Intensive titration for elderly patients with heart failure

Guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF) relies on quadruple therapy, including beta-blockers (BB), angiotensin receptor-neprilysin inhibitors (ARNi), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i). Elderly patients with HF represent a high-risk population and often face therapeutic inertia but also more adverse events. We aimed to assess the efficacy and safety of an intensive titration program (ITP) for elderly HFrEF patients.

We conducted a prospective, single-center, observational study including HFrEF patients aged ≥ 75 years managed with an ITP between January 2024 and February 2025. The primary outcome was the prescription rate of quadruple GDMT at 3 months, irrespective of dose. Secondary outcomes included prescription of quadruple therapy at ≥ 50% of GDMT target doses and identification of predictors of limited implementation. Safety outcomes included adverse events occurring during titration and within 3 months after completion.

Sixty-four patients were included (Median age 80 years, 70% male, 28% diabetes, median eGFR 50 mL/min). The mean titration period was 100 days (14 weeks). At 3 months, 33% of patients were prescribed quadruple therapy, with 5% achieving ≥ 50% of the recommended target dose in each drug class. Target dose achievement improved across all drug classes between baseline and 3 months: ARNi (1% vs. 31%), MRA (1% vs. 14%), and BB (3% vs. 5%) (all P <0.05). These improvements were associated with short-term clinical and biological benefits (NT-proBNP reduction, improved left ventricular ejection fraction). Reported adverse events included symptomatic hypotension (8% with treatment discontinuation) and acute kidney injury (8 % requiring hospitalization). Older age and chronic kidney disease were associated with limited initiation of quadruple therapy.

An intensive titration program for HFrEF therapy appears feasible and relatively safe in elderly patients.