Abstract
BACKGROUND: Heart failure (HF) is associated with high mortality and significant health care expenditures. Although guideline-directed medical therapy (GDMT) improves outcomes in patients with reduced ejection fraction, many patients receive suboptimal doses. This study compared real-world effectiveness of low versus medium/optimal GDMT doses in patients with newly diagnosed HF with ejection fraction <50%, focusing on all-cause and cardiovascular mortality. METHODS: This retrospective study included 6847 patients from the Swedish Heart Failure Registry, integrated with national health registries. Participants were categorized into 2 treatment cohorts: low dose and medium/optimal treatment dose. All-cause and cardiovascular mortality were analyzed at 3, 12, and 24 months. Cox proportional hazards models that incorporated inverse probability treatment weighting were used. RESULTS: At 24 months, medium/optimal GDMT was associated with a 23% reduction in all-cause mortality (adjusted hazard ratio [aHR], 0.77 [95% CI, 0.67-0.90], P<0.001) and a 24% reduction in CV mortality (aHR, 0.76 [95% CI, 0.62-0.93], P=0.008) compared with low-dose therapy. Mortality benefits were observed as early as 3 months, although this difference was not statistically significant after adjustment for confounding factors. These findings align with the STRONG-HF (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP [N-Terminal-Pro-B-Type Natriuretic Peptide] Testing, of Heart Failure Therapies) trial, thereby confirming the clinical efficacy of rapid GDMT uptitration in clinical practice. CONCLUSIONS: In real-world patients with heart failure with reduced ejection fraction, medium or optimal GDMT dosages significantly reduced all-cause and cardiovascular mortality at 12 and 24 months. These results underscore the importance of early and aggressive GDMT titration in improving patient outcomes and bridging the gap between clinical guidelines and real-world application.