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1、降压治疗研究新动向降压治疗研究新动向强化、优化和简化强化、优化和简化 扩展降压治疗能获益的人群扩展降压治疗能获益的人群，当前，当前主要聚焦主要聚焦在在80岁以上高龄高血压患者和岁以上高龄高血压患者和血压水平血压水平140/90的心血管高危患者的心血管高危患者(心、心、脑血管病与糖尿病脑血管病与糖尿病)。新动向新动向( (一一) )The results of this trial should provide reliable evidence about the effects of blood-pressure-lowering therapy in this very high-risk
2、 population.安慰剂安慰剂纳催离缓释片 雅施达安慰剂HYVET: 总死亡率总死亡率总死亡率降低总死亡率降低21%随访时间（年）百分率% 纳催离缓释片纳催离缓释片雅施达雅施达1912193314921565814877379420202231从从HYVET到临床实践到临床实践 适用于收缩压适用于收缩压160mmHg以上，一般状况以上，一般状况尚好，生活能自理，认知功能无明显减退的高尚好，生活能自理，认知功能无明显减退的高龄高血压患者。龄高血压患者。 降压速度应该相对较平缓，避免体位性低降压速度应该相对较平缓，避免体位性低血压。血压控制目标值血压。血压控制目标值150/80mmHg。 R
3、ASRAS阻滞剂治疗心血管高危患者阻滞剂治疗心血管高危患者循证证据循证证据HOPE (Ramipril,2000)PROGRESS (Perindopril, 2001)EUROPA (Perindopril, 2003)ADVANCE (Perin/Indap, 2007)ONTARGET (Telmisartan, 2008)HOPE 139/79 3/3PROGRESS 147/86 9/4EUROPA 137/82 5/2ADVANCE 145/81 5/3ONTARGET 142/82 6/4 基线血压基线血压 血压血压RAS阻滞剂治疗心血管高危患者阻滞剂治疗心血管高危患者基线血压与
4、血压下降幅度基线血压与血压下降幅度mmHgmmHgHTHTNTNTS SD D159.0159.0159.0159.094.094.091.091.0136.0136.0127.2127.279.079.074.874.8Blood Pressure values in PROGRESS 在心血管高危患者在心血管高危患者, 强化强化血压控制。血压控制。血压控制目标值血压控制目标值130/80mmHg正在不断正在不断获得循证证据获得循证证据。新动向新动向( (二二) )SBPFrom UKPDS to ADVANCEUKPDSADVACCORD StudyAction to Control Ca
5、rdiovascular risk in DiabetesPrisant LM. J Clin Pharmacol 2004; 44(4):423-430 HbA1c: 6.0% vs 7.0-7.9% (因因强强化治化治疗总疗总死亡率增加死亡率增加, ,0808年年2 2月月7 7日日宣布提前中止宣布提前中止) ) SBP: 120 mmHg vs 140 mmHg 100120140160180Systolic blood pressure (mmHg)1248Annual rate (%)Ischaemic stroke100120140160180Systolic blood pres
6、sure (mmHg)0.010.020.040.080.160.32Haemorrhagic strokeArima H, et al. J Hypertens. 2006;24:1201-1208PROGRESS: Adjusted relative of doubling of serum creatinine or ESRD (95% CI)Usual systolic BP (mm Hg) during follow-upProteinuria 1g/dayProteinuria 1g/day106121604.805.408.401.701.20.702.224.811.60Ref
7、erence1.2100806040200120120-139 140-159 601008060402007070-7980-89 90Achieved systolic blood pressure levels(mmHg)Achieved systolic 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
8、 (1000 person-years)PROGRESS CKD Substudy: SBP and CVD020406080100110100120 130 140 150 160 170 180 190 200 210 220Nadir, 129.5 mm HgSystolic Blood pressure, mm hgRelative Hazard, 3700204060801005060708090100110120Nadir, 73.8 mm HgDiastolic Blood pressure, mm hgRelative Hazard, 2200Messerli FH, et a
9、l. Ann Intern Med. 2006;144:884-893 冠心病患者血压控制水平与心血管危险冠心病患者血压控制水平与心血管危险Rosendorff C, et al. Circulation 2007;115:Treatment of Hypertension in IHDA Scientific Statement from AHA, 2007.4 冠心病患者需要积极控制血压，合理的血压控冠心病患者需要积极控制血压，合理的血压控 制目标值制目标值130/80mmHg。（。（a,B） 应该相对缓慢降低血压，避免应该相对缓慢降低血压，避免DBP60mmHg。 优化降压治疗方案优化降
10、压治疗方案，比较不同降压，比较不同降压治疗药物和治疗方案在长期治疗过程中治疗药物和治疗方案在长期治疗过程中对血压控制、靶器官、不良反应、代谢对血压控制、靶器官、不良反应、代谢以及终点事件等影响的差异以及终点事件等影响的差异。 新动向新动向( (三三) )0-2-4-6-8-10-12-14-16-180-2-4-6-8-10-12-14PlaceboPlaceboLosartanLosartanValsartanValsartanIrbesartanIrbesartanCandesartenCandesartenTelmisartanEprosatanEprosatanTelmisartanO
11、lmesartanOlmesartanSystolic BPSystolic BPDiastolic BPDiastolic BPARBARB动态血压监测研究系统综述动态血压监测研究系统综述24h24h平均下降值平均下降值Fabia MJ, et al. J Hypertens. 2007;25:1327-13360-2-4-6-8-10-12-14-16-180-2-4-6-8-10-12-14PlaceboPlaceboLosartanLosartanValsartanValsartanIrbesartanIrbesartanCandesartenCandesartenTelmisarta
12、nEprosatanEprosatanTelmisartanOlmesartanOlmesartanSystolic BPSystolic BPDiastolic BPDiastolic BPARBARB动态血压监测研究系统综述动态血压监测研究系统综述治疗后治疗后18-24h18-24h平均下降值平均下降值Fabia MJ, et al. J Hypertens. 2007;25:1327-13361001009090808070706060505040403030202010100 0Patients (%)Patients (%)Treatment GroupsTreatment Grou
13、psN N11561156= =7817819696907907355355646646335335320/CTZ320/CTZ320320160/HCTZ160/HCTZ160160808080/12.580/12.5PlaceboPlacebo7.07.013.113.124.224.24.84.816.716.732.632.63.13.133.333.351.451.417.917.932.832.848.448.425.825.856.456.474.674.622.522.535.735.754.254.245.245.267.167.184.884.82 wk2 wk4 wk4
14、wk8 wk8 wkWeir MR, et al. Am J Hypertens 2007;20:807 缬沙坦剂量对降压疗效的影响缬沙坦剂量对降压疗效的影响达标率和达标时间达标率和达标时间6060707080809090100100505040403030202010100 00 07 71414212128283535424249495656Duration of Treatment (days)Duration of Treatment (days)Patients Achieving Goal (%)Patients Achieving Goal (%)ValsartanValsart
15、an 320/HCTZ 320/HCTZValsartanValsartan 160/HCTZ 160/HCTZValsartanValsartan 320 320ValsartanValsartan/HCTZ 80/125/HCTZ 80/125ValsartanValsartan 160 160ValsartanValsartan 80 80PlaceboPlaceboWeir MR, et al. Am J Hypertens 2007;20:807缬沙坦不同剂量对降压疗效的影响缬沙坦不同剂量对降压疗效的影响Reduction of proteinuria after one year
16、of treatment:29% with Micardis 80 vs. 20% with losartan 100, p0.05Comparative Long term Efficacy of Two AT1 Receptor Blockers (Telmisartan vs. Losartan) on Proteinuria in Patients with Type-2 Diabetes and Overt Nephropathy and HypertensionBakris G, et al. 22th ASH Meeting, May 21, 2007, CHICAGOJ hyp
17、ertens. 2005; 23: 445-453.NICE Combi Study(Nifedipine and Candesartan Combination)Controlled-release nifedipine and candesartan low-dose combination therapy in patients with essential hypertensionCombinationUptitrationNICE Combi Study Nifedipine CR & Candesartan versus High Dose Candesartan00.02-0.0
18、2-0.04-0.06-0.08-0.10-0.12两组间P 0.002JMICB:长效硝苯地平与长效硝苯地平与ACEI延缓冠状动脉粥硬化进展的比较延缓冠状动脉粥硬化进展的比较长效硝苯地平ACEI治疗持续3年治疗后冠脉管腔最小直径变化（mm）0.020.27 mmP 0.5430.120.27 mmP 0.001Shinoda E, et al. Hypertension. 2005 Jun;45(6):1153-8.Ram(n=8576)%Ram + Tel (n=8502)%Ram + Tel v Ram RR (95% CI)P valueAny renal dysfunction*10
19、.0413.351.33 (1.22-1.45)5.5 mmol/L3.325.671.71 (1.48-1.98)0.0001SAE renal failure0.280.642.27 (1.40-3.67)0.0006Need for dialysis0.550.781.42 (0.98-2.06)0.066Death after renal dysfunction1.842.211.20 (0.97-1.48)0.087*local definitionONTARGET:Renal Dysfunction Dialysis & Related DeathTel + Ram vs. Ram
20、 在心血管高危患者，常同时存在以肾小动脉在心血管高危患者，常同时存在以肾小动脉硬化和缺血性损害为特点的硬化和缺血性损害为特点的CKDCKD。糖尿病性和非糖尿病性和非糖尿病性肾病糖尿病性肾病与与慢性缺血性肾脏病慢性缺血性肾脏病在病理生理、在病理生理、诊断和治疗方面应当有所切割。诊断和治疗方面应当有所切割。Antihypertensive drug treatment and the development of diabetes：Meta-analysisARBsARBs多效性的差异多效性的差异 Uric acid excretionPPAR gammaSNS inhibitonAnti-inf
21、l/AntiplateletAT1-blockadeAT2-stimulationTelmisartan, EXP 3179 EprosartanEXP 3179 Class-EffectBalance varies Magnitude variesDepending on doseLosartan降压药物多效性降压药物多效性(pleiotropic)的临床意义的临床意义 降压药物多效性的协同作用有利于降压治疗中降压药物多效性的协同作用有利于降压治疗中多种心血管危险因素的综合控制，有助于保护靶器多种心血管危险因素的综合控制，有助于保护靶器官和干预病理生理环节，从而在特定情况下可能转官和干预病理
22、生理环节，从而在特定情况下可能转化为更大程度地降低心血管危险。化为更大程度地降低心血管危险。 降压药物多效性将成为临床优化选择降压药物的降压药物多效性将成为临床优化选择降压药物的重要依据和靓点。重要依据和靓点。（氨氯地平（氨氯地平+/-培哚普利培哚普利 Vs. 阿替洛尔阿替洛尔+/-苄氟噻嗪）苄氟噻嗪）*P0.05降低百分比(%)-35-30-25-20-15-10-50*非致死心梗和冠心病死亡心血管死亡总死亡总冠脉事件致死/非致死性卒中总心血管事件和介入新发糖尿病肾损害Dahlof B, Sever P, et al. Lancet. 2005;366:895-906. ASCOT-BPLA
23、:ASCOT-BPLA:终点事件发生率终点事件发生率累计事件发生率（%）HR (95% CI): 0.80 (0.72, 0.90)(天)P = 0.0002ACEI / HCTZCCB / ACEI650526Kenneth Jamerson, et al. Late Breaker presentation at ACC 2008. ACCOMPLISH: 心血管复合终点心血管复合终点20%ACCOMPLISH: 意义意义 对特定人群选择优化的对特定人群选择优化的降压治疗方案降压治疗方案提供了提供了循证证据。循证证据。 ACEI / CCB联合特别有利于减少冠心病事件联合特别有利于减少冠心
24、病事件(心肌梗死、不稳定性心绞痛、血运重建心肌梗死、不稳定性心绞痛、血运重建)。 在优化的基础上，在优化的基础上，简化降压治疗模简化降压治疗模式式, ,寻找强效、快捷、平稳和安全的联寻找强效、快捷、平稳和安全的联合治疗方案和途径。合治疗方案和途径。新动向新动向( (三三) ) 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)Choose betweenLow-dose 2-drug combinationLow-dose singl
25、e agentNot at BP goalFull dose ofsingle agentSwitch todifferent agentat low doseFull dose of2-drugcombinationAdd athird drugat low doseNot at BP goal23 drugcombinationat full doseFull doses of 23-drugcombinationFull-dosesingle agentMarked BP elevationHigh/very high CV riskLower BP targetMild BP elev
26、ationLow/moderate CV riskConventional BP targetTask Force for ESHESC. J Hypertens 2007;25:110587Algorithm for Treatment of Hypertension(ESH/ESC) TALENT study STudy EvALuating the Efficacy of Nifedipine GITS -Telmisartan in Blood Pressure Controli) Nifedipine GITS 20 mg then add Telmisartan ii) Telmi
27、sartan then add Nifedipine iii) Nifedipine / Telmisartan combinationPercentage of patients fully adherent to fixed-doseCombination therapy and coadministered 2-pill therapy10090807060504030201000369121518212427Months after start of therapy21%17%Percentage of patients fully adherentFixed-dose combinationCoadministration of 2 pillsSturkenboom M, et al. 15th ESH meeting, Milan, Italy, June 17-21, 2005
