Pharmacotherapy of patients with heart failure and atrial fibrillation: let's get the evidence!

New 2024 ESC guidelines have focused on the optimal treatment of atrial fibrillation (AF). 1 The established AF-CARE framework 1 suggests that AF treatments are more effectiv e when comorbidities are properly managed.Heart failure (HF) is one of the most important comorbidities.The two entities are actually mutually dependent: patients with concomitant HF and AF have even worse symptoms and a poorer prognosis. 2Due to this complex clinical and pathophysiological interplay, we would like to highlight the significant gaps of evidence in the pharmacotherapy in these patients.Regarding the benefits of the four pillars of treatment of HF with reduced ejec tion frac tion (HFrEF) defined in the 2021 ESC guidelines, 2 evidence from the subgroup of patients with HFrEF and AF is limited.This holds true mainly for drug therapies with a longstanding tradition.Bet a-blockers , as an example, are known to be an important component of AF rate control but also constitute a cornerstone of HFrEF therapy. 2 In a meta-analysis assessing HFrEF patients with sinus rhythm vs. AF, 3 beta-blocker therapy resulted in a significant reduction in all-cause mortality only in patients with sinus rhythm. 3Regarding angiotensin-converting-enzyme inhibitors (ACE ) inhibitors, there is a lack of secondary AF-related analyses from large prospective studies.In more recent HF trials assessing angiotensin receptor-neprilysin inhibitor 4 and sodium/glucose cotransporter 2 (SGLT2) inhibitors, the HF/AF subgroup was explicitly investigated and efficacy was also clearly demonstrated, 4 , 5 yet questions regarding details such as AF characteristics remain unanswered.At a time when we are trying to provide more personalized treatment in HF and have increasingly achieved this, e.g. for concomitant renal insufficiency and diabetes, we need to devote more attention to AF as one of the most common comorbidities.In addition to detailed subgroup analysis, we also need to ask questions regarding the type of AF, potential sinus rhythm during the trial, and treatment of AF or even pace-and-ablate that may simulate sinus rhythm for the left ventricle.Does it make a difference whether AF is already present at study baseline or whether its onset occurs during the observation period?HF specialists and electrophysiologists should join forces to advance more personalized and precision medicine.Let's get the evidence!