降压治疗研究新动态回顾与展望

降压治疗研究新动态 回顾与展望 80岁以上高龄高血压 (HYVET) 高血压前期 (TROPH, PHARAO) 心房颤动 (ADVANCE post hoc) 新动态 (一 ): 扩展降压治疗获益人群 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 Days Control Ramipril Survival function PHARAO Study: Primary Endpoint Development of Hypertension Hazard ratio 0.656(0.533-0.807) Luders S, et al. J Hypertens. 2008;26:1487-1496 * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * 60 40 20 0 90 100 120 130 140 160 170 180 190 200 220 230 240 Prehypertension Uncertainty Range 55 75% of the general population % of screened population Normotension Prehypertension Masked Hypertension Sustained Hypertension Mixed population with White Coat Hypertension and Sustained Hypertension (FPs 115:2969-2975 WASID Hazard Ratios for Ischemic Stroke According to SBP and DBP No. of events/patients Median Favors Favors Hazard ratio P for Per-Ind Placebo Blood pressure Per-Ind placebo (95% CI) trend All renal events All participants 1243/5569 1500/5571 0.79 (0.73 to 0.85) Baseline systolic blood pressure (mmHg) 120 134/615 167/560 113 mmHg 0.70 (0.56 to 0.88) 0.75 120-139 367/1736 431/1793 131 mmHg 0.85 (0.74 to 0.97) 140-159 439/1945 563/2003 149 mmHg 0.75 (0.66 to 0.85) 160 303/1273 339/1215 172 mmHg 0.81 (0.70 to 0.95) Baseline diastolic blood pressure (mmHg) 70 208/846 240/881 66 mmHg 0.84 (0.70 to 1.02) 0.85 70-79 387/1748 481/1758 75 mmHg 0.77 (0.67 to 0.88) 80-89 386/1862 479/1834 84 mmHg 0.76 (0.66 to 0.87) 90 262/1113 300/1098 95 mmHg 0.81 (0.69 to 0.96) All renal events, macrovascular events, all-cause death All participants 1781/55692064/5571 0.82 (0.77 to 0.88) Baseline systolic blood pressure (mmHg) 120 190/615 205/560 113 mmHg 0.82 (0.68 to 1.00) 0.35 120-139 527/1736 590/1793 131 mmHg 0.89 (0.79 to 1.00) 140-159 615/1945 771/2003 149 mmHg 0.77 (0.69 to 0.86) 160 449/1273 498/1215 172 mmHg 0.81 (0.72 to 0.93) Baseline diastolic blood pressure (mmHg) 70 304/846 352/881 66 mmHg 0.85 (0.73 to 1.00) 0.60 70-79 551/1748 637/1758 75 mmHg 0.83 (0.74 to 0.93) 80-89 554/1852 651/1834 84 mmHg 0.81 (0.72 to 0.90) 90 372/1113 424/1098 95 mmHg 0.81 (0.71 to 0.94) 0.5 1.0 2.0 Hazard ration (95% CI) ADVANCE: Baseline BP and Outcome Events De Galan BE, et al. J Am Soc Nephrol. 2009; Feb.18, online 10 9 8 7 6 5 4 100 110 120 130 140 150 160 170 Achieved systolic blood pressure (mmHg) Annual patient event rate (%) Median systolic blood Pressure (mmHg) 106 116 125 135 144 154 168 No. of person- Years 1431 4266 8974 11983 9138 4942 3470 ADVANCE: Achieved BP levels and all renal events De Galan BE, et al. J Am Soc Nephrol. 2009; Feb.18, online 降压治疗模式的历史演进 优化联合治疗方案 纠正噻嗪类利尿剂代谢缺点 新动态 (三 ): 优化降压治疗方案 降压治疗模式的历史演进 序贯治疗 (Sequential Monotherapy) 阶梯治疗 (Stepped-care) 联合治疗 (Combination) 处方联合 单片联合 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0 Thiazide Beta blocker ACE Inhibitor Calcium channel blocker All Classes 1.04 (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 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 Monotherapy Meta-analysis from 42 trials Wald DS, et al. Am J Med. 2009;122:290-300. Diuretics ACE inhibitors or ARBs Calcium antagonists Initial Combinations of Medications for Management of Hypertension 10 8 6 4 2 0 0.5 mEq/L Decrease 0.5 mEq/L Decrease Change in Serum Potassium from Baseline Placebo Chlorthalidone Incidence Rate (per 100 person-yrs) No. of Cases 52 53 6 67 No. of Participants 1,579 1,075 179 776 SHEP Trial: Unadjusted incidence rate of diabetes in year 1 by change in serum potassium Shafi T, et al. Hypertension. 2008;52:1022-29. Thiazide Diuretics Sympathetic Nervous System Renin Angiotensin System Insulin Resistance K+ Supplement Blood FlowNa +/K+ ATPase K+p Insulinp Glucosep ? ? ? ? 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 多效性作用的单片联合治疗 (SPC) 新动态 (四 ): 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 50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。 William B, Lindholm LH, Sever P. Lancet. Published Online June 17, 2008 简化降压治疗 : STITCH研究 (Simplified Treatment Intervention to Control Hypertension) Feldman RD, et al. Hypertension. 2009;53:646-653 主要终点 (治疗 6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 (治疗 6个月时 SBP和 DBP的变化 )： STITCH 22.6/10.4 mmHg vs. CHEP 17.5/8.2 mmHg p=0.002/0.03 新动态 (五 ): 挑战