Bucindolol hydrochloride in atrial fibrillation and concomitant heart failure

Abstract

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and it increases the risk of thromboembolic stroke and death. AF is common in patients with heart failure and reduced ejection fraction (HFrEF), affecting between 30 and 40% of patients with HFrEF. AF increases the risk of death and hospitalization in patients with HFrEF. Only two antiarrhythmic drugs (amiodarone and dofetilide) are guideline-recommended in patients with AF and heart failure (HF). Meta-analyses of studies of major trials in HF suggest that patients with AF/HFrEF do not benefit from conventional β-blockers. Bucindolol has shown promise in the treatment of patients with AF/HFrEF. We will explore how the shared pathophysiology of AF/HF is targeted by the unique pharmacology of bucindolol and review the existing data for bucindolol in AF/HF. We will explore findings that support a pharmacogenetically modulated effect of bucindolol in patients with polymorphisms in β₁-adrenergic receptor and provide an overview of ongoing studies.

Keywords:

• atrial fibrillation
• β-blockers
• bucindolol
• genotype
• heart failure

Acknowledgement

The authors thank Michael Bristow. for his critical review of the manuscript.

Financial & competing interests disclosure

J Piccini receives research grants from ARCA biopharma, Boston Scientific, Gilead, Janssen Pharmaceuticals, ResMed and St. Jude Medical, and serves as a consultant to Bayer Healthcare, ChanRx, GSK, Medtronic and Spectranetics. E Black-Maier reports no disclosures. BAS receives research support from Boston Scientific and educational support from Medtronic, St. Jude Medical, Boston Scientific and Biotronik. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors thank Michael Bristow for his critical review of the manuscript.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Atrial fibrillation (AF) and heart failure (HF) are common conditions that continue to increase in prevalence as the population ages.

• AF and HF commonly co-exist due to shared risk factors and pathophysiology.

• AF increases HF symptom burden and mortality.

• Patients with both AF and HF do not appear to benefit from currently utilized β-blockers (metoprolol, carvedilol) with respect to overall mortality.

• Data from the BEST suggest that individuals with AF, HF and specific alleles of the β₁-adrenergic receptor (β₁-389 Arg homozygotes) may benefit from bucindolol, a hypothesis currently being tested the GENETIC-AF trial.