急性心衰治療若干進(jìn)展課件

1、急性心力衰竭藥物治療的若干進(jìn)展 2011.4內(nèi) 容ASCEND-HFDOSE急性失代償性心衰的預(yù)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 years50% at 5 yearsRev Cardiov

2、asc Med. 2002;3(suppl 4) Arch Intern Med. 2002;162Intern Med. 2002;162Acute heart failure with systolic dysfunction Furosemide+/- VasodilatorSBP100 mmHgSBP 85-100 mmHgSBP 5ug/kg/minNo response:Reconsider mechanistic therapyinotropic agentsGood response:Oral therapyACEIESC2005急性心衰診斷和治療指南ADHF的藥物治療終于取得

3、了一些進(jìn)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(jìn)展 ADHF治療新藥乏善可陳在不同醫(yī)院和不同醫(yī)生之間利尿劑的應(yīng)用劑量和應(yīng)用方式均大相徑庭，缺乏安全性和有效性的高質(zhì)量研究終于有些進(jìn)展ASCEND-HF（AHA 2010)DOSE最新結(jié)果（N Engl J Med 3月3號在線）The Effects of Nesiritide on NeurohormonesIn patients with evidence of severely symptomatic fluid overload in the absence of systemic hypotension, va

4、sodilators 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 OverloadNewIIIaIIbIIIA Report of the ACCF/ AHA Task Force on Practice Guidelines

5、5個(gè)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)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 Mortality Within 30 Days of Treat

6、ment 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;293:1900-1905Copyright restrictions may apply.薈萃3個(gè)小規(guī)模試驗(yàn)：NSGETVMACPROACTIONASCEND-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 Fai

7、lure ResearchPager: 970-0736Purpose在常規(guī)治療基礎(chǔ)上，通過雙盲安慰劑對照研究評價(jià)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 received.InterventionsRandomized to1 of 2 GroupsN=7141Nesiritide plus standard of care首先給予其靜脈注射負(fù)荷劑量的奈西立肽，然后持續(xù)靜脈滴注24 h，共

8、給藥7天Placebo plusstandard of careUSE OF OPEN LABEL NESIRITIDE IS NOT 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? 復(fù)合主要終點(diǎn)Nursing Roles在治療6小時(shí)和24 小時(shí)填寫問卷

9、表* 和VAS量表問卷表和VAS量表內(nèi)容包括:自我評價(jià)呼吸困難程度健康狀態(tài)/一般情況, 自我護(hù)理 能力, 疼痛, 抑郁, 體力7級評定*Found in patients chart box.30天復(fù)合終點(diǎn)腎臟安全性對ASCEND-HF評價(jià)ASCEND-HF研究澄清了既往質(zhì)疑，證實(shí)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(xù)時(shí)間可能較長, 低血壓的發(fā)生率相對高采用保守（即無負(fù)荷量）和推薦劑量治療可減少并發(fā)癥 Diuretics and Heart FailureDiuretics are mainstay of

10、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 abnormalitiesActivation of RAAS and SNSDiuretic resistanceIncreased mortality?Diuretics and PCWPCirculation. 1986;74:13031306.速尿靜推40-10

11、0mg 強(qiáng)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 DiureticsNewA Report of the ACCF/ AHA Task Force on Practice GuidelinesTh

12、e Hospitalized Patient Intensifying the Diuretic RegimenNewWhen 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, spironolac

13、tone or intravenous chlorthiazide) orc. 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(jù)臨床癥狀口服或靜注，根據(jù)臨床反應(yīng)調(diào)整滴定速度，監(jiān)測血鉀、血鈉、血肌酐及血壓。嚴(yán)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(yōu)于高沖擊劑量

14、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螺內(nèi)酯50-100 2.5-1025-50聯(lián)合用藥優(yōu)于高劑量髓絆利尿劑，肌酐清除率30ml/min時(shí)雙氫克尿噻效果更佳； 無腎衰或血鉀正常或偏低時(shí)螺內(nèi)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Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE)G. Michael Felker, MD, MHS, FACCChristopher M. OConnor, MD,

15、 FACCon behalf of theNHLBI Heart Failure Clinical Research Network利尿劑優(yōu)化策略治療急性心衰評價(jià) ACC2010 N Engl J Med 2011;364:797-805 AimsTo evaluate the safety and efficacy of various initial strategies of furosemide therapy in patients with ADHFRoute of administration:Q12 hours bolusContinuous infusion DosingLo

16、w 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(jù)患者臨床反應(yīng)調(diào)整治療方案Acute Heart Failure (1 symptom AND 1 sign)24 hours after admission 308例 2x2 factorial randomizationLow Dose (1 x oral)Q12 IV bolus48 hours1) Change to oral diuretics2) continue curren

17、t 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 days主要終點(diǎn) 主要療效終點(diǎn)： 基線至72 h內(nèi)患者對癥狀的總體自評次要療效終點(diǎn)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 Patient Glob

18、al 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 2011;364:797-805 Patient Global Assessment VAS AUC:Low vs. High IntensificationHoursPt Global Assessment by

19、 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 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 h