Sex differences in cardiovascular-kidney-metabolic syndrome: the FINE-HEART pooled analysis

While the prevalence, drivers, and impact of cardiometabolic risk factors are known to differ between women and men, less is known about sex differences in the cardiovascular-kidney-metabolic (CKM) syndrome.

In this prespecified analysis, individual participant-level data were pooled from two trials of chronic kidney disease and type 2 diabetes (FIDELIO-DKD and FIGARO-DKD) and a trial of heart failure (HF) with mildly reduced or preserved ejection fraction (FINEARTS-HF). The risk of first HF hospitalization, cardiovascular death, major adverse cardiovascular events, kidney composite outcome, and all-cause death, was compared between men and women using adjusted Cox regression models. Treatment effect heterogeneity in response to finerenone was evaluated using interaction analyses.

Of the 18 991 participants in FINE-HEART, 6664 (35%) were women. Compared with men, women were slightly older (69 vs 67 years) and had a lower median urine albumin-to-creatinine ratio (183 vs 337 mg/g). Women were more likely to have Stage 4 CKM syndrome but less likely to receive medical therapies commonly indicated for the management of CKM conditions at baseline, such as aspirin, statins, renin-angiotensin system inhibitors, sodium-glucose co-transporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists. During a median follow-up of 2.9 years, both women and men had similarly high rates of HF hospitalization or cardiovascular death (4.8 vs 3.9 per 100 patient-years, adjusted hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.89-1.06, P = .52) but lower risk of all-cause mortality (adjusted HR 0.83, 95% CI 0.76-0.91, P < .001) compared with men. There was no evidence of treatment heterogeneity by sex with finerenone in reducing cardiovascular, kidney, and mortality outcomes (all Pinteraction >.05).

In this pooled analysis of individuals with advanced CKM syndrome, women had a higher burden of multimorbidity and were less likely to receive commonly indicated CKM therapies than men. Finerenone conferred consistent benefits in women and men, reinforcing its use while underscoring persistent sex-based treatment disparities in CKM care.

PROSPERO identifier: CRD42024570467.