心力衰竭臨床藥物治療面臨挑戰(zhàn)會(huì)議課件教學(xué)幻燈PPT

1、李 勇復(fù)旦大學(xué)華山醫(yī)院心臟科心力衰竭臨床藥物治療面臨的挑戰(zhàn)acute infarction(hours)infarct expansion(hours to days)global remodeling(days to months)心肌梗死后左心室重構(gòu)交感神經(jīng)raas交感神經(jīng)raas交感神經(jīng)raas功能acei治療心力衰竭治療心力衰竭病死率和病殘率病死率和病殘率0 05 5101015152020252530303535404045455050危險(xiǎn)度降低（）危險(xiǎn)度降低（）心衰死亡率心衰死亡率或住院率或住院率總死亡率總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.-阻滯劑治療心力衰竭：無(wú)可辯駁的證據(jù)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風(fēng)險(xiǎn)比值 0.85 (95% ci 0.75-0.96), p=0.011校正風(fēng)險(xiǎn)比值 0.85, p=0.010483 (37.9%)538 (42.3%)%nnt = 231 年 hr 0.76p0.001charm - 合用組：首要終點(diǎn)合用組：首要

5、終點(diǎn)心血管死亡或心衰住院的比例(%)安慰劑安慰劑坎地沙坦坎地沙坦有危險(xiǎn)的例數(shù)有危險(xiǎn)的例數(shù)坎地沙坦坎地沙坦127611761063948457安慰劑安慰劑12721136101390642210心率：心血管死亡的預(yù)測(cè)因子心率：心血管死亡的預(yù)測(cè)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風(fēng)險(xiǎn)率風(fēng)險(xiǎn)率 = 1.34 (1.10 1.63)時(shí)間（年）時(shí)間（年）00.511.52051015*change in heart rate and chf mortal

6、ity總死亡率總死亡率隨訪月百分比036912151820151050安慰劑美托洛爾p = 0.0096降低危險(xiǎn) = 44%安慰劑美托洛爾p = 0.0067降低危險(xiǎn) = 36%百分比低劑量組低劑量組每每3 3個(gè)月隨訪個(gè)月隨訪 (n=1016)高劑量組高劑量組每每3 3個(gè)月隨訪個(gè)月隨訪 (n=2635)隨訪月merit-hf: 3個(gè)月后劑量相關(guān)的回顧性亞組分析個(gè)月后劑量相關(guān)的回顧性亞組分析201510500369121518wikstrand j et al. for the merit-hf study group. 4周 (41mg)6周 (80mg)8周 (151mg)基線基線2周 (2

7、1mg)2周 (17mg)4周 (32mg)6周 (64mg)8周與 3月 (76mg)(次/分)美托洛爾控釋片劑量6570758085050100150200merit-hf: 3個(gè)月后劑量相關(guān)的回顧性亞組分析個(gè)月后劑量相關(guān)的回顧性亞組分析3 月 (192mg)小劑量組小劑量組大劑量組大劑量組wikstrand j et al. for the merit-hf study group. 心率減慢 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年齡段平均年齡美國(guó) (chs)芬蘭(helsinki)英國(guó)(poole)丹麥. (copen.)西班牙 (asturias)葡萄牙(epica)荷蘭 (rotter.)瑞典(vasteras)左心室收縮功能降低的比例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患病趨勢(shì) owan te et al. n engl j med. 2006;355:251-259.shf與hf-pef的預(yù)后(5年生存率)owan te et al. n en

12、gl j med 2006; 355: 251-259危險(xiǎn)病例數(shù)危險(xiǎn)病例數(shù)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: 血漿去甲腎上腺素水平與病死率的關(guān)系累計(jì)死亡率累計(jì)死亡率(%)(%)月月ne 900pg/mlne 900pg/mlne 600-900ne 600-900 ne600pg/mlne600pg/ml10080604020001224364860總總 體體p0.0001bnp(pg/ml)238bn

17、p隨機(jī)化后時(shí)間隨機(jī)化后時(shí)間 (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基線四分法全因死亡率亞組分析基線四分法全因死亡率亞組分析201030040anand is. circulation. 2003;107:12781283.隨機(jī)化后時(shí)間隨機(jī)化后時(shí)間 (月月)heart failure after mi and htnsystolic vs d

18、iastolicn engl j med 2003;348:2007-18高血壓-左心室肥厚-交感神經(jīng)活性高血壓交感神經(jīng)活性raas活性心率 x 每搏量 = 心輸出量心肌細(xì)胞肥大，細(xì)胞外基質(zhì)堆積心輸出量左心室壁肥厚，室腔容積減小每搏量舒張時(shí)間間期縮短每搏量藥物對(duì)腎素血管緊張素系統(tǒng)的作用藥物對(duì)腎素血管緊張素系統(tǒng)的作用血管緊張素原血管緊張素原腎素腎素ang iat1 受體受體ang iiaceiarbbbacei (yes) bb (yes)ang ii (fmol/ml)(n = 11)acei (yes) bb (no)(n = 11)101510201510095ang i (fmol/ml)510201510095血管緊張素血管緊張素 ii 血管緊張素血管緊張素 i105105acei + bb 在心力衰竭患者中顯著降低在心力衰竭患者中顯著降低ang ii 水平水平00campbell dj et al. lancet. 2001;358:16091610.腎上腺素系統(tǒng)腎上腺素系統(tǒng)活化活化腎素