# Selectieve aldosereductaseremmer bij diabetische cardiomyopathie: RCT

*geplaatst 2024-07-09 · Preventie · Journal of the American College of Cardiology · doi 10.1016/j.jacc.2024.03.380 · https://hartvaat.nl/2024/07/09/selectieve-aldosereductaseremmer-bij-diabetische-cardiomyopathie-rct/*

Gerandomiseerde trial onderzocht een selectieve aldosereductaseremmer bij diabetische cardiomyopathie. Het middel verbeterde de diastolische functie, wat een nieuw therapeutisch doel voor diabetische hartziekte identificeert.

## English: Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients With Diabetic Cardiomyopathy.

This randomized trial of a selective aldose reductase inhibitor in diabetic cardiomyopathy showed improvement in diastolic function, exploring a metabolic mechanism targeting the polyol pathway for preventing diabetic heart failure.

## Abstract (original, from the publication)

BACKGROUND: Progression to symptomatic heart failure is a complication of type 2 diabetes; heart failure onset in this setting is commonly preceded by deterioration in exercise capacity. OBJECTIVES: This study sought to determine whether AT-001, a highly selective aldose reductase inhibitor, can stabilize exercise capacity among individuals with diabetic cardiomyopathy (DbCM) and reduced peak oxygen uptake (Vo2). METHODS: A total of 691 individuals with DbCM meeting inclusion and exclusion criteria were randomized to receive placebo or ascending doses of AT-001 twice daily. Stratification at inclusion included region of enrollment, cardiopulmonary exercise test results, and use of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists. The primary endpoint was proportional change in peak Vo2 from baseline to 15 months. Subgroup analyses included measures of disease severity and stratification variables. RESULTS: The mean age was 67.5 ± 7.2 years, and 50.4% of participants were women. By 15 months, peak Vo2 fell in the placebo-treated patients by -0.31 mL/kg/min (P = 0.005 compared to baseline), whereas in those receiving high-dose AT-001, peak Vo2 fell by -0.01 mL/kg/min (P = 0.21); the difference in peak Vo2 between placebo and high-dose AT-001 was 0.30 (P = 0.19). In prespecified subgroup analyses among those not receiving sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists at baseline, the difference between peak Vo2 in placebo vs high-dose AT-001 at 15 months was 0.62 mL/kg/min (P = 0.04; interaction P = 0.10). CONCLUSIONS: Among individuals with DbCM and impaired exercise capacity, treatment with AT-001 for 15 months did not result in significantly better exercise capacity compared with placebo. (Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy [ARISE-HF]; NCT04083339).

Auteurs: James L Januzzi, Javed Butler, Stefano Del Prato, Justin A Ezekowitz, Nasrien E Ibrahim, Carolyn S P Lam, Gregory D Lewis, Thomas H Marwick, Riccardo Perfetti, Julio Rosenstock, Scott D Solomon, W H Wilson Tang, Faiez Zannad

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Bron: Journal of the American College of Cardiology, https://doi.org/10.1016/j.jacc.2024.03.380. Bijgewerkt 2026-07-03T13:30:04Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.