Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California, USA.
Pharmacotherapy. 2021 Dec;41(12):998-1008. doi: 10.1002/phar.2633. Epub 2021 Oct 23.
Mineralocorticoid receptor antagonist (MRA) when combined with either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may provide additional benefits of cardiovascular and kidney disease risk reduction in patients with diabetic kidney disease (DKD) and hypertension. We evaluated the effectiveness of combination therapy (MRAs, either spironolactone or eplerenone, plus ACEI/ARB) compared with monotherapy (ACEI/ARB only) in patients with DKD and hypertension.
Retrospective cohort study was performed in patients (age ≥ 18 years) with hypertension, diabetes, and albuminuria between 2008 and 2018 within an integrated health system. MRA with ACEI/ARB compared to ACEI/ARB alone was evaluated on composite of cardiovascular events, progression to end-stage kidney disease, or all-cause mortality. Hyperkalemia was compared as a safety outcome.
We identified 1282 patients who received MRAs with ACEI/ARBs and 5484 patients who received ACEI/ARBs alone. Median exposure time for combination therapy was 126 days. The rates per 100 person-years of cardiovascular, kidney, or all-cause mortality outcomes were 12.2 and 9.2 for combination therapy and monotherapy, respectively (hazard ratios = 1.24, 95% Confidence Interval (CI):0.94, 1.63). Patients receiving combination therapy had greater reduction in urine albumin-to-creatinine ratio compared with monotherapy (Mean reduction: 823 and 585 mg/g; p < 0.001, respectively). Hyperkalemia was more frequent in combination therapy versus monotherapy (22.3 vs. 10.9 per 100 person-years for combination and monotherapy, respectively; hazard ratios = 1.78, 95%CI: 1.42, 2.24).
Among patients with DKD and hypertension, the short-term use of MRAs, either spironolactone or eplerenone, in combination with ACEI/ARBs, was not associated with lower risk of cardiovascular or kidney outcomes compared with ACEI/ARB monotherapy. The risk of hyperkalemia and the short duration of combination therapy may suggest a real-world clinical challenge for MRA with ACEI/ARB combination therapy.
在患有糖尿病肾病（DKD）和高血压的患者中，将醛固酮受体拮抗剂（MRA）与血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体阻滞剂（ARB）联合使用，可能会带来额外的心血管和肾脏疾病风险降低益处。我们评估了 MRA（螺内酯或依普利酮联合 ACEI/ARB）联合治疗与单药治疗（仅 ACEI/ARB）在 DKD 和高血压患者中的疗效。
在一个综合医疗系统中，对 2008 年至 2018 年间患有高血压、糖尿病和蛋白尿的年龄≥18 岁的患者进行了回顾性队列研究。将 MRA 联合 ACEI/ARB 与 ACEI/ARB 单药治疗进行比较，复合终点为心血管事件、进展为终末期肾病或全因死亡率。比较高钾血症作为安全性结果。
我们共纳入 1282 名接受 MRA 联合 ACEI/ARB 治疗的患者和 5484 名接受 ACEI/ARB 单药治疗的患者。联合治疗的中位暴露时间为 126 天。每 100 人年的心血管、肾脏或全因死亡率发生率分别为联合治疗组 12.2 例和单药治疗组 9.2 例（风险比=1.24，95%置信区间：0.94，1.63）。与单药治疗相比，接受联合治疗的患者尿白蛋白/肌酐比值降低更明显（平均降低：823 和 585mg/g；p<0.001）。与单药治疗相比，联合治疗组高钾血症更常见（分别为每 100 人年 22.3 例和 10.9 例；风险比=1.78，95%置信区间：1.42，2.24）。
在患有 DKD 和高血压的患者中，短期使用螺内酯或依普利酮联合 ACEI/ARB 的 MRA 治疗与 ACEI/ARB 单药治疗相比，并未降低心血管或肾脏结局的风险。高钾血症的风险和联合治疗的短期疗程可能表明 MRA 联合 ACEI/ARB 治疗在真实世界临床中存在挑战。
