降压治疗研究新动态回顾与展望

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1、降压治疗研究新动态降压治疗研究新动态 回顾与展望回顾与展望 80岁以上高龄高血压岁以上高龄高血压(HYVET)高血压前期高血压前期(TROPH,PHARAO)心房颤动心房颤动(ADVANCE post hoc)新动态新动态(一一):):扩展降压治疗获益人群扩展降压治疗获益人群1.00.90.80.70.60.50.40.30100200300400500600700800900100011001200DaysControlRamiprilSurvival functionPHARAO Study:Primary EndpointDevelopment of HypertensionHazard

2、 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 population%of screened populationNormotensionPrehypertensionMasked HypertensionSustainedHypertensionMixed population with WhiteCoa

3、t 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，心房颤动占型糖尿病，心房颤动占7.6%。perindopril/indapamide 降压治疗降压治疗4.3 年，年，治疗组治疗组血压比对照组降低血压比对照组降低 5.3/2.3 mmHg。心房颤动患者降压治疗后总死亡率与心心房颤动患者降压治疗后总死亡率与心 血管死亡率分别降低血管死亡率分别降低14%与与18%，NTT 4

4、2。Eur Heart J.2009;March 12.online publication.The ACTIVE Steering Committee.Am Heart J.2006;151:1187-93Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events 脑卒中史脑卒中史(PROGRESS再分析再分析,WASID)糖尿病糖尿病(ADVANCE)新动态新动态(二二):心血管高危患者强化心血管高危患者强化血压控制血压控制100806040200120120-139 140

5、-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=0.001Non-CKD:P trend0.0001CKDNon-CKDIncidence rate(1000 person-years)PROGRESS-CKD Substu

6、dy:SBP and CVDWASID Trial(Warfarin-Aspirin Symtomatic Intracranial Disease)Relationship Between Blood Pressure and Strke Recurrence in 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

7、.30.20.10012345Follow-up(yrs)Probability of Ischemic StrokeP0.000110.90.80.70.60.50.40.30.20.10012345Follow-up(yrs)Probability of 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=160SB

8、P=160SBPDBP=90DBP=90Turan NT,et al.Circulation.2007;115:2969-2975WASIDHazard Ratios for Ischemic Stroke According to SBP and DBP No.of events/patientsMedianFavorsFavorsHazard ratio P forPer-IndPlaceboBlood pressurePer-Indplacebo(95%CI)trendAll renal eventsAll participants1243/5569 1500/55710.79(0.73

9、 to 0.85)Baseline systolic blood pressure(mmHg)120134/615167/560113 mmHg0.70(0.56 to 0.88)0.75120-139367/1736431/1793131 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

10、.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)90262/1113300/109895 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)

11、120190/615205/560113 mmHg0.82(0.68 to 1.00)0.35120-139527/1736590/1793131 mmHg0.89(0.79 to 1.00)140-159615/1945771/2003149 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

12、mmHg0.83(0.74 to 0.93)80-89554/1852651/183484 mmHg0.81(0.72 to 0.90)90372/1113424/109895 mmHg0.81(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

13、)Annual patient event rate(%)Median systolic bloodPressure(mmHg)106116125135144154168No.of person-Years14314266897411983913849423470ADVANCE:Achieved BP levels and all renal eventsDe Galan BE,et al.J Am Soc Nephrol.2009;Feb.18,online 降压治疗模式的历史演进降压治疗模式的历史演进 优化联合治疗方案优化联合治疗方案 纠正噻嗪类利尿剂代谢缺点纠正噻嗪类利尿剂代谢缺点新动态

14、新动态(三三):优化降压治疗方案优化降压治疗方案 降压治疗模式的历史演进降压治疗模式的历史演进 序贯治疗序贯治疗(Sequential Monotherapy)阶梯治疗阶梯治疗(Stepped-care)联合治疗联合治疗(Combination)处方联合处方联合 单片联合单片联合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 dru

15、g from another class(on average standard doses)Doubling dose of same 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)Combinat

16、ion Therapy Versus MonotherapyMeta-analysis from 42 trialsWald DS,et 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-y

17、rs)No.of Cases5253667No.of Participants1,5791,075179776SHEP Trial: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+ATPas

18、eK+pInsulinp Glucosep?噻嗪类利尿剂引起血糖升高的可能机制噻嗪类利尿剂引起血糖升高的可能机制Carter BL,et al.Hypertension.2008;52:30-36 强调收缩压目标强调收缩压目标 多效性作用的单片联合治疗多效性作用的单片联合治疗(SPC)新动态新动态(四四):):简化降压治疗目标和模式简化降压治疗目标和模式简化降压治疗的血压目标：收缩压简化降压治疗的血压目标：收缩压 5050岁以上患者应该以收缩压水平为岁以上患者应该以收缩压水平为唯一的诊断依据和关键的治疗目标。唯一的诊断依据和关键的治疗目标。William B,Lindholm LH,Sever

19、 P.Lancet.Published Online June 17,2008简化降压治疗简化降压治疗:STITCH研究研究(Simplified Treatment Intervention to Control Hypertension)Feldman RD,et al.Hypertension.2009;53:646-653主要终点主要终点(治疗治疗6 6个月时血压达标患者比例个月时血压达标患者比例)：STITCH 64.7%vs.CHEP 52.7%p=0.026 次要终点次要终点(治疗治疗6 6个月时个月时SBPSBP和和DBPDBP的变化的变化)：STITCH 22.6/10.4

20、mmHg vs.CHEP 17.5/8.2 mmHg p=0.002/0.03新动态新动态(五五):挑战顽固性高血压挑战顽固性高血压 顽固性或难治性高血压约占整个高血压人群顽固性或难治性高血压约占整个高血压人群10%-15%。除了纠正能查明的各种原因。除了纠正能查明的各种原因(继发性、继发性、容量或干扰因素等容量或干扰因素等)外，目前还缺乏有效的策略和外，目前还缺乏有效的策略和治疗方案。治疗方案。脉冲刺激调节压力感受器或射频消融切断肾交脉冲刺激调节压力感受器或射频消融切断肾交感神经感神经(ACC 2009)，从干预病理生理环节进行临，从干预病理生理环节进行临床探索，方向是积极有益的。然而，其成功率和床探索，方向是积极有益的。然而，其成功率和长期疗效以及并发症均有待进一步深入研究。长期疗效以及并发症均有待进一步深入研究。降压治疗研究正在向扩展治疗人群，降压治疗研究正在向扩展治疗人群，强化强化血压控制，血压控制，优化降压治疗方案，简化优化降压治疗方案，简化降压目标和模式，挑战顽固性高血压的方降压目标和模式，挑战顽固性高血压的方向发展。向发展。结束语结束语