正確評價β受體阻滯劑在高血壓治療中的一線地位文.

1、正確評價卩受體阻滯劑在高血壓治療中一線藥物的地位SNS在心血管疾病的重要性L壓早期已有SNS激活以色列公務員研究：心率與心肌梗死危險80<01<7171-90>90>1001J0. YOOO-巴 2 次50<6565-7475 84>84不同心率（次分）不同心辛 < 決/分）Medalie JH. et al. J Chronic DisFramingham：心率與死亡率 CHD CVD所有原因Adjusted survival curves for overall mortalityby RHR quintiles1.0-0.9-0.8-0.7-0.

2、6-RHR in quintilies <62 bpm63-70 bpm71-76 bpm77-82 bpm- >83 bpmn=249913FU 14.7 years10*0015.0020*000.5-o.oo 5.60Years after enrolmentFigure 1 adjusted for age, gender, hypertension, diabetes mellitus, cigarette smoking, clinically signified nt coronary vessel, EF, recreational activity, treatm

3、ent with antiplatelets, diuretics, p-blockers, and lipid-lowering drugs RHR. resting heart rate.Ariel Diaz et al. EHJ 2005Adjusted survival curves for Cv mortality by RHR-e>AJns a>o三 EnoRHR in quintilies <62 bpm63-70 bpm71-76 bpm77-82 bpm- >83 bpmn = 24,913FU 14.7 yearsFigure 2heart rate

4、.Asterisk indicates adjusted as Agure 1 plus BMI. CV, cardlovas-cular; RHR, restingAriel Diaz et al. EHJ 2005猝死心理社會應激為觸發(fā)因素Psychosocial Stress and theTriggering of Sudden DeathThe hforthridge EarthquakeJanuary 17,1994, at 4.31 am彷受體阻滯劑的作用機制卩-受體阻滯劑具有無與倫比的心臟保護作用國際高血壓指南P 受體阻滯劑始終是選或一線藥物 0受體阻滯劑的臨床實踐B 阻滯劑的

5、作用機制降低交感神經(jīng)張力 防止兒茶酚胺的心貼毒性作用抑制異常、過度、持續(xù)的神經(jīng)激素活性增高 和RAS間的相互作用：降低血壓 緩解心肌缺血（減少心肌耗氧、冠脈血流有利的重分配）改善心肌重構減慢心率 減少心律失常（包括復雜室性心律失常） 提高心室顫動閾值降低猝死ESC Expert Consensus Document on p-blockers 2004高血壓時交感活性增加ECQ4ay.of«fnate SOmniHg MBHA:32 burMi p«r min 45 bursts per IWhO y alomaioM8NA-42 Dur»H 嚴 minH bur

6、sts (00 2WiMmMSNAuuMsmBP 148/1022 2007 60EH斥審NW 糊時卅*5*BP 107/58»w5e<NS4020!NT肌肉交感興奮去甲腎上腺素釋放增加Schlaish MP Hypertension 2004;43:169高血壓交感活性增加和左心室肥厚的關系左室重昴/交感活性去甲腎上腺素釋放增加Schlaich MP Circulation 2003:108:560高血壓心臟NE和All釋放之間缺乏關系NTEH"0009 p 0.961nt =正常血壓 EH = 發(fā)性高血壓504030202 0I 24681012 14CS Ang

7、iotensin (tmol ml)Schlaish MP Hypertension 2004;43:169原發(fā)性高血壓交感活性增加中樞交感活性輸出增加總體、心臟及腎臟去甲腎上腺素釋放增加肌肉交感張力增加神經(jīng)元去甲腎上腺素重新攝取降低左心室肥厚程度與心臟交感活性相關血管緊張素-11濃度不增加研究結果提示高血壓時交感神經(jīng)系統(tǒng)激活先于腎素一血管緊張素系統(tǒng)激活Slaich MP Hypertension 2004;43:169因此治療高血壓時在阻斷RAS之前阻斷NE活性可能更為合理治療無并發(fā)癥的高血壓患者卩阻滯劑可在ACEI或ARB之前應用卩受體阻滯劑的作用機制 0-受體阻滯劑具有無與倫比的心臟保護

8、作用國際高血壓指南卩受體阻滯劑始終是首選或一線藥物 B受體阻滯劑的臨床實踐咼血壓病的一級預防MAJOR CARDIOVASCULAR EVENTSComparisons of different active treatmentsBPdifferenceFavours(mm Hg)first listedFavourssecond listed| RR (95% Cl)ACEI us. D/BB| I2/0>|1.O2(O.98,1.O7)|CA vs. D/BB| I 1/0ACEI vs CA1/1v6|1.O4 (0.99,1.08)|*0.97 (0.92,1.03)帀叵帀(Re

9、lative RiskCARDIOVASCULAR DEATHComparisons of different active treatmentsBPdifferenceFavoursFavours(mm Hg)c “I 1 n/nfirst listedsecond listedRR (95% Cl)|ACEI vs D/BB| | 2/0 ,<A11.03 (0.95,1.11)CA vs. D/BB| | 1/0o11.05 (0.97,1.13)1ACEI vs. CA1/11.03 (0.94,1.13)Relative RiskBPLT 2003TOTAL MORTALITY

10、Comparisons of different active treatmentsBPdiffere nee(mm Hg)FavoursFavoursfirst listed second listedRR (95% Cl)ACEI us. D/BB| I 2/0 I CAJDBBACEI vs. CA 1/11.00 (0.95105)10.99 (0.95,1.04)：1.04 (0.98,1.10)Relative RiskBPLT 2003Conclusions I Similar net effects on total cardiovascular events of:一 ACE

11、 inhibitors一 Calcium antagonists一 Diuretics/beta-blockers美托洛爾預防高血壓患者動脈粥樣 硬化研究（MAPHY） 3234例男性高血壓患者，40-64y,平均隨訪5.0年總病死率 I 22% （P二0.028）-美托洛爾組4.0% （65/1609例）-利尿劑組5. 1% （83/1625例）與利尿劑組相比，美托洛爾組-心血管猝死J 30% （ P二0.017）-冠心病事件（致死+非致死Z 24% （ P-0.0010）Wikstrand J et al JAMA 1988一級預防一 MAPHY90總死亡率11III 1II510隨訪時間

12、.年70心血管猝死隨訪時間.年Wikstrand J et al JAMA 1988Olsson G et alAm J Hypertens 1991一級預防MAPHY 致死性+非致死性事件(至首次事件發(fā)生時間) 160n冠脈事件140120H10080402°-/>I110一一利尿劑p=0.0010L美托洛爾危險性降低24%卒中事件篁飜爾5隨訪時間，年Wikstrand et al. Hypertension 1991;17;5798810MRC, IPPPSH和MAPHY研究結果薈萃分析10,951例病人隨機分組， 隨訪51,100病人年研究終點非卩阻滯劑1(n=5452)

13、 事件發(fā)£0阻滯劑 (n=5499) 主數(shù)危險性 降低 (%)p值總死亡率24720220%0.023猝死1016438%0.003冠心病(致死32526321%0.006+非致死性)隨機分組1主要為利尿劑Wikstrand et alr In Clinical trials in Hypertension, ed Henry Black, New York, 2001. pp 141-158卡托普利與阿替洛爾：II型糖尿病患者終點事件發(fā)生率比較（UKPDS ）絕對危險（毎1000購人年）卡托普利組臨床終點卡托普利組5=400阿替洛爾組5=358）P值相對危險 （95%可信區(qū)間）任何

14、尿病有關終點53.348.40.431.10(0.86-1.41)糖尿病有關死亡15.212.00.281.27(0.82-1.97)總死亡率23.820.80.441.14(0.81-1.61)心肌梗死20.216.90.351.20(0.82-1.76)中風6.86.10.741.12(0.592.12)外周血管病變1.61.10.591.48(0.35-6.19)澈血管病13.510.40.301.29(0.802.10)UK Prospective Diabetes Study Group. BMJ 1998;317(7160):71320LIFE研究：主要結果 9193例高血壓左室肥

15、厚患者，平均隨訪54個月主要終點（中風/心肌梗死/心血管病死亡）- 氯沙坦組11% vs阿替洛爾組13%（降低 13.0%, p=0.021）二級終點（10項，包括總死亡率）-致死或非致死中風降低24.9% （5% vs 7% p=0.001）-致死或非致死心肌梗死增高7.3% （p=0.49）-心血管病死亡率降低11.4% （p=0.21）Lancet 2002| A SCOT所有終點總結主要終點Non-fatal Ml (incl silent) * fatal CHD 次要終點Non-fatal Ml (exc. Silent) *fatal CHD Total coronary end

16、 point Total CV event and procedures Ail-cause mortality Cardiovascular mortalityFatal and norvfatal stroke Fatal and norvfatal heart failureUnadjusted Hazardratio (95% Cl)0.90 (0.79-1.02)0.87 (0.76-1.00)0.87 (0.79-0.96)0.84 (0.78-0.90)0.89 (0.81-0.99)0.76 (0.65-0.90)0.77 (0.66-0.89)0.84 (0.66-1.05)

17、3級終點Silent Ml Unstable angi na Chronic stable angina P&rlpheral arterial disease Llfe-threatening arrhythmias New-onset diabetes mellltus New-onset renal Impairment事JG分析Primary end point coronary revasc procs CV doath * MU stroko 0.500.701.bo1.27 (0.80-2.00)0.68 (0.51-0.92)0.98 (0.8M.19)0.65 (0.

18、52-0.81)1.07 (0.62-1.85)0.70 (0.63-.078)0.85 (0.75-0.97)0.86 (0.77096)0.84 (0.76-0.92)氨氯地平土培唏普利更好 阿替洛爾士更好The area of the blue square is proportional to the amount of statistical informationonly 14.3% of patients in the amlodipine group and 8.6% in the beta-blocker group remained on monotherapy at th

19、e end of the study, making this a trial of combination regimens Dahlof saidDevereux said"I think the differences should be interpreted as being between regimens rather than between classes of drugs."ASCOT為藥物聯(lián)合方案之間的比較，而非二類藥物之間的比較 一級終點：非致死性Ml和致死性冠心病 二組無差異卩-受體阻滯劑應用的是氨酰心胺The results observed a

20、re not necessarily applicable to all p blockers. They could simply indicate particular disadvantages of the specific drugs usedeg. atenolol as recently suggested.However, pending further information, we believe the combi nation of a B blocker and a diuretic should not be recommended in preferenee to

21、 the comparator regimen used in ASCOT-BPLA for routine use, but only for specific circumstances.Bjorn Dahldf et al in ASCOT-BPLA, LancetAtenol vs placebo in hypertensiontMd»AFaeai<r 12忖/I jftMtVM7PK/Ulvw 14.* m、CUVexfof hr«Ev«<nv«y工"045四 rm，”W4I少10ff ww1V4HMFMS52171?沁

22、9IU91U."IV74114-61IS 71IR3l«2(0-r> 157>JX on zoegumneel>/4SBJ16%ixcn541 M17 01J*JJU> 29 2；183Strokeo8W&> 1211<»A4<v far 1 >«|A741""J3QMortality1H(A2OH»7H 1 ill巧 247呵W劉AMI126 (&I9> 1071 ictffolU 1 Ml“】(!£ 1M)CM W"CV Morta

23、lityCarlberg B Lancet 2004;364:1684Atenolol in hypertension: is ita wise choice?Bo Carlberg, Ola Samuelsson, Lars Hjalmar Lindholm Lancet 2004Hence, based on the results of our meta-analyses and on the effects of atenolol in other cardiovasculardisorders, we have doubts about the suitability of aten

24、olol as a first-line antihypertensive drug and as a reference drug in outcome trials of hypertension.The results observed are not necessarily applicable to all 卩 blockers They could simply indicate particular disadvantages of the specific drugs usedeg. atenolol as recently suggested.However, pending

25、 further information, we believe the combination of a B blocker and a diuretic should not be recommended in pref ere nee to the comparator regime n used in ASCOT-BPLA for routine use, but only for specific circumstances.Bjorn Dahlof et al In ASCOT-BPLA, LancetDr Peter S Sever (Imperial College Londo

26、n, UK) told a press conference here. HWe recognize that there are clearly subgroups of patients in whom beta blockers are indicated :,those with a prior myocardial infarction or symptomatic coronary heart diseaselbut in uncomplicated hypertension, I th泊k the ASCOT data seriously raise questions abou

27、t the future position of beta blockers in the management of hypertension：HWe have reason to believe there may well be an adverse interaction between atenolol, thiazides, and statins and also a potential for beneficial interaction between amlodipine, perindopril, and statins/Effects of combined stati

28、n and beta-blocker treatment onone-year morbidity and mortality after acute myocardialinfarction associated with heart failureA Hoqnestad et al. Am J Cardid 20043:603-6()®ecodpuUJHow to define the“ uncomplicated hypertension 5, ?Importanee of Primary PreventionFramingham HeartStudy (n=5144)Ml o

29、r SD as 1stPresentation0204060Patients (%)Murabito et al Circ 1993 88:2543朝鮮戰(zhàn)爭死亡者300人尸檢平均年齡22.1歲77.3% CAD39%阻塞斑塊ENOS JAMAPrevale nee of Atherosclerosis by Donor Age10Q80-604020185%60%37%17%<20 2029 303940-49 >50Donor Age (years)Tuzcu Circ 199932 Year Old FemaleAtherosclerosis:Change in ApproachEarly intervention payslong term dividends高血壓病早期卩受體阻滯劑的應用？高血壓病早期已有交感神經(jīng)系統(tǒng)的過度激活 卩受體阻滯劑在高血壓病一級預防對心臟的保護作用從未被超越如何識別高血壓病早期T晚期？高血壓病早期仍應及早應用卩受體阻滯劑咼血壓病的二級預防冠心病高危患者心梗后患者心衰患者室上性和室性心律失常心源性猝死糖尿病B-受體阻滯劑在冠心病中的應用從治療指南到臨床實踐（全部|類推薦）穩(wěn)定性心絞痛不穩(wěn)定性心絞痛急性心肌梗死患者心肌梗死后患者相對禁忌證患者也應積極考慮使用因為得益超過危險冠心病二級預防心力衰竭B阻滯劑開拓了心力衰竭生