The use of β-blockers in patients with heart failure and comorbidities: Doubts, certainties and unsolved issues.

β-blockers represent a mainstay in the pharmacological approach to patients affected by heart failure with reduced ejection fraction (HFrEF). However, underuse of this class of drugs is still reported, especially in the presence of cardiovascular and non-cardiovascular comorbidities, even if they are not contraindications for prescription of a β-blocker. The prognostic benefit of β-blockers is relevant in the presence of comorbidities, and achievement of the maximum tolerated dose is an important goal to increase their favorable prognostic role. The aim of the present review is to analyze the available evidence on the use of β-blockers in HFrEF patients with the most common comorbidities. In particular, we will discuss the role and most appropriate beta-blocker in patients with pulmonary disease (bisoprolol, metoprolol, nebivolol), diabetes (carvedilol and nebivolol), atrial fibrillation (all indicated for rate control, with metoprolol as the first choice followed by bisoprolol, nebivolol, and carvedilol), erectile dysfunction (bisoprolol and nebivolol), peripheral arterial disease (nebivolol), and other conditions, in order to clarify the correct use of this class of drugs in the clinical practice.