Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease - Results from the AASK trial
Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease - Results from the AASK trial
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DOI：
10.1001/jama.288.19.2421
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发表时间：
2002-11-20
影响因子：
120.7
通讯作者：
Rostand, SG
中科院分区：
文献类型：
--
作者：
Wright, JT;Bakris, G;Rostand, SG
背景 高血压是美国终末期肾病 (ESRD) 的主要原因，目前还没有已知的治疗方法可以防止病情进行性下降导致 ESRD。 目的 比较 2 种血压 (BP) 控制水平和 3 种抗高血压药物对高血压肾小球滤过率 (GFR) 下降的影响。 设计 1995 年 2 月至 1998 年 9 月入组的随机 3 x 2 析因试验。 参与者 从美国 21 个临床中心招募了总共 1094 名 18 至 70 岁患有高血压肾病（GFR，20-65 mL/min/1.73 m(2)）的非裔美国人，并随访 3 至 6.4 年。 干预措施 参与者被随机分配到 2 个平均动脉压目标中的 1 个，即 102 至 107 mm Hg（通常；102 至 107 mm Hg）。 n=554) 或 92 毫米 Hg 或更低（较低；n=540），并使用 β 受体阻滞剂（美托洛尔 50-200 mg/d；n=441）、血管紧张素转换酶抑制剂（雷米普利 2.5-10 mg/d；n=436）或二氢吡啶钙通道阻滞剂（氨氯地平 5-10 mg/d；n=217）进行初始治疗。添加开放标签药物以实现指定的血压目标。 主要结果指标 GFR 变化率（GFR 斜率）；临床复合结果为 GFR 较基线降低 50% 或更多（或大于或等于每 1.73 m(2) 25 mL/min）、ESRD 或死亡。指定了三个主要治疗比较：与正常血压目标相比较低；雷米普利与美托洛尔；以及氨氯地平与美托洛尔。结果 低血压组的平均血压 (SD) 为 128/78 (12/8) mm Hg，正常血压组的平均血压为 141/85 (12/7) mm Hg。低血压组（每年每 1.73 m(2) -2.21 [0.17] mL/min）和普通血压组（每年每 1.73 m(2) -1.95 [0.17] mL/min；P=.24）之间，从基线到 4 年的平均 (SE) GFR 斜率没有显着差异，并且较低血压目标并未显着降低临床综合结果的发生率（降低血压的风险降低） 组=2%； 95% 置信区间 [CI]，-22% 至 21%； P=.85）。药物组比较均未显示 GFR 斜率存在一致的显着差异。然而，与美托洛尔组和氨氯地平组相比，雷米普利组的临床综合结果风险分别降低了 22% (95% CI, 1%-38%; P=.04) 和 38% (95% CI, 14%-56%; P=.004)。氨氯地平组和美托洛尔组之间的临床综合结果没有显着差异。 结论 较低的血压目标没有观察到减缓高血压肾硬化进展的额外益处。血管紧张素转换酶抑制剂似乎比 β 受体阻滞剂或二氢吡啶钙通道阻滞剂更能有效减缓 GFR 下降。
Context Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD.Objective To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension.Design Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998.Setting and Participants A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years.Interventions Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n=554) or 92 mm Hg or less (lower; n=540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n=441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n=436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n=217). Open-label agents were added to achieve the assigned BP goals.Main Outcome Measures Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or greater than or equal to25 mL/min per 1.73 m(2)) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol.Results Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m(2) per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 ml per year; P=.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group=2%; 95% confidence interval [CI], -22% to 21 %; P=.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P=.04) and 38% (95% CI, 14%-56%; P=.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups.Conclusions No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.