Sex differences in adherence to guideline-directed medical therapy and their prognostic impact in HFrEF: insights from the KorAHF III registry

Background

Guideline-directed medical therapy (GDMT) is essential for reducing morbidity and mortality in HFrEF. However, real-world optimization remains suboptimal. Women are particularly less likely to receive optimized GDMT, often due to smaller body size, physiological differences, and increased susceptibility to adverse reactions. Despite these known gaps, sex-specific data on the prognostic impact of GDMT adherence are limited, therefore, we aimed to investigate sex differences in GDMT adherence and its association with clinical outcomes in patients with HFrEF.

Methods

This study analyzed data from the KorAHF III registry, a nationwide, prospective, multicenter cohort enrolling patients hospitalized with acute heart failure in Korea. We included patients with HFrEF and assessed outcomes over a 12-month follow-up period. Physician adherence to guideline-recommended treatment was quantified using a standardized score based on the prescription and target dosing of key heart failure medications. The primary outcome was a composite of cardiovascular death and heart failure hospitalization.

Results

Among a total of 4,153 patients, prescription rates for RAS inhibitors (59.7% vs. 55.3%, P < 0.001), MRAs (39.9% vs. 36.0%, P = 0.039), and SGLT2 inhibitors (20.1% vs. 15.2%, P < 0.001) were significantly higher in men, whereas no significant sex-based difference was observed for beta-blockers (55.4% vs. 54.3%, P = 0.818).

In whole study population, 2,925 (70.4%) were classified into the poor adherence group, 1,133 (27.3%) into the moderate adherence group, and 95 (2.3%) into the good adherence group. The mean adherence score was significantly higher in men than in women (0.31±0.26 vs. 0.26± 0.24, P < 0.001). The proportion of patients in the poor adherence group was higher in women than men (76.1% vs. 67.4%), while the proportion of patients with good adherence was higher in men (2.6% vs. 1.7%, P<0.001).

Kaplan-Meier analysis demonstrated that the poor adherence group had the worst prognosis regardless of sex (figure). Specifically, the poor adherence group showed a significantly higher risk of mortality and heart failure rehospitalization compared to the good (P < 0.001) and moderate (P = 0.036) adherence groups. However, there were no significant sex-specific differences in survival outcomes within the same adherence levels (Poor: P = 0.322; Moderate: P = 0.845; Good: P = 0.555).

Conclusion

In this nationwide cohort of patients with HFrEF, women were less likely to receive GDMT than men. Higher adherence to GDMT was associated with better clinical outcomes in both sexes, underscoring the importance of improving GDMT implementation in routine practice. Notably, in this Asian population, moderate adherence was not associated with substantially worse outcomes compared with good adherence, suggesting that optimal dosing strategies may need to be tailored to patient characteristics, including sex and ethnicity.For image description, please refer to the figure legend and surrounding text.