NAION incidence is not increased by PDE-5 inhibitor

The review was undertaken by members of the departments of Worldwide Development and U.S. Medical Research, Pfizer, New York, and involved data from 103 company-sponsored sildenafil global clinical trials and two European observational studies: the Pfizer-sponsored prospective International Men's Health Study (IMHS) and the Prescription Event Monitoring (PEM) study conducted independently by the Drug Safety Research Unit at the University of Southampton, United Kingdom. A single case of NAION was identified in the PEM, and that translated into an unadjusted incidence rate of 2.8 cases per 100,000 patient-years.

Data from two published papers investigating spontaneous NAION in the general U.S. population were used for comparison. In those papers, the reported incidences of NAION among men age 50 years and older were 2.5 cases per 100,000 men and 11.8 per 100,000 men, respectively.

"More than 44,800 men are represented in this pooled analysis, and the occurrence of NAION is consistent with what would be expected in similarly aged men in the general population."

The Pfizer global clinical trial database contributed information on more than 13,400 men with erectile dysfunction who were treated with sildenafil in open-label and double-blind clinical trials conducted between 1993 and 2003. They provided more than 13,000 patient-years of observation.

The IMHS was conducted in Germany, France, Spain, and Sweden. It included more than 3,800 men who received a prescription for sildenafil between 2001 and 2004, and who represented nearly 3,000 patient-years of follow-up.

In the PEM, more than 28,000 men were studied who received a prescription for sildenafil through the United Kingdom's National Health Service between 1998 and 2001. They contributed approximately 35,500 patient-years of observation to the analysis.

The single case of NAION was identified in the PEM. It involved a 61-year-old patient who had multiple risk factors for NAION, including his age and a history of smoking, hypertension, and ischemic heart disease. In addition, he had been using sildenafil for more than a year before experiencing NAION.

Multiple risk factors

The occurrence of NAION in men being treated with a PDE-5 inhibitor for erectile dysfunction is not unexpected, as the two conditions share multiple risk factors. Hypertension, diabetes, hyperlipidemia, smoking, and age greater than 50 years are associated with both erectile dysfunction and NAION. In addition, men who take a PDE-5 inhibitor for erectile dysfunction are neither representative of the entire U.S. adult male population nor of the population age 50 years and older. Rather, men with erectile dysfunction represent a population with vascular risk factors that also are associated with an increased risk for developing NAION.

"Therefore, one might expect that the incidence of NAION in a large population of sildenafil-treated men might be even higher than the published estimates for the general population. Instead, the incidence in our analysis was similar to what has been reported," Sobel said.

The analysis was recently published in the International Journal of Clinical Practice (2006; 60:500-3).