急性心衰治疗若干进展

,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,急性心衰治疗若干进展,急性心衰治疗若干进展急性心衰治疗若干进展内 容ASCEND-HF,DOSE,书籍能培养我们的道德情操，给我们巨大的精神力量，鼓舞我们前进,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 years,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,ESC2005,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 Nesiritide 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 alone.,The Hospitalized Patient,Severe Symptomatic Fluid Overload,New,I,IIa,IIb,III,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 chronic 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 (%),311,4/29 (14),15/74 (20),325,2/42 (5),15/85 (18),326,9/102 (9),36/203 (18),VMAC,45/216 (21),74/273 (27),Precedent,9/83 (11),29/162 (18),Totals,69/472 (15),169/797 (21),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 Fixed-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 Clinic,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 NOT ALLOWED AT ANY TIME!,Randomized to,1 of 2,Groups,N=7141,Nesiritide,plus,standard of care,首先给予其静脉注射负荷剂量的奈西立肽,，,然后持续静脉滴注,24 h,，共给药,7,天,Placebo,plus,standard of care,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 of 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;74:1303,1306,.,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 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 (such 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,液体潴留,利尿剂,日剂量,（,mg,）,注释,中度,速尿,布美它尼,托拉塞米,20-40,0.5-1,10-20,根据临床症状口服或静注，根据临床反应调整滴定速度，监测血钾、血钠、血肌酐及血压。,严重,速尿,速尿滴注,布美它尼,托拉塞米,40-100,5-40mg/h,1-4,20-100,静注增加剂量,优于高冲击剂量,口服或静注,口服,绊利尿剂抵抗,加双氢克尿噻,或美托拉宗,或,螺内酯,50-100,2.5-10,25-50,联合用药优于高剂量髓绊利尿剂,，肌酐清除率,30ml/min,时双氢克尿噻效果更佳；,无肾衰或血钾正常或偏低时螺内酯是最佳选择 。,碱中毒,乙酰唑氨,0.5mg,静注,袢利尿剂及噻嗪类利尿剂抵抗,增加多巴胺或多巴酚丁胺,合并肾衰或低血钠考虑使用超滤或血透,Diuretic Optimization Strategies Evaluation in Acute Heart Failure,(DOSE),G. Michael Felker, MD, MHS, FACC,Christopher 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 bolus,Continuous infusion,Dosing,Low intensification (,过去日剂量,),High intensification (,过去日剂量的倍,),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,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),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),ACC2010,N Engl J Med 2011;364:797-805,Secondary Endpoints:Low vs. High Intensification,Low,High,P value,Dyspnea VAS AUC at 72 hours,4478,4668,0.041,% free from congestion at 72 hrs,11%,18%,0.091,Change in weight at 72 hrs,-6.1 lbs,-8.7 lbs,0.011,Net volume loss at 72 hrs,3575 mL,4899 mL,0.001,Change in NTproBNP at 72 hrs (pg/mL),-1194,-1882,0.06,% Treatment failure,37%,40%,0.56,Length of stay, days (median),6,5,0.55,ACC2010,N Engl J Med 2011;364:797-805,死亡、心衰再住院或再进急诊室的复合终点,两种给药方式、两种剂量的比较,N Engl J Med 2011;364:797-805,Change in Creatinine at 72 hours,Q12Continuous,p = 0.45,0,Change in Creatinine (mg/dL),Low High,ACC2010,N Engl J Med 2011;364:797-805,对,DOSE,研究的评价,该研究结果可能会改变目前的临床实践,许多临床医生可能会倾向于选择能够更快缓解呼吸困难的大剂量治疗方案,另外，由于推注的效果与连续输注的效果相当，因此临床医生可能会选择更方便的推注治疗方案,研究的局限性,DOSE,入选的患者均为慢性心衰急性发作,DOSE,样本量较小，不足以检测各组之间发生临床事件的差异,DOSE,方案允许分组治疗,48hr,后根据患者临床反应调整治疗方案，这就限制了对各组疗效终点差异的观察,Thank you very much!,患者基本特征,患者基本特征,人有了知识，就会具备各种分析能力，,明辨是非的能力。,所以我们要勤恳读书，广泛阅读，,古人说“书中自有黄金屋。,”通过阅读科技书籍，我们能丰富知识，,培养逻辑思维能力；,通过阅读文学作品，我们能提高文学鉴赏水平，,培养文学情趣；,通过阅读报刊，我们能增长见识，扩大自己的知识面。,有许多书籍还能培养我们的道德情操，,给我们巨大的精神力量，,鼓舞我们前进,。,