Nakayamadera Imai Clinic, Takarazuka, Japan.
Hypertens Res. 2013 Dec;36(12):1051-9. doi: 10.1038/hr.2013.86. Epub 2013 Sep 12.
Combination therapy with angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors (ACEIs) requires further evaluation in patients with diabetic nephropathy and hypertension. In a post hoc analysis of the Olmesartan Reducing Incidence of Endstage renal disease in diabetic Nephropathy Trial with hypertension, we examined the effects of olmesartan on renal and cardiovascular outcomes in the presence or absence of an ACEI. Among 563 patients randomized to receive either olmesartan (n = 280) or placebo (n = 283), 73.5% (n = 414) received a concomitant ACEI. Compared with placebo, olmesartan significantly reduced proteinuria in both the ACEI-treated and non-ACEI-treated groups. The respective changes in the urinary protein creatinine ratio in the olmesartan-treated and placebo-treated groups were -32.6% and +21.1% without an ACEI (P = 0.001) and -17.0% and +2.2% with an ACEI (P = 0.028). In the olmesartan group, 115 patients developed primary renal outcomes (41.1%) compared with 129 (45.6%) in the placebo group (hazard ratio (HR): 0.97, P = 0.787). The respective HRs in the ACEI-treated and non-ACEI-treated groups were 1.02 (P = 0.891) and 0.84 (P = 0.450). 40 olmesartan-treated patients (14.3%) and 53 placebo-treated patients (18.7%) developed secondary cardiovascular outcomes (HR: 0.65, P = 0.042). The respective HRs in the ACEI-treated and non-ACEI-treated groups were 0.69 (P = 0.129) and 0.51 (P = 0.129). Olmesartan was well tolerated. Dual blockade treatment caused more hyperkalemia than monotherapy. In patients with diabetic nephropathy and hypertension, olmesartan significantly reduced proteinuria, independent of ACEI treatment and cardiovascular outcome but failed to show additional renal benefit compared with ACEI treatment alone. The cardiovascular benefit of dual treatment requires further evaluation.
血管紧张素 II 受体阻滞剂和血管紧张素转换酶抑制剂 (ACEI) 的联合治疗在糖尿病肾病和高血压患者中需要进一步评估。在 Olmesartan 降低糖尿病肾病高血压终点事件发生率试验的事后分析中，我们研究了奥美沙坦在存在或不存在 ACEI 的情况下对肾脏和心血管结局的影响。在随机接受奥美沙坦（n=280）或安慰剂（n=283）的 563 名患者中，73.5%（n=414）接受了 ACEI 联合治疗。与安慰剂相比，奥美沙坦在 ACEI 治疗组和非 ACEI 治疗组均显著降低蛋白尿。奥美沙坦治疗组和安慰剂治疗组的尿蛋白/肌酐比值变化分别为 -32.6%和+21.1%（无 ACEI 时，P=0.001）和 -17.0%和+2.2%（有 ACEI 时，P=0.028）。奥美沙坦组有 115 例患者发生主要肾脏结局（41.1%），安慰剂组有 129 例（45.6%）（风险比（HR）：0.97，P=0.787）。ACEI 治疗组和非 ACEI 治疗组的 HR 分别为 1.02（P=0.891）和 0.84（P=0.450）。40 名奥美沙坦治疗患者（14.3%）和 53 名安慰剂治疗患者（18.7%）发生次要心血管结局（HR：0.65，P=0.042）。ACEI 治疗组和非 ACEI 治疗组的 HR 分别为 0.69（P=0.129）和 0.51（P=0.129）。奥美沙坦耐受性良好。双重阻断治疗引起的高钾血症多于单药治疗。在糖尿病肾病和高血压患者中，奥美沙坦可显著降低蛋白尿，独立于 ACEI 治疗和心血管结局，但与 ACEI 单药治疗相比，未能显示出额外的肾脏获益。双重治疗的心血管获益需要进一步评估。
