All About Sildenafil
Sildenafil was first synthesized in 1989, and was originally intended for use in the treatment of coronary heart disease (CHD) or hypertension. However, its effects on CHD turned out to be only marginal, but patients involved in these trials reported considerable improvement in their erectile function. Thus, sildenafil was investigated further for the indication of erectile dysfunction, and has become a ‘blockbuster’ since 1998 when it was first approved in the USA. Meanwhile, more than 20 million patients have been treated with this drug, and its share in the erectile dysfunction market is around 90%. Its global efficacy in various patient groups is summarized. 
Table 1 (Click Here) provides convincing evidence of the high efficacy of sildenafil in broadspectrum erectile dysfunction populations.
All studies of sildenafil published to date show a dose-dependency of the drug-related adverse events. For example, in one of the very first sildenafil trials, the drug-related side-effect profile was as follows:
Headache Placebo 6%, sildenafil 25 mg 14%, 50 mg 21% and 100 mg 30%;
Flushing Placebo 1%, sildenafil 25 mg 13%, 50 mg 27% and 100 mg 20%;
Dyspepsia Placebo 1%, sildenafil 25 mg 3%, 50 mg 11% and 100 mg 16%;
Nasal congestion Placebo 2%, sildenafil 25 mg 1%, 50 mg 3% and 100 mg 11%;
Visual disturbances Placebo <1%, sildenafil 25 mg 2%, 50 mg 6% and 100 mg 9%.
Since the marketing of sildenafil, numerous reports, mostly in the mass media and not in the peer-reviewed cientific literature, have been published speculating on the cardiovascular safety profile of this drug. Meanwhile, many investigations have been completed, all focusing on whether sildenafil has any detrimental effects on coronary blood flow or myocardial contractility in patients with an increased cardiovascular risk profile, including patients on multimodal antihypertensive medications.
The results of these investigations can be summarized as follows. Sildenafil increased the coronary perfusion reserves by 13% in patients with CHD and increased endothelium-mediated vasodilatation and perfusion in patients with chronic heart failure. In all placebo-controlled trials of sildenafil, the incidence of serious cardiovascular events was not higher in the population treated with sildenafil compared with the placebo groups. In conclusion, to date, there is no evidence that sildenafil is responsible for any serious cardiovascular events, provided that contraindications such as concomitant nitrate or nitric oxide donor medications have been thoroughly considered.
