Phosphodiesterase-5 inhibitors: future perspectives

PDE-5 inhibitors were originally studied in cardiovascular indications but were later developed and approved for on-demand treatment of erectile dysfunction (ED). A few years ago sildenafil was approved for the treatment of pulmonary hypertension, thus renewing interest in cardiovascular applications, and tadalafil became available in once-daily formulations for erectile dysfunction management. Given the wide distribution of phosphodiesterase-5 throughout the body and its involvement in multiple functions, what can one expect in the future? To answer this we reviewed studies involving PDE-5 inhibitors that were published within the past three years and searched the US National Institutes of Health clinical trial registry for ongoing ones. PDE-5 inhibitors are being actively investigated in many disease states, with interest focusing mainly on urology and cardiovascular medicine. In urology erectile dysfunction is the primary target, followed by BPH-related lower urinary tract symptoms. As far as cardiovascular medicine is concerned, treatment of heart failure is the indication where PDE-5 inhibitors seem to be closer to clinical application but preclinical data also support a role in cardiac preconditioning.