Sildenafil: emerging cardiovascular indications

The discovery in 1989 of sildenafil, a highly selective inhibitor of phosphodiesterase-5 (PDE-5), was the result of extensive research on chemical agents targeting PDE-5 that might potentially be useful in the treatment of coronary heart disease. Initial clinical studies on sildenafil in the early 1990s were not promising with respect to its antianginal potential. However, the incidental discovery of its antiimpotence effect led to its approval of for the treatment of erectile dysfunction. Thereafter, several reports of adverse cardiac events in patients on sildenafil raised concerns about its safety in cardiovascular disorders. Novel therapeutic indications are emerging for sildenafil with the recent discovery that PDE-5 is expressed in various other tissues such as the arterial vasculature, including pulmonary and coronary arteries, venous vasculature, skeletal muscles, platelets, and visceral and tracheobronchial muscles. In this review we briefly summarize the pharmacology of sildenafil and the current available evidence on its potential therapeutic applications in cardiovascular disorders.