Determinants of long-term survival in the guideline-directed era: real-world evidence on pharmacological persistence and up-titration

Background

Despite robust evidence supporting Guideline-Directed Medical Therapy (GDMT) for heart failure, it’s implementation and therapeutic persistence in routine clinical practice remain a formidable challenge. There is a critical need to document how the transition to the "four pillars" of therapy translates into long-term survival in real-world settings.

Objectives

This study aimed to evaluate the longitudinal evolution of pharmacological prescription patterns and 2-year survival rates within a contemporary cohort of 936 patients following a structured optimization protocol.

Methods

Prospective observational cohort of 936 HF patients under cardiology follow-up. Prescription proportions for the "four pillars" of therapy ACEi/ARB/ARNI, Beta-blockers (BB), Mineralocorticoid Receptor Antagonists (MRA), and SGLT2 inhibitors (SGLT2i) alongside adjunctive therapies (Diuretics, Digitalis, ASA), were analyzed at three time points: baseline, 1 year, and 2 years. Differences in proportions were assessed using trend tests, and survival was tracked longitudinally.

Results

A significant and progressive optimization of treatment was observed over the 2-year period:

Cornerstone Therapies: The uptake of SGLT2i demonstrated the most striking growth, surging from a marginal 3.3% at baseline to 61.5% at 2 years (p<0.0001).

GDMT Scaling: ARNI/ACEi/ARB utilization increased from 44.6% to 68.6% (p<0.001), while BB prescription scaled from 23.4% to 62.1% (p<0.001). MRA usage also rose significantly from 18.3% to 49.1% (p<0.001).

Survival by Cohort: Overall survival was highest among groups with greater adherence to GDMT. At 2 years, the SGLT2i group reached a 95% survival rate, followed by the BB group at 92.4%. Conversely, patients requiring persistent diuretic therapy exhibited lower survival (89.4% at 2 years), suggesting a profile of increased congestion or clinical severity.

Therapeutic De-escalation: A significant reduction in Digitalis use was observed (6.4% to 2.1%, p<0.05), aligning with contemporary recommendations to prioritize disease-modifying therapies.

Conclusions

In a contemporary Mexican real-world cohort, structured implementation and up-titration of quadruple therapy was associated with >90% 2-year survival, with rapid adoption of SGLT2i as the most prominent shift. These findings support early, proactive GDMT optimization to maximize long-term outcomes in HF.Survival folllow-up by drug therapyFor image description, please refer to the figure legend and surrounding text.