Early Initiation of Guideline-Directed Medical Therapy Improves Outcomes in Heart Failure with Reduced Ejection Fraction Patients without Significant Risk of Nephrotoxicity.

Background: Current evidence supports the early initiation of all guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF), but clinical inertia persists in real-world practice. Methods: Clinical data of 343 HFrEF patients hospitalized from January 2018 to December 2019 were collected, and they were followed for at least 3 years. We analyzed the benefits of optimizing GDMT at hospital discharge, the reasons for underprescription of GDMT, and factors associated with different outcomes after multivariate adjustments. Results: Starting at least 3 pillars of GDMT at hospital discharge significantly reduced the risks of all-cause mortality, cardiovascular (CV) death, and heart failure hospitalization (hazard ratio = 0.22, 0.21, 0.28, respectively; all p < 0.001). Renal impairment was the major factor associated with the non-optimization of GDMT, and 78.4% of patients receiving fewer than 3 pillars of GDMT had a baseline chronic kidney disease stage 3-5. However, the prescription of GDMT was not associated with any observable risk of adverse renal outcomes. Conclusions: This study demonstrated the CV benefits and safety regarding renal outcomes with the early initiation of GDMT in HFrEF patients. Efforts should be made to address the disparity between evidence-based medicine and daily practice.