Effect of sildenafil citrate on the cardiovascular system

Sildenafil citrate is a drug commonly used to manage erectile dysfunc-tion. It is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1 H -pyrazolo[4,3- d ]pyrimidin-5-yl)-4 ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate (C 22 H 30 N 6 O 4 S). It is a highlyselective inhibitor of cyclic guanine monophosphate-specific phos-phodiesterase type 5. In late March through mid-November 1998, theUS Food and Drug Administration (FDA) published a report on 130confirmed deaths among men (mean age, 64 years) who receivedprescriptions for sildenafil citrate, a period during which >6 millionoutpatient prescriptions (representing about 50 million tablets) weredispensed. The US FDA recently reported that significant cardiovas-cular events, including sudden cardiac death, have occurred in menwith erectile dysfunction who were taking sildenafil citrate. Thesereports have raised concerns that sildenafil citrate may increase therisk of cardiovascular events, particularly fatal arrhythmias, in pa-tients with cardiovascular disease. In the past few years, the cardiacelectrophysiological effects of sildenafil citrate have been investi-gated extensively in both animal and clinical studies. According toextensive data available to date, sildenafil citrate has been shown topose minimal cardiovascular risks to healthy people taking this drug.Some precautions are needed for patients with cardiovascular dis-eases. However, the only absolute contraindication for sildenafilcitrate is the concurrent use of nitrates. This article is intended toreview sildenafil citrate’s cardiovascular effects, as well as currentdebates about its arrhythmogenic effects.