The PDE5 inhibitors have been recognised by expert guidelines as first-line therapy for erectile dysfunction, based on their demonstrated record of efficacy and generally favourable safety profile in different subpopulations of men with the disease, including those with comorbidities such as diabetes, hypertension and hyperlipidaemia. The efficacy and safety of PDE5 inhibitors have been documented in both clinical trials and actual clinical practice scenarios.
Erectile dysfunction is associated with a number of comorbid conditions, including diabetes mellitus, hypogonadism, hypertension, vascular disease, dyslipidaemia and depression. According to a national representative, managed care claims database of 51 health plans and 28 million people, from 1995 to 2002, about 41.6% of men with erectile dysfunction were reported to have hypertension, 42.4% hyperlipidaemia, 20.2% diabetes mellitus and 11.1% depression. The common denominator for the majority of these men was vascular disease. The pathophysiological and clinical links between erectile dysfunction, cardiovascular disease and endothelial dysfunction have been established.
Originally, phosphodiesterase type-5 (PDE5) inhibitors were investigated as antianginal agents for patients with coronary artery disease (CAD). However, after the introduction of sildenafil in 1998, significant media attention was paid to its cardiovascular disease effects. Clinical trials for efficacy, safety and outcomes of the available PDE5 inhibitors - sildenafil, tadalafil and vardenafil - have all focused on cardiovascular disease issues, as well as the general safety profile of this class of drugs. The relationship between cardiovascular disease and erectile dysfunction has been well documented in clinical trials.
The Second Princeton Consensus Conference on Sexual Dysfunction and Cardiac Risk guidelines emphasise the importance of evaluating and managing cardiovascular disease risk factors and comorbidities in patients with erectile dysfunction.
These guidelines reinforce and underscore the vital role of primary care doctors in the screening and diagnosis of cardiovascular disease risk in erectile dysfunction patients. The consequences of missed cardiovascular disease risk assessment opportunities in this patient population are substantial. The Second Princeton Consensus divides patients with erectile dysfunction into three cardiovascular disease risk categories (low risk, intermediate or indeterminate risk, and high risk), based on their risk associated with sexual activity.
The long-term use (= 3 years) of PDE5 inhibitors in the treatment of erectile dysfunction has been proved to be safe and effective. In a study with a follow-up of 1-3 years, Sheu et al. reported that AEs associated with sildenafil treatment were mild and generally tolerable. Likewise, in a 2-year study, Stief et al. reported that most of the treatment-emergent AEs reported with vardenafil were also mild and transient, with no cardiovascular disease safety concerns.
According to the 2005 American Urological Association guidelines, PDE5 inhibitors are recommended as first-line therapy for men with erectile dysfunction. Clinical trial and post marketing surveillance data have shown good safety and tolerability profiles for PDE5 inhibitors, indicating that PDE5 inhibitors may improve erectile function safely in patients with erectile dysfunction and concomitant cardiovascular disease.
Current Safety and Tolerability Issues In Men With Erectile Dysfunction Receiving PDE5 Inhibitors