Higher intensity of guideline-directed medical therapy is independently associated with a more favourable biomarker profile in real-world heart failure patients

Background

Guideline-directed medical therapy (GDMT) based on four pharmacological pillars: beta-blockers, MRAs, SGLT2 inhibitors, and RAS inhibition represents the cornerstone of contemporary management of chronic heart failure (CHF). Although the prognostic benefit of individual drug classes is well established, the relationship between the overall intensity of GDMT and biomarkers reflecting biological disease activity in real-world clinical practice remains insufficiently characterised.

Methods

We performed a prospective observational analysis of 304 patients with CHF followed at a specialised tertiary centre. Patients were stratified according to the number of concurrently prescribed GDMT components into four groups: 0–1 component (n = 31), 2 components (n = 55), 3 components (n = 84), and 4 components (n = 134). Baseline levels of SCN, NT-proBNP, and hsTnI were assessed. Biomarker values are presented as median with interquartile range. Between-group comparisons were performed using the Kruskal–Wallis test and an ordinal trend test. Multivariable analyses were subsequently conducted with adjustment for age, sex, BMI, and LVEF.

Results

With increasing GDMT intensity, patients were significantly younger, with median age decreasing from 73 years (66–79) in the 0–1 component group to 67 years (60–73) in the complete GDMT group (p for trend = 0.006). The proportion of male patients increased from 71.0% to 85.1% across GDMT strata (p for trend = 0.021), while median BMI rose from 26.1 kg/m² (23.4–29.0) to 30.1 kg/m² (27.2–33.8; p for trend = 1.38 × 10⁻⁵). In contrast, LVEF was lower in more intensively treated patients, with median values declining from 35% (30–40) to 30% (25–35; p for trend = 0.011).

SCN levels demonstrated a significant decreasing trend with increasing GDMT intensity, with median concentrations of 57.7 ng/L (40.7–88.8) in patients receiving 0–1 component, 48.6 ng/L (35.6–77.8) with 2 components, 59.2 ng/L (40.8–83.8) with 3 components, and 46.3 ng/L (33.3–72.5) in those on complete GDMT (p for trend = 0.041). A similar but less pronounced pattern was observed for NT-proBNP, with median values decreasing from 1572 ng/L (788–8402) to 1003 ng/L (393–3292; p for trend = 0.016). The most robust association was found for hsTnI, which declined from a median of 36.1 ng/L (21.8–373.7) to 20.9 ng/L (10.5–67.4) across increasing GDMT intensity (p for trend = 0.002). After multivariable adjustment, GDMT intensity remained independently associated with lower hsTnI levels and preserved a significant trend with SCN, whereas the association with NT-proBNP was attenuated.

Conclusions

In patients with CHF, higher intensity of GDMT is associated with a more favourable biomarker profile despite lower LVEF in intensively treated individuals. These findings suggest that the cumulative burden of evidence-based pharmacotherapy, rather than individual drug classes considered in isolation, better reflects biological modulation of disease activity in CHF.Figure 1For image description, please refer to the figure legend and surrounding text.