Background

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.

Methods

Retrospective cohort study was performed in patients (age≥18 years) with hypertension, diabetes, and albuminuria between 2008-2018 within an integrated health system. MRA with ACEI/ARB compared to ACEI/ARB alone were evaluated on composite of cardiovascular events, progression to end-stage kidney disease, or all-cause mortality. Hyperkalemia was compared as a safety outcome.

Results

We identified 1,282 patients who received MRAs with ACEI/ARBs and 5,484 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)

Conclusions

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.