PURPOSE: Tadalafil is a potent PDE5 inhibitor licensed for use once daily. When administered for erectile dysfunction, duration of effect is 18 to 72 hours. Our purpose was to investigate if this effect on the PDE5 receptor in the corpus cavernosum could be replicated in the pulmonary vasculature. We gave the drug every second day in a clinical open label prospective study in order to see if this could match the results already seen in once daily dosage for pulmonary hypertension.
METHODS: 22 patients matched for age and sex were included and given either 20 or 40 mg tadalafil once every second day. The right venticular pressure was measured indirectly by the tricuspid jet on UCG. A blood gas sample was drawn and a maximal ECG exercise test was performed with SaO2 of 85% as the lower limit for break off. These examinations were then repeated after 12 weeks.
RESULTS: From a mean right ventricular pressure of 71.5 mm Hg, (range 45-120 mm Hg), patients achived a mean reduction of 11.3% or 8 mm Hg. If 4 non-responders, equally found in both treatment groups, are excluded, that reduction rises to 15.1% or 10.5 mm Hg. (Range 5.7 % to 33.3 %). Exercise capacity rose from a mean of 82.6 W with 7.4% or 6.1 W. If 4 non-responders are excluded the rise is 9.6 % or 7.1 W.(Range 0.6% to 28.4%)
CONCLUSIONS: Tadalafil given every second day produces clinically significant results, either measured as a reduction in right ventricular pressure or as a gain in exercise capacity. These results are at least on parity with sildenafil, where a reduction of 2.7 to 3.9 mm Hg in right ventricular pressure was seen and where exercise capacity was measured with a 6MWT with a mean gain of 26 to 50 metres, or 7.5 to 14.5 %. Tadalafil has in other studies where 40 mg has been given daily, shown a reduction in right venticular pressure of 4.3 mm Hg and a gain in exercise capacity measured as 6MWT of 26 m or 7.6%.
CLINICAL IMPLICATIONS: A dosage of 20 to 40 mg every second day of tadalafil is a significant improvement when it comes to patient compliance and the reduction of cost for society, especially compared to sildenafil and the need for dosing three times daily. This study shows that the extended duration of effect on the corpus cavernosum may exist in the pulmonary vasculature as well, thereby enabling a treatment regime with tadalafil every second day and a significant reduction in treatment cost compared to sildenafil 20 to 40 mg three times daily or tadalafil 40 mg daily. The cost-benefit per patient-year in Sweden is from USD 7500 to 18800.
DISCLOSURE: The following authors have nothing to disclose: Stefan Rustscheff, Jan Wilske, Leif Bjermer