Quadruple therapy for heart failure before and after electronic cardiac device implantation - are we hitting our targets?
Authors: Rode F , Jordan A , Pavlovic N , Lisicic A , Busic N , Sokol Tomic S , Manola S , Jurin I 
Published: November 2023

Abstract

Background
Quadruple therapy is currently recommended pharmacological treatment for heart failure with reduced ejection fraction (HFrEF). It consists of beta-blockers, mineralocorticoid receptor antagonists (MRA), angiotensin converting enzyme inhibitors (ACE-I) – recently suggested to be replaced with angiotensin receptor/neprilysin inhibitor (ARNI), and sodium-glucose cotransporter-2 inhibitors (SGLT2-I). Patients eligible for implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy (CRT) implantation should have therapy titrated to evidence-based target doses prior to the procedure, whenever tolerable. Compliance with guidelines as well as distinction in prescription practice before and after device implantation in the era of quadruple HFrEF therapy has not yet been fully researched.

Purpose
The purpose of this study is to evaluate the use of disease-modifying drugs in corresponding target doses in patients with HFrEF eligible for ICD or CRT implantation, prior to and after the procedure.

Methods
This is a retrospective observational study which included patients with HFrEF hospitalized for ICD or CRT implantation in a single tertiary centre from January 2021 to January 2023. Data was collected through patients' medical history and phone calls.

Results
We collected data on a total of 107 patients with HFrEF and ICD or CRT implantation. Most patients received all four classes of guideline-directed therapy before ICD or CRT implantation: beta-blockers (91,6%), MRA (86,0%), ACE-I (31,8%) or ARNI (59,8%) and SGLT2-I (59,8%). Evidence-based target doses were reached for 10,2%, 52,2%, 11,8%, 32,8% and 100% patients receiving beta-blockers, MRA, ACE-I, ARNI and SGLT2i respectively. After hospitalization for device implantation, results pointed to an increase in prescription of beta-blockers (99,1%), MRA (97,2%), and most notably SGLT2-I (87,9%), while more ACE-I (19,6%) were replaced with ARNI (75,7%). Target doses were reached for 19,8%, 72,1%, 28,6%, 37,0%, and 100% patients receiving beta-blockers, MRA, ACE-I, ARNI, and SGLT2-I respectively.

Conclusions
Most of the examined patients have been receiving all four drug classes prior to device implantation. We noticed a rising trend in recruiting novel heart failure drugs, ARNI and SGLT2-I, after the procedure. However, drug titration was non-compliant with guidelines. There was a slight improvement in up-titration of therapy after the procedure, which could be explained by more common medication adjustments by electrophysiologists during device control sessions as well as better drug tolerability after device implantation. Regardless, a minority of patients received ACE-I, ARNI and beta blockers in target doses. Despite several objective obstacles to adequate administration of disease-modifying drugs, including intolerability and patients’ non-adherence, further effort in up-titrating guideline-directed medical therapy should be applied.Therapy administration practice