降壓治療研究新動(dòng)態(tài)回顧與展望

1、會計(jì)學(xué)1降壓治療研究新動(dòng)態(tài)回顧與展望降壓治療研究新動(dòng)態(tài)回顧與展望 80歲以上高齡高血壓歲以上高齡高血壓 (HYVET) 高血壓前期高血壓前期 (TROPH, PHARAO) 心房顫動(dòng)心房顫動(dòng) (ADVANCE post hoc)新動(dòng)態(tài)新動(dòng)態(tài)( (一一): ): 擴(kuò)展降壓治療獲益人群擴(kuò)展降壓治療獲益人群1.00.90.80.70.60.50.40.30100200300400500600700800900100011001200DaysControlRamiprilSurvival functionPHARAO Study: Primary EndpointDevelopment of Hype

2、rtensionHazard ratio0.656(0.533-0.807)Luders S, et al. J Hypertens. 2008;26:1487-1496* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *604020090100 120 130140160170180190200220230240PrehypertensionUncertainty Range 55 75% of the general

3、population% of screened populationNormotensionPrehypertensionMasked HypertensionSustainedHypertensionMixed population with WhiteCoat Hypertension and SustainedHypertension (FPs & TPs)Masked Hypertension (office BP 140/90 mmHg) (FNs)ADVANCE-AF ADVANCE-AF 研究研究 11140例例2 2型糖尿病，心房顫動(dòng)占型糖尿病，心房顫動(dòng)占7.6%。 p

4、erindopril / indapamide 降壓治療降壓治療4.3 年，年， 治療組治療組血壓比對照組降低血壓比對照組降低 5.3 / 2.3 mmHg。 心房顫動(dòng)患者降壓治療后總死亡率與心心房顫動(dòng)患者降壓治療后總死亡率與心 血管死亡率分別降低血管死亡率分別降低14%與與18%，NTT 42。Eur Heart J. 2009; March 12. online publication.The ACTIVE Steering Committee. Am Heart J. 2006; 151:1187-93Atrial fibrillation Clopidogrel Trial with

5、Irbesartan for prevention of Vascular Events 腦卒中史腦卒中史 (PROGRESS再分析再分析, WASID) 糖尿病糖尿病 (ADVANCE)新動(dòng)態(tài)新動(dòng)態(tài)(二二): 心血管高?；颊邚?qiáng)化心血管高?；颊邚?qiáng)化血壓控制血壓控制100806040200120120-139 140-159 601008060402007070-7980-89 90Achieved systolic blood pressure levels(mmHg)Achieved diastolic blood pressure levels(mmHg)Age-and sex-adjus

6、ted incidence rate CKD: P trend=0.004Non-CKD: P trend0.0001 CKD: P trend=0.001Non-CKD: P trend0.0001CKDNon-CKDIncidence rate (1000 person-years)PROGRESS - CKD Substudy: SBP and CVDWASID Trial(Warfarin-Aspirin Symtomatic Intracranial Disease)Relationship Between Blood Pressure and Strke Recurrence in

7、 Patients With Intracranial Arterial StenosisTuran TN, et al.Circulation.2007;115:2969-297510.90.80.70.60.50.40.30.20.10012345Follow-up (yrs)P0.000110.90.80.70.60.50.40.30.20.10012345Follow-up (yrs)Probability of Ischemic StrokeP0.000110.90.80.70.60.50.40.30.20.10012345Follow-up (yrs)Probability of

8、Ischemic Stroke in Territory10.90.80.70.60.50.40.30.20.10012345Follow-up (yrs)P0.0065Probability of Ischemic Stroke in TerritoryP0.0001Probability of Ischemic Stroke=160SBP=160SBPDBP=90DBP=90Turan NT, et al. Circulation. 2007;115:2969-2975WASIDHazard Ratios for Ischemic Stroke According to SBP and D

9、BP No. of events/patientsMedianFavorsFavorsHazard ratio P forPer-IndPlaceboBlood pressurePer-Indplacebo(95% CI) trendAll renal eventsAll participants1243/55691500/55710.79 (0.73 to 0.85)Baseline systolic blood pressure (mmHg)120134/615167/560113 mmHg0.70 (0.56 to 0.88)0.75120-139367/1736431/1793131

10、mmHg0.85 (0.74 to 0.97)140-159439/1945563/2003149 mmHg0.75 (0.66 to 0.85)160303/1273339/1215172 mmHg0.81 (0.70 to 0.95)Baseline diastolic blood pressure (mmHg)70208/846240/88166 mmHg0.84 (0.70 to 1.02)0.8570-79387/1748481/175875 mmHg0.77 (0.67 to 0.88)80-89386/1862479/183484 mmHg0.76 (0.66 to 0.87)9

11、0262/1113300/109895 mmHg0.81 (0.69 to 0.96)All renal events, macrovascular events, all-cause deathAll participants1781/55692064/5571 0.82 (0.77 to 0.88)Baseline systolic blood pressure (mmHg) 120190/615205/560113 mmHg0.82 (0.68 to 1.00) 0.35120-139527/1736590/1793131 mmHg0.89 (0.79 to 1.00)140-15961

12、5/1945771/2003149 mmHg0.77 (0.69 to 0.86)160449/1273498/1215172 mmHg0.81 (0.72 to 0.93)Baseline diastolic blood pressure (mmHg)70 304/846352/88166 mmHg 0.85 (0.73 to 1.00) 0.6070-79551/1748637/175875 mmHg0.83 (0.74 to 0.93)80-89554/1852651/183484 mmHg0.81 (0.72 to 0.90)90372/1113424/109895 mmHg0.81

13、(0.71 to 0.94)0.51.02.0Hazard ration (95% CI)ADVANCE: Baseline BP and Outcome EventsDe Galan BE, et al. J Am Soc Nephrol. 2009; Feb.18, online10987654100110120130140150160170Achieved systolic blood pressure (mmHg)Annual patient event rate (%)Median systolic bloodPressure (mmHg)106116125135144154168N

14、o. of person-Years14314266897411983913849423470ADVANCE: Achieved BP levels and all renal eventsDe Galan BE, et al. J Am Soc Nephrol. 2009; Feb.18, online 降壓治療模式的歷史演進(jìn)降壓治療模式的歷史演進(jìn) 優(yōu)化聯(lián)合治療方案優(yōu)化聯(lián)合治療方案 糾正噻嗪類利尿劑代謝缺點(diǎn)糾正噻嗪類利尿劑代謝缺點(diǎn)新動(dòng)態(tài)新動(dòng)態(tài)(三三): 優(yōu)化降壓治療方案優(yōu)化降壓治療方案 降壓治療模式的歷史演進(jìn)降壓治療模式的歷史演進(jìn) 序貫治療序貫治療( (Sequential Monother

15、apy) 階梯治療階梯治療( (Stepped-care) 聯(lián)合治療聯(lián)合治療( (Combination) 處方聯(lián)合處方聯(lián)合 單片聯(lián)合單片聯(lián)合1.41.21.00.80.60.40.20ThiazideBeta blockerACE InhibitorCalcium channelblockerAll Classes1.04(0.88-1.20)1.00(0.76-1.24)1.16(0.93-1.39)1.01(0.90-1.12)Adding a drug from another class(on average standard doses)Doubling dose of same

16、drug(from standard dose to twice standard)Incremental systolic blood pressure reductionRatio of observed to expected additive effects 0.89(0.69-1.09)0.19(0.08-0.30)0.23(0.12-0.34)0.2(0.14-0.28)0.37(0.29-0.45)0.22(0.19-0.25)Combination Therapy Versus MonotherapyMeta-analysis from 42 trialsWald DS, et

17、 al. Am J Med. 2009;122:290-300.Initial Combinations of Medications for Management of Hypertension1086420 0.5 mEq/L Decrease 0.5 mEq/L DecreaseChange in Serum Potassium from BaselinePlaceboChlorthalidoneIncidence Rate(per 100 person-yrs)No. of Cases5253667No. of Participants1,5791,075179776SHEP Tria

18、l: Unadjusted incidence rate of diabetes in year 1 by change in serum potassiumShafi T, et al. Hypertension. 2008;52:1022-29.Thiazide DiureticsSympatheticNervousSystemReninAngiotensinSystemInsulinResistance K+ SupplementBlood FlowNa+/K+ATPaseK+pInsulinp Glucosep? 噻嗪類利尿劑引起血糖升高的可能機(jī)制噻嗪類利尿劑引起血糖升高的可能機(jī)制Ca

19、rter BL, et al. Hypertension. 2008;52:30-36 強(qiáng)調(diào)收縮壓目標(biāo)強(qiáng)調(diào)收縮壓目標(biāo) 多效性作用的單片聯(lián)合治療多效性作用的單片聯(lián)合治療(SPC)新動(dòng)態(tài)新動(dòng)態(tài)( (四四): ): 簡化降壓治療目標(biāo)和模式簡化降壓治療目標(biāo)和模式簡化降壓治療的血壓目標(biāo)：收縮壓簡化降壓治療的血壓目標(biāo)：收縮壓 5050歲以上患者應(yīng)該以收縮壓水平為歲以上患者應(yīng)該以收縮壓水平為唯一的診斷依據(jù)和關(guān)鍵的治療目標(biāo)。唯一的診斷依據(jù)和關(guān)鍵的治療目標(biāo)。William B, Lindholm LH, Sever P. Lancet. Published Online June 17, 2008簡化降壓治療簡

20、化降壓治療: STITCH研究研究(Simplified Treatment Intervention to Control Hypertension)Feldman RD, et al. Hypertension. 2009;53:646-653主要終點(diǎn)主要終點(diǎn)( (治療治療6 6個(gè)月時(shí)血壓達(dá)標(biāo)患者比例個(gè)月時(shí)血壓達(dá)標(biāo)患者比例) )：STITCH 64.7% vs. CHEP 52.7% p=0.026 次要終點(diǎn)次要終點(diǎn)( (治療治療6 6個(gè)月時(shí)個(gè)月時(shí)SBPSBP和和DBPDBP的變化的變化) )：STITCH 22.6/10.4 mmHg vs. CHEP 17.5/8.2 mmHg p=0

21、.002/0.03新動(dòng)態(tài)新動(dòng)態(tài)(五五): 挑戰(zhàn)頑固性高血壓挑戰(zhàn)頑固性高血壓 頑固性或難治性高血壓約占整個(gè)高血壓人群頑固性或難治性高血壓約占整個(gè)高血壓人群10%-15%。除了糾正能查明的各種原因。除了糾正能查明的各種原因(繼發(fā)性、繼發(fā)性、容量或干擾因素等容量或干擾因素等)外，目前還缺乏有效的策略和外，目前還缺乏有效的策略和治療方案。治療方案。 脈沖刺激調(diào)節(jié)壓力感受器或射頻消融切斷腎交脈沖刺激調(diào)節(jié)壓力感受器或射頻消融切斷腎交感神經(jīng)感神經(jīng)(ACC 2009)，從干預(yù)病理生理環(huán)節(jié)進(jìn)行臨，從干預(yù)病理生理環(huán)節(jié)進(jìn)行臨床探索，方向是積極有益的。然而，其成功率和床探索，方向是積極有益的。然而，其成功率和長期療效

22、以及并發(fā)癥均有待進(jìn)一步深入研究。長期療效以及并發(fā)癥均有待進(jìn)一步深入研究。 降壓治療研究正在向擴(kuò)展治療人群，降壓治療研究正在向擴(kuò)展治療人群，強(qiáng)化強(qiáng)化血壓控制，血壓控制，優(yōu)化降壓治療方案，簡化優(yōu)化降壓治療方案，簡化降壓目標(biāo)和模式，挑戰(zhàn)頑固性高血壓的方降壓目標(biāo)和模式，挑戰(zhàn)頑固性高血壓的方向發(fā)展。向發(fā)展。結(jié)束語結(jié)束語The ACTIVE Steering Committee. Am Heart J. 2006; 151:1187-93Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events100806040200120120-139 140-159 601008060402007070-7980-89 90Achieved systolic blood pressure levels(mmHg)Achieved diastolic blood pressure levels(mmHg)Age-and sex-adjusted incidence rate CKD: P trend=0.004Non-CKD: P trend0.0001 CKD: P trend=0