Evolving trends in treatments, morbidity, and mortality in heart failure: 30 years of data from the italian network of heart failure (IN-HF) registry
C Basile, S Carigi, M Gori, M Marini, M Iacoviello, M Gorini, F Orso, L Tavazzi, A P MaggioniAbstract
Background
Heart failure (HF) management has undergone significant transformations over the past three decades, driven by evolving pharmacological and device-based guidelines. Historical data from the US and Sweden have shown conflicting mortality trends over the years for patients with HF. There is, therefore, uncertainty about whether the prognosis for HF has improved over the years, and contemporary real-world evidence is needed.
Purpose
To describe the evolving trajectories of clinical characteristics, therapeutic strategies, and mortality in HF patients over a 30-year period in a large unselected Italian cohort.
Methods
This analysis included data from the IN-HF registry, comprising 37,523 patients with chronic or acute HF managed at multiple Italian centers from 1995 to 2025. The cohort was divided into four distinct clinical eras based on evolving guideline recommendations: the pre-beta-blocker era (1995-2000), the beta-blocker and renin-angiotensin system inhibition era (2001-2011), the addition of mineralocorticoid receptor antagonists and later sacubitril/valsartan to the HF medical therapy era (2012-2020) and the four-pillar era of medical treatment, including sodium glucose co-transporter type 2 inhibitors (2021-2025). Year-by-year trends in HF categories, comorbidities, and treatment patterns were reported with p-values for trends, whereas the analysis of 4-year all-cause mortality employed multivariable-adjusted Cox proportional hazards models.
Results
Over time, patients aged >75 years increased from 11% to 40%, women from 24% to 35%, patients with HF with preserved ejection fraction from 18% to 33%, while patients with HF with reduced ejection fraction decreased from 62% to 45%, (all p for trend <0.001). Regarding comorbidities, the prevalence of ischemic heart disease declined from 42% to 31%, atrial fibrillation increased from 18% to 35%, anemia from 23% to 37%, and stage III chronic kidney disease from 29% to 41% (Figure 1) (all p for trend <0.001). Treatment trajectories indicated significant uptake of all guideline-directed medical therapies (GDMTs) over the years, with decreasing use of digoxin, nitrates, and ivabradine (all p for trend <0.001), and stable use of loop diuretics (Figure 1). Over a median follow-up of 441 days [interquartile range 246-1461], 5230 (13.9%) all-cause mortality events occurred. Compared with the 1995-2000 reference era, all-cause mortality declined consistently over the years, with the four-pillar era showing the largest reduction (hazard ratio 0.37, 95% confidence interval 0.30-0.46) (Figure 2).
Conclusions
Over the past 30 years, the Italian HF population has aged and become more complex, with an increased prevalence of comorbidities. Despite these risks, the progressive implementation of GDMTs has contributed to a significant reduction in all-cause mortality, with the greatest survival benefits observed in the current four-pillar era.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.