospitalized Patient,Severe Symptomatic Fluid Overload,New,A Report of the ACCF/ AHA Task Force on Practice Guidelines,.,BNP可用于治疗急性心衰，患者的体征为肺充血/水肿，BP 90mmHg 静注BNP时，其输注速率从0.015到0.03 ug/kg/min均可，无论开始是否进行负荷推注（2ug/kg）。不推荐和其他静注血管扩张剂联用,ESC Guidelines for the diagnosis and treatment of acute and ch

6、ronic heart failure 2008,.,5个研究的荟萃分析：奈西立肽对肾功能影响,Control, n/N (%),Nesiritide, n/N (%),study,肾功能恶化的定义：SCr0.5 mg/dL.,Circulation. 2005;111:1487-1491,.,Mortality Within 30 Days of Treatment Associated With Nesiritide or Control Therapy With Overall Risk Ratio Calculated by Mantel-Haenszel Test Using a F

7、ixed-Effects Model.,Sackner-Bernstein, J. D. et al. JAMA 2005;293:1900-1905,Copyright restrictions may apply.,荟萃3个小规模 试验： NSGET VMAC PROACTION,.,ASCEND-HF 奈西立肽治疗失代偿性心衰患者 临床疗效的短期研究,Duke Heart Failure Research Pager: 970-0736,.,NHLBI Heart Failure Clinical Research Network,Baylor Duke Harvard Mayo Cli

8、nic Minnesota Montreal Morehouse Utah Vermont,.,Purpose,在常规治疗基础上，通过双盲安慰剂对照研究评价奈西立肽对于急性代偿性心衰患者的疗效和安全性. Double blinded study meaning subjects, MD, and research team are unaware of what treatment is being received.,.,.,入选标准,静息时呼吸困难 肺淤血,入院24小时内存在心衰的症状和体征,.,Interventions,USE OF OPEN LABEL NESIRITIDE IS N

9、OT ALLOWED AT ANY TIME!,.,Why 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?,复合主要终点,.,Nursing Roles,在治疗6小时和24 小时填写问卷表* 和VAS量表 问卷表和VAS量表内容包括: 自我评价呼吸困难程度 健康状态/一般情况, 自我护理 能力, 疼

10、痛, 抑郁, 体力 7级评定 *Found in patients chart box.,.,.,.,30天复合终点,.,30天复合终点的亚组分析,.,肾脏安全性,.,对ASCEND-HF评价,ASCEND-HF研究澄清了既往质疑，证实奈西立肽安全 ASCEND-HF研究在给药方案上可能存在问题：由于奈西利肽的有效半衰期比硝酸甘油和硝普钠长，因此其副作用的持续时间可能较长, 低血压的发生率相对高 采用保守（即无负荷量）和推荐剂量治疗可减少并发症,.,内 容,ASCEND-HF DOSE,.,Diuretics and Heart Failure,Diuretics are mainstay o

11、f therapy for acute heart failure (given to 90% of pts in ADHERE) Relieve symptoms of dyspnea and edema in most patients Associated with variety of problems: Electrolyte abnormalities Activation of RAAS and SNS Diuretic resistance Increased mortality?,.,Diuretics and PCWP,Circulation. 1986;74:130313

12、06.,.,.,速尿静推40-100mg,强心,.,If patients are already receiving loop diuretic therapy, the initial intravenous dose should equal or exceed their chronic oral daily dose. (Level of Evidence: C).,The Hospitalized Patient,Treatment With Intravenous Loop Diuretics,New,A Report of the ACCF/ AHA Task Force on

13、 Practice Guidelines,.,The Hospitalized Patient,Intensifying the Diuretic Regimen,New,When 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 (s

14、uch as metolazone, spironolactone or intravenous chlorthiazide) or c. Continuous infusion of a loop diuretic.,A Report of the ACCF/ AHA Task Force on Practice Guidelines,.,急性心衰患者利尿剂使用的指征及剂量,.,Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE),G. Michael Felker, MD, MHS, FACC C

15、hristopher M. OConnor, MD, FACC on behalf of the NHLBI Heart Failure Clinical Research Network,利尿剂优化策略治疗急性心衰评价,ACC2010 N Engl J Med 2011;364:797-805,.,Aims,To evaluate the safety and efficacy of various initial strategies of furosemide therapy in patients with ADHF Route of administration: Q12 hours

16、 bolus Continuous infusion Dosing Low intensification (过去日剂量) High intensification (过去日剂量的2.5倍),ACC2010 N Engl J Med 2011;364:797-805,允许48hr后根据患者临床反应调整治疗方案,.,Acute Heart Failure (1 symptom AND 1 sign) 24 hours after admission 308例,2x2 factorial randomization,Low Dose (1 x oral) Q12 IV bolus,48 hours

17、,1) Change to oral diuretics 2) continue current strategy 3) 50% increase in dose,Co-primary endpoints,High Dose (2.5 x oral) Q12 IV bolus,Low Dose (1 x oral) Continuous infusion,High Dose (2.5 x oral) Continuous infusion,72 hours,Study Design,Clinical endpoints,60 days,.,主要终点,主要疗效终点： 基线至72 h内患者对症状的

18、总体自评 次要疗效终点 呼吸困难、体重变化、体液净损失、受充血影响的患者比例、肾功能恶化、心力衰竭恶化,.,Patient Global Assessment VAS AUC: Q12 vs. Continuous,Pt Global Assessment by VAS,Q12 VAS AUC, mean (SD) = 4236 (1440) Continuous VAS AUC, mean (SD) = 4373 (1404) P = 0.47,Q12,Continuous,Hours,ACC2010 N Engl J Med 2011;364:797-805,.,Patient Global Assessment VAS AUC: Low vs. High Intensification,Hours,Pt Global Assessment by VAS,Low,High,Low VAS AUC, mean (SD) = 4171 (1436) High VAS AUC, mean (SD) = 4430 (1401) P = 0.06,ACC2010 N Engl