心力衰竭临床药物治疗面临挑战会议课件教学幻灯PPT

1、李 勇复旦大学华山医院心脏科心力衰竭临床药物治疗面临的挑战acute infarction(hours)infarct expansion(hours to days)global remodeling(days to months)心肌梗死后左心室重构交感神经raas交感神经raas交感神经raas功能acei治疗心力衰竭治疗心力衰竭病死率和病残率病死率和病残率0 05 5101015152020252530303535404045455050危险度降低（）危险度降低（）心衰死亡率心衰死亡率或住院率或住院率总死亡率总死亡率心衰死亡率心衰死亡率致命性致命性/非致非致命性心梗命性心梗0.0013

2、5% 0.00123% 0.00131% 0.0420% garg r,yusuf s.jama.1995;237:1450-1456.-阻滞剂治疗心力衰竭：无可辩驳的证据34% cumulative mortality (%)days20155010p=.0062 (adjusted)metoprolol cr/xl(n=1990)placebo (n=2001)us carvedilol trials1probability ofevent-free survival carvedilol (n=696)placebo (n=398)daysp.0010.0010020030040065%

3、 1.0merit-hf2survival (% of patients)1009080607006000400300200100dayscarvedilol (n=1156)placebo (n=1133)500600040030020010050035% p=.00013copernicus4days0.02004008001.00.80.6p.000134% bisoprolol (n=1327)placebo (n=1320)cibis-ii30600survival1. packer m et al. n engl j med. 1996;334:13491355.

4、 2. merit-hf study group. lancet. 1999;253:20012007. 3. cibis-ii investigators. lancet. 1999;353:913.4. packer m et al. n engl j med. 2001;344:16511658.70123年年010203040503.5风险比值 0.85 (95% ci 0.75-0.96), p=0.011校正风险比值 0.85, p=0.010483 (37.9%)538 (42.3%)%nnt = 231 年 hr 0.76p0.001charm - 合用组：首要终点合用组：首要

5、终点心血管死亡或心衰住院的比例(%)安慰剂安慰剂坎地沙坦坎地沙坦有危险的例数有危险的例数坎地沙坦坎地沙坦127611761063948457安慰剂安慰剂12721136101390642210心率：心血管死亡的预测因子心率：心血管死亡的预测因子fox k et al. lancet online august 31, 2008. 心率心率 70 bpm心率心率 70 bpm心血管死亡率（心血管死亡率（%）p = 0.0041风险率风险率 = 1.34 (1.10 1.63)时间（年）时间（年）00.511.52051015*change in heart rate and chf mortal

6、ity总死亡率总死亡率随访月百分比036912151820151050安慰剂美托洛尔p = 0.0096降低危险 = 44%安慰剂美托洛尔p = 0.0067降低危险 = 36%百分比低剂量组低剂量组每每3 3个月随访个月随访 (n=1016)高剂量组高剂量组每每3 3个月随访个月随访 (n=2635)随访月merit-hf: 3个月后剂量相关的回顾性亚组分析个月后剂量相关的回顾性亚组分析201510500369121518wikstrand j et al. for the merit-hf study group. 4周 (41mg)6周 (80mg)8周 (151mg)基线基线2周 (2

7、1mg)2周 (17mg)4周 (32mg)6周 (64mg)8周与 3月 (76mg)(次/分)美托洛尔控释片剂量6570758085050100150200merit-hf: 3个月后剂量相关的回顾性亚组分析个月后剂量相关的回顾性亚组分析3 月 (192mg)小剂量组小剂量组大剂量组大剂量组wikstrand j et al. for the merit-hf study group. 心率减慢 incomplete follow-up102 withdrew consent3 randomisationirregularitiesincomplete follow-up114 withd

8、rew consent1 lost to follow-uppatients and follow-up10 917 randomised5479 to ivabradine5438 to placebomedian study duration: 19 months; maximum: 35 months5438 analysed5479 analysed12 138 screenedstudy designivabradine 5 mg 7.5 mg twice dailymatching placebovisits3 yearsam heart j. 2006;152:860-66tre

9、atment target hr60 bpmreduce dosage or discontinue when hr402555-95787675606865年龄段平均年龄美国 (chs)芬兰(helsinki)英国(poole)丹麦. (copen.)西班牙 (asturias)葡萄牙(epica)荷兰 (rotter.)瑞典(vasteras)左心室收缩功能降低的比例hf-psf的比例5551684671593971petrie m, mcmurray j. lancet. 2001;358:423-434. hogg k et al. j am coll card. 2004;43:31

10、7-327.chf患病率患病率 (%)012345678910心力衰竭患者中hf-pef的比例ef50%ef45%ef50%ef50%framingham2(n=73)olmstead1(n=137)chs3 (n=269)nhf project4(n=19,710)1. senni m et al. circulation. 1998;98:2282-2289. 2. vasan rs et al. j am coll card. 1999;33:1948-1955. 3. gottdiener js et al. ann intern med. 2002;137:631-639. ef50

11、%ef 50%owan5(n=4,596)bhatia6(n=2,802)patients (%)4. masoudi fa et al. j am coll card. 2003;41-217-223. 5. owan te et al. n engl j med. 2006;355:251-259. 6. bhatia rs et al. n engl j med. 2006;355:260-269.hf-pef患病趋势 owan te et al. n engl j med. 2006;355:251-259.shf与hf-pef的预后(5年生存率)owan te et al. n en

12、gl j med 2006; 355: 251-259危险病例数危险病例数年年生存率生存率placeboforced titrationmaintenanceenrollmentsingle-blind2 weeksw 2w 4w 8m 6m 10m 14 to endevery 4 months75 mg150 mg300 mgfollow-up continued until 1,440 primary endpoints occurredn=4,128i-preserve: study designirbesartanronly 1/3 pts could enter on an ace

13、irandomized, double-blind, placebo controlled triali-preserve: primary endpointdeath or protocol specified cv hospitalization (mean follow-up 49.5 months)months from randomizationcumulative incidence of primary events (%)40 -0 -10 -20 -30 -061218243642304860542067192918121730164015131291156910884978

14、16206119211808171516181466124615391051446776no. at riskirbesartanplacebohr (95% ci) = 0.95 (0.86-1.05)log-rank p=0.35placeboirbesartani-preserve: baseline treatments3230 lipid lowering59 58 antiplatelet4039 calcium channel blocker5958 beta-blocker1413 digoxin2625 ace-inhibitor1515 spironolactone 828

15、4treatment (%) diureticirbesartan(n = 2067)placebo(n = 2061)38392728total exposed during the study7272adapted with permission from: vasan rs, levy d. arch intern med. 1996;156:1790.progression from hypertensionto lvh, cad, and heart failurehtnsmokinglipidsdiabetesobesitydiabetesinsulin resistancemil

16、vhnormal left ventricular (lv) structureand functionlv remodelingsubclinical lv dysfunctionovert hfdiastolicdysfunctionsystolicdysfunctionchfcadv-heft: 血浆去甲肾上腺素水平与病死率的关系累计死亡率累计死亡率(%)(%)月月ne 900pg/mlne 900pg/mlne 600-900ne 600-900 ne600pg/mlne600pg/ml10080604020001224364860总总 体体p0.0001bnp(pg/ml)238bn

17、p随机化后时间随机化后时间 (月月)生存率生存率2010300400.81.00.99.714.320.732.4% 死亡率死亡率ne572274274394395572ne(pg/ml)0.81.00.924.2% 死亡率死亡率13.816.523.0val-heft: bnp和和ne基线四分法全因死亡率亚组分析基线四分法全因死亡率亚组分析201030040anand is. circulation. 2003;107:12781283.随机化后时间随机化后时间 (月月)heart failure after mi and htnsystolic vs d

18、iastolicn engl j med 2003;348:2007-18高血压-左心室肥厚-交感神经活性高血压交感神经活性raas活性心率 x 每搏量 = 心输出量心肌细胞肥大，细胞外基质堆积心输出量左心室壁肥厚，室腔容积减小每搏量舒张时间间期缩短每搏量药物对肾素血管紧张素系统的作用药物对肾素血管紧张素系统的作用血管紧张素原血管紧张素原肾素肾素ang iat1 受体受体ang iiaceiarbbbacei (yes) bb (yes)ang ii (fmol/ml)(n = 11)acei (yes) bb (no)(n = 11)101510201510095ang i (fmol/ml)510201510095血管紧张素血管紧张素 ii 血管紧张素血管紧张素 i105105acei + bb 在心力衰竭患者中显著降低在心力衰竭患者中显著降低ang ii 水平水平00campbell dj et al. lancet. 2001;358:16091610.肾上腺素系统肾上腺素系统活化活化肾素