Early achievement of optimal medical therapy and its impact on survival and morbidity: results from a nationwide implementation science study (BRING-UP-3 HF)
C Basile, F Orso, F Oliva, M G Cipriani, F Colivicchi, A Di Lenarda, M Gori, M Gorini, M Iacoviello, M Marini, D Gabrielli, A P MaggioniAbstract
Background
The suboptimal use of guideline-directed medical therapy (GDMT) is a key factor in the ongoing challenges of implementing effective heart failure (HF) management strategies. Recent evidence suggests that the speed of reaching optimal medical therapy (OMT), defined as all GDMT, is key in reducing morbidity and mortality in HF. However, evidence on the feasibility of rapid optimization and its prognostic impact in real-world settings is lacking.
Purpose
To identify predictors of OMT achievement and evaluate the association between time to OMT implementation and a primary composite outcome of 12-month total HF hospitalization, emergency department visits, and cardiovascular mortality, as well as the secondary outcome of all-cause mortality.
Methods
We utilized data from 5,203 ambulatory and hospitalized patients with HF enrolled in the BRING-UP-3 HF multicenter, observational study. Ejection fraction (EF) categories were defined according to the Universal Definition of HF. OMT was defined as the ‘’four-pillar’’ therapy and for HF with reduced or improved EF (HFrEF/HFimpEF) and sodium glucose co-transporter type 2 inhibitors (SGLT2i) use for HF with mildly reduced or preserved EF (HFmrEF/HFpEF). We employed multivariable-adjusted models: time-varying logistic regression to identify treatment predictors, time-varying negative binomial regression for the primary composite outcome, and a Cox proportional hazards model for all-cause mortality.
Results
Following an educational intervention and a guided patient data collection, GDMT uptake increased significantly over 12 months: OMT rose from 42.1% at enrollment to 65.3% at 12 months (Figure 1). ARNi use increased from 53.4% to 74.2% in HFrEF, while SGLT2i uptake increased markedly across all phenotypes. Predictors of lower OMT achievement included older age, female sex, inpatient status, and a lower eGFR. The primary endpoint occurred in 20.7% of patients and in 22.4%, 18.2%, 27.3%, and 10.0% of patients with HFrEF, HFmrEF, HFpEF, and HFimpEF, respectively. Prognostically, OMT achievement was independently associated with a median 25% lower risk in the primary outcome (adjusted incident rate ratio [IRR] 0.86; 95% confidence interval [CI] 0.78-0.94). Specifically, patients exposed to OMT for more than 200 days had a lower risk of the primary outcome (IRR 0.75, 95% CI 0.65-0.88) than those exposed for less than 200 days (IRR 0.90, 95% CI 0.81-1.09). OMT was associated with a 27% reduction in all-cause mortality (hazard ratio 0.73; 95% CI 0.59-0.91) (Figure 2).
Conclusions
A structured implementation of rapid OMT strategies is feasible in real-world cardiology practice and is significantly associated with lower morbidity and mortality across the HF spectrum. These results reinforce the necessity of early, intensive therapy optimization and highlight the need to address organizational barriers and therapeutic inertia that currently limit the reach of foundational treatments.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.