Phosphodiesterase-5 inhibitors as novel cardioprotective agents: have we reached threshold for large-scale clinical trials?

We read with great interest the compelling findings of Andersson et al demonstrating strong association between on-demand use of phosphodiesterase-5 (PDE5) inhibitors (PDE5is) and a reduction in cardiovascular mortality and heart failure hospitalisation in patients followed up following their first myocardial infarction (MI). We previously reported in Heart a similarly strong association between PDE5i use and reduced mortality in a cohort of patients with type 2 diabetes and attendant high cardiovascular risk.1 In our study, we showed that the association was stronger in patients with prior MI, supporting a cardioprotective action, although we were unable to draw conclusions about underlying mechanisms of protection.

As the authors concede, and in similarity to our study, the observational nature of their work and the presence of unmeasured confounding factors (eg, marital status, physical activity, diposable income and educational attainment) make it impossible to establish concrete conclusions. Even so,...