Sildenafil for pulmonary hypertension: Dose-dependent improvement in exercise performance

Sildenafil has been widely used as an orphan drug for several years, mostly at a dose of 50 mg tid. Since a recent randomized study showed no dose–response relationship, the target dose in future will be 20 mg tid. This might, however, have a negative effect on patients being already on 50 mg tid.During the past years we usually up-titrated the sildenafil dosage in monthly intervals from 12.5 to 25 mg, and then finally to 50 mg tid. Therefore, we wondered if a dose–response relationship could be found in a group of 23 patients, in whom we had measured a 6-min walking distance (6-MWD) at all time points.The 6-MWD was virtually unchanged during the treatment with sildenafil 12.5 and 25 mg tid, respectively. However, there was a significant improvement by 34±63 and 26±47 m in the 6-MWD after increasing the sildenafil dose to 50 mg tid compared with baseline (p=0.015) and 25 mg tid (p=0.014), respectively.In conclusion, these data suggest that sildenafil has a clinically relevant dose–response relationship with a significant improvement in 6-MWD only at a dose of 50 mg tid.