Dose-response Effect of PDE-5 Inhibitors

Efficacy. In general, the degree of efficacy in improving erectile function (e.g. scores for the IIEF “EF domain” or individual item scores, SEP-Q2/Q3 scores, percentage of patients who responded “yes” to GAQ-Q1) tended to increase with the doses of PDE-5 inhibitors. The observed trends were either numerical or statistically significant. Formal statistical test results for differences in efficacy between dose-specific arms for PDE-5 inhibitors were not provided in many trial reports, which complicated the interpretation. The observed dose-response trends in efficacy were less obvious for tadalafil trials, in which the degree of improvement in erectile function was numerically similar in patients who received three doses of tadalafil (20 mg, 10 mg, and 5 mg). According to our meta-analyses, in sildenafil trials the proportion of patients with improved erection (GAQ-Q1) was greater for men who received 50 mg compared with those who used a 25 mg dose. The difference for the corresponding proportions between 50 mg and 100 mg groups favored the higher 100 mg dose but was not statistically significant. Although the mean IIEF “EF” domain score and the proportion of “yes” responses to GAQ-Q1 among patients treated with vardenafil favored the 20 mg dose over the 10 mg dose, the differences did not reach the statistical significance.

Harms. The incidence of any all-cause adverse events in sildenafil (25 mg versus 50 mg versus 100 mg) and vardenafil (5 mg versus 10 mg versus 20 mg) trials had a numerical pattern of dose-dependence, indicating that adverse events occurred more frequently at the higher doses. The dose-response pattern for the effect of tadalafil (10 mg versus 20 mg) was not obvious. The meta-analyses conducted on vardenafil trials showed an increased risk of any adverse events in patients treated with the 20 mg versus the 10 mg dose. The difference for the proportion of patients with serious adverse events between the two doses of vardenafil was not statistically significant. Neither the rate of withdrawal resulting from adverse events nor specific adverse events (i.e., headache, flushing, dyspepsia) differed between the two doses. The meta-analyses of sildenafil trials revealed no statistically significant differences in the incidence of specific adverse events (i.e., headache, flushing, or visual disturbances) between the 25 mg, 50 mg, and 100 mg sildenafil groups. The meta-analysis of tadalafil trials found a statistically significant increase in the risk of any adverse events for patients in the 20 mg group relative to those in 10 mg group.