Feasibility, efficacity and safety of a fast up-titration program of heart failure treatments in real-life practice

Introduction

Guideline-directed medical therapy (GDMT) of chronic heart failure (HF) associates four drugs: Beta-Blockers (BB), Angiotensin Receptor-Neprilysin Inhibitor (ARNi), Mineralocorticoid Receptor Antagonists (MRA) and Sodium-Glucose co-Transporter 2 (SGLT2) inhibitors. Their initiation and implementation should begin quickly from the diagnostic, but therapeutic inertia leads to higher mortality and hospitalisation rates.

Objective

To evaluate the feasibility, efficacity and safety of an intensive and fast up-titration program of GDMT at three months, limiting factors to GDMT up-titration and factors associated with poor outcomes in this population.

Method

We retrospectively included all patients participating to our up-titration program from January 2021 to September 2022. Patients were followed every 2 weeks by consultation (on-site or teleconsultation). We collected clinic-biological, echocardiographic data and GDMT doses at the enrolment, at the end of the up-titration, and three months later.

Results

222 patients were enrolled. The mean titration duration was 10 weeks (± 57 days). The proportion of patients with full dose of ARNi was 1.4% at day one and 44.6% at three months, 4.5% then 32.7% for MRA, and 5% then 15.4% for BB. 90% of the population was treated with SGLT2 inhibitor at 3 months (Fig. 1). Consecutively, the proportion of patients with loop diuretics decreased from 70.7% to 42.9%. In the meantime, we observed a significant improvement of the dyspnoea (from 85.4% to 45.7% of patient in class II of the NYHA and from 10.8% to 51.1% of patients in class I), the LVEF (from 30.8% to 45.2%) and a decline of the NT-proBNP (from 1322 to 484 pg/ml). Associated adverse events were hypotension (15.3%), acute renal impairment (14.9%) and hyperkalaemia (6.8%) without difference between on-site and teleconsultation groups. Limiting factors to up-titration of ARNi and MRA were advanced age, low eGFR and high value of the NT-proBNP (> 1000 pg/ml). 6 patients died during the study (2.7%) and 16 were readmitted in hospital for HF (7.2%). Persistent treatment with loop diuretics at the end of the up-titration was identified as a poor prognostic, whereas prescription of ARNi was identified as a protective factor.

Conclusion

A fast up-titration program is feasible, efficient and safe in real-life practice. Combination of on-site and teleconsultation seems appropriate and should be proposed to fight therapeutic inertia without increasing adverse events.