Cardiology ยท Medical Literature
Racial outcomes in patients with diabetic cardiomyopathy treated with an aldose reductase inhibitor: the ARISE-HF trial.
Abstract
Racial and ethnic differences in diabetic cardiomyopathy (DbCM) exist, with black and Hispanic participants showing poorer health status. It remains unclear whether these differences affect the natural progression of the disease. We aimed to evaluate disease progression in individuals with DbCM, as well as racial differences in the response to AT-001. A total of 625 participants with DbCM were randomised to either placebo or AT-001 and followed for 15 months. The primary outcome was change in peak oxygen uptake (peak VO2) and secondary outcomes included Kansas City Cardiomyopathy Questionnaire (KCCQ) and Physical Activity Scale for the Elderly scores. Analyses were stratified by race and ethnicity (black, Hispanic, white). Black and Hispanic participants who received placebo experienced greater declines in peak VO2 (-0.74 and -1.67 mL/kg/min, respectively) compared with white participants (-0.23 mL/kg/min, p=0.005). AT-001 demonstrated a non-statistically significant trend towards slower declines in peak VO2 in black and Hispanic participants (-0.31 and -0.62 mL/kg/min, p=0.29, respectively). Black participants who received placebo had the largest declines in most KCCQ scores. Black and Hispanic participants with DbCM experienced faster disease progression, with black participants showing the most pronounced functional and quality of life declines. The effect of AT-001 on peak VO2 changes was not statistically significant with similar effects between racial and ethnic groups (NCT04083339). NCT04083339.
Clinical relevance
Diabetic cardiomyopathy (DbCM) disproportionately affects racial and ethnic minorities, yet prospective data on differential disease progression across racial groups have been limited. The ARISE-HF trial provides the first randomized, controlled evidence quantifying racial disparities in functional decline among patients with DbCM, directly informing risk stratification in a high-burden population. Clinicians managing Black and Hispanic patients with DbCM should recognize that these groups face accelerated cardiopulmonary and quality-of-life deterioration, warranting heightened surveillance and earlier therapeutic consideration.
Key findings
1. Black participants receiving placebo experienced a mean decline in peak VO2 of -0.74 mL/kg/min over 15 months, and Hispanic participants -1.67 mL/kg/min, compared with -0.23 mL/kg/min in white participants (p=0.005), confirming statistically significant racial differences in rate of functional decline. 2. AT-001 (an aldose reductase inhibitor) attenuated peak VO2 decline in Black participants to -0.31 mL/kg/min and in Hispanic participants to -0.62 mL/kg/min; however, these improvements did not reach statistical significance (p=0.29). 3. The effect of AT-001 on peak VO2 was not statistically significant overall, and no statistically significant differential treatment effect by racial or ethnic subgroup was demonstrated. 4. Black participants assigned to placebo exhibited the largest declines across most Kansas City Cardiomyopathy Questionnaire (KCCQ) domain scores, indicating disproportionate health-status deterioration beyond aerobic capacity alone. 5. The trial enrolled 625 participants randomized to AT-001 or placebo with 15-month follow-up, using peak VO2 as the primary endpoint and KCCQ and Physical Activity Scale for the Elderly (PASE) as secondary endpoints. 6. Despite a non-significant trend toward benefit with AT-001 in minority subgroups, the study was likely underpowered for race-stratified subgroup analyses, limiting definitive conclusions about differential therapeutic efficacy.
Practice implications
Clinicians should recognize Black and Hispanic patients with DbCM as a high-risk phenotype for accelerated cardiopulmonary and functional decline, and consider more frequent reassessment of exercise capacity (e.g., cardiopulmonary exercise testing) and health-status metrics (e.g., KCCQ) in these populations to facilitate timely escalation of guideline-directed therapy. Although AT-001 showed a non-significant trend toward attenuating peak VO2 decline in minority patients, it cannot currently be recommended for this indication outside of a clinical trial given the absence of statistical significance. Future trials evaluating novel disease-modifying therapies for DbCM should be adequately powered for race- and ethnicity-stratified analyses to determine whether observed biological trends translate into meaningful differential treatment effects.