Abstract

Heart failure (HF) and atrial fibrillation (AF) are major global health challenges with rising prevalence and significant morbidity, mortality, and healthcare burden. Despite advances in HF management, AF remains a critical comorbidity that worsens outcomes and requires ad hoc treatment strategies, increasing the risk of non‐adherence and side effects. While rhythm control strategies in AF have gained attention for their prognostic benefits in HF, the pharmacological treatment of HF in patients with AF, including the benefit of rhythm versus rate control, remains underexplored. The relationship between HF and AF lacks sufficient evidence and targeted research to assess the optimal treatment strategies. This narrative review critically examines current HF pharmacotherapy in the context of AF, focusing on the four cornerstone treatments and modifiers of prognosis for HF with reduced ejection fraction: beta‐blockers, angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/sacubitril‐valsartan, aldosterone antagonists, and sodium–glucose co‐transporter 2 inhibitors. Although these therapies are well‐established in HF patients, their efficacy in patients with concomitant AF requires further prospective investigation. The unique challenges posed by AF, including arrhythmia‐induced remodelling and cardiomyopathy, necessitate a more individually tailored treatment. We also highlight critical knowledge gaps and the need for dedicated clinical trials specifically assessing HF therapies in AF subgroups, such as paroxysmal, long‐standing persistent and permanent AF, and the benefit of heart rate and rhythm control strategies. The future of precision medicine in HF‐AF management lies in bridging these evidence gaps through targeted research and interdisciplinary collaboration.