Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy - ARTS-DN

Sep 16, 2015
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Bayer HealthCare AG
Date Published:
09/01/2015
Original Posted Date:
09/16/2015
References

Description:

The goal of the trial was to evaluate treatment with the mineralocorticoid receptor antagonist finerenone compared with placebo among subjects with diabetes and albuminuria treated with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB).

Contribution to the Literature: The ARTS-DN trial showed that finerenone reduced urinary albumin-creatinine ratio in a dose-dependent fashion.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Double-blind
  • Stratified

Diabetic subjects with albuminuria were randomized to 90 days of finerenone 1.25 mg daily (n = 96), 2.5 mg daily (n = 92), 5 mg daily (n = 100), 7.5 mg daily (n = 97), 10 mg daily (n = 98), 15 mg daily (n = 125), 25 mg daily (n = 119), or placebo (n = 94).

  • Total number of enrollees: 823
  • Duration of follow-up: 90 days
  • Mean patient age: 63 years
  • Percentage female: 27%
  • Percentage diabetics: 100%

Inclusion criteria:

  • Subjects with diabetes and albuminuria treated with an ACE inhibitor or ARB
  • Estimated glomerular filtration rate >30 cc/min/1.73 m2
  • Serum potassium ≤4.8 mmol/L

Exclusion criteria:

  • Treatment with spironolactone, eplerenone, renin inhibitor, or potassium-sparing diuretic

Principal Findings:

The primary outcome, placebo-corrected mean urinary albumin-creatinine ratio (UACR) at 90 days, was 0.79 in the 7.5 mg group (p = 0.004), 0.76 in the 10 mg group (p = 0.01), 0.67 in the 15 mg group (p < 0.001), and 0.62 in the 20 mg group (p < 0.001).

Secondary outcome: Hyperkalemia leading to study drug discontinuation was 2.1% in the 7.5 mg group, 0% in the 10 mg group, 3.2% in the 15 mg group, 1.7% in the 20 mg group, and 1.5% for placebo.

Interpretation:

Among diabetic individuals with albuminuria treated with an ACE inhibitor or ARB, finerenone resulted in a dose-dependent decrease in mean UACR. This was significant for the 7.5 mg, 10 mg, 15 mg, and 20 mg doses. Finerenone was well-tolerated with a low frequency of hyperkalemia, resulting in study drug discontinuation. While these results appear promising, UACR is a surrogate outcome; therefore, studies powered for clinical outcomes are warranted.

References:

Bakris GL, Agarwal R, Chan JC, et al., on behalf of the Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy (ARTS-DN) Study Group. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA 2015;314:884-94.

Keywords: Albuminuria, Angiotensin-Converting Enzyme Inhibitors, Diabetes Mellitus, Diabetic Nephropathies, Hyperkalemia, Metabolic Syndrome, Mineralocorticoid Receptor Antagonists, Primary Prevention


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