Guideline-Directed Medical Therapy in the First Fortnight: Rapid Sequencing Against Traditional Titration in Heart Failure
DOI:
https://doi.org/10.5281/zenodo.22386273Keywords:
Guideline-directed medical therapy, Heart failure with reduced ejection fraction, Drug titration, Patient compliance, HyperkalemiaAbstract
Four drug classes -- an ARNI/ACEI/ARB, a beta-blocker, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor --
each reduce death and hospitalization in heart failure with reduced ejection fraction, yet real-world patients rarely receive all
four at meaningful doses within any useful timeframe. The STRONG-HF trial randomized 1,078 patients after acute heart
failure hospitalization to a high-intensity strategy reaching 100% of recommended doses by two weeks post-discharge, or to
usual care; the composite of heart-failure readmission or death by 180 days occurred in 15.3% versus 23.3% (RR 0.66, 95%
CI 0.50-0.86). PIONEER-HF and EMPULSE separately showed that starting an ARNI or an SGLT2 inhibitor in hospital,
rather than waiting for outpatient stability, is feasible and effective on their own pillar-specific endpoints. None of this comes
free: 58% of STRONG-HF's high-intensity patients had at least one safety indicator -- hyperkalemia in 28%, hypotension in
9.4%, severe renal dysfunction in 5.2% -- and a dedicated safety analysis found these indicators did not, on their own, predict
a worse outcome. Set against this is a stark real-world comparison: a 2026 Veterans Health Administration registry of 52,850
newly diagnosed patients found only 21.2% ever reached quadruple therapy, at a median of 197 days when they did. This
review sets rapid in-hospital sequencing against traditional outpatient titration on the evidence actually published, including
the monitoring burden and adherence realities that complicate any simple recommendation to move faster.
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