Additional prognostic effect of sacubitril-valsartan and SLGT2-Inhibitors on optimal medical therapy in patients with non-ischaemic dilated cardiomyopathy

Background

Dilated cardiomyopathy (DCM) is a primary myocardial disease whose management aligns with the heart failure with reduced ejection fraction (HFrEF) therapeutic framework. Optimal medical therapy (OMT) can promote left ventricular reverse remodeling (LVRR), a key determinant of improved prognosis and reduction of major adverse cardiovascular events. However, the prognostic impact of OMT based on ARNI and/or SGLT2-I compared with ACE-I/ARB regimens in terms of survival and LVRR prevalence in DCM remains uncertain.

Aim

This study aimed to evaluate whether, and to what extent, the addition of ARNI and SGLT2-I to standard OMT influences long-term survival and promotes LVRR in patients with DCM managed according to the chronic HFrEF model.

Methods

A total of 390 patients with DCM enrolled in the Heart Muscle Disease Registry between January 2010 and June 2024 were retrospectively analyzed (mean age 53 ± 14 years; 67.9% male; baseline LVEF 31 ± 10%). Patients were divided into two treatment groups: Group 1 with OMT with ACE-I/ARB (n = 191) and Group 2 with OMT including ARNI and/or SGLT2-I (n = 199). Group 2 was further stratified according to therapy timing in Group 2A (ARNI/SGLT2-I initiated within 1 year from enrollment, n = 103) and Group 2B (ARNI/SGLT2-I initiated after >1 year from enrollment, n = 96). The following composite endpoints were analyzed: (1) overall outcomes (all-cause death, heart transplantation, or LVAD implantation); (2) cardiovascular outcomes (cardiovascular death, heart transplantation, or LVAD implantation); (3) arrhythmic outcomes (sudden cardiac death [SCD] or major ventricular arrhythmias [MVA]); (4) LVRR occurrence.

Results

During a median follow-up of 91 [57;129] months, patients in group 2 presented with a more advanced clinical profile than those in group 1 (NYHA III–IV: 36.4% vs. 24.5%, p < 0.001; LVEF 28 ± 9 vs. 34 ± 10%, p = 0.011). Despite this baseline data, Kaplan–Meier survival analysis showed similar survival rates in both groups.

Notably, early initiation of ARNI/SGLT2-I (group 2A) yielded outcomes comparable to ACE-I/ARB therapy in terms of cardiovascular and arrhythmic events.

LVRR was observed in 54% of group 1 and 56% of group 2A, whereas it occurred in only 7% of group 2B (p < 0.001). In multivariable analysis, LVRR emerged as a strong independent protective factor across all endpoints (All-cause death/HTx/LVAD: HR 0.342, 95% CI 0.193–0.608, p<0.001; Cardiovascular death/HTx/LVAD: HR 0.217, 95% CI 0.097–0.486, p<0.001; SCD/MVA: HR 0.283, 95% CI 0.148–0.540, p<0.001)

Conclusions

Survival in patients with DCM continues to improve in the contemporary era, particularly among those patients receiving early ARNI/SGLT2-I–based OMT. Early initiation of this therapy not only enhances long-term survival, but also increases the likelihood of achieving LVRR, highlighting the importance of timely pharmacological optimization in chronic HFrEF management.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.