The cardiovascular effects of xanthines and selective PDE inhibitors: A risk–benefit analysis

Xanthines have been employed in the treatment of respiratory disorders since 1937, for the treatment of respiratory diseases such as COPD and asthma. However, xanthines, although effective, have a relatively narrow therapeutic window that has limited their wider use. Xanthines can also have important effects on the cardiovascular system. However, more recently, there has been the introduction of a number of selective phosphodiesterase 4 (PDE4) inhibitors for the treatment of inflammatory conditions, in particular roflumilast for the treatment of severe COPD. In addition, a number of PDE3 inhibitors have been approved for the treatment of a range of conditions, as PDE3 is widely expressed in cardiovascular tissues. The dual PDE3/4 inhibitor ensifentrine is also under development for the treatment of COPD. Here, we discuss the cardiovascular actions of xanthines and selective PDE inhibitors.