Reevaluating the role of phosphodiesterase inhibitors in the treatment of cardiovascular disease.

First developed for clinical use in the late 1980s, the phosphodiesterase inhibitors were found to increase the levels of the ubiquitous second messenger cyclic adenosine monophosphate and could effect changes in vascular tone, cardiac function, and other cellular events. After several early studies using high doses of phosphodiesterase inhibitors in patients with severe heart failure suggested adverse consequences, they fell out of favor. However, recent investigations of phosphodiesterase inhibitors in patients with intermittent claudication have demonstrated profound benefits. Furthermore, these agents have proven useful in prevention of cerebral infarction and coronary restenosis, and their use in the treatment of heart failure is being reevaluated. The reemergence of phosphodiesterase inhibitors can be attributed to a better understanding of dosing and drug-specific pharmacology, the use of concomitant medications, and a recognition of unique ancillary properties; however, their use still requires caution.