ABSTRACT
BACKGROUND: Pulmonary arterial hypertension (PAH) is a life threatening disease for which phosphodiesterase-5 inhibitor sildenafil is recently approved. We aimed to evaluate the efficacy and safety of tadalafil, a long acting congener of sildenafil, in treatment of PAH related to previous left to right shunt lesions. METHODS: In this blinded, cross over study, 11 patients with severe PAH related to congenital left to right shunt lesions (Eisenmenger syndrome) were randomly assigned to tadalafil (20 mg daily) or placebo for 4 weeks period, separated by a wash out period of at least 2 weeks. They were symptomatic with a six minute walk distance (6MWD)>or=50 m. The change in 6MWD, echo-Doppler determined pulmonary artery systolic pressure (PASP), WHO Class and modified Borg Dyspnea Index (BDI) were assessed after each therapy. RESULTS: Eight patients who completed the study protocol were analyzed. Tadalafil was associated with a significant increase in 6MWD (mean 409.25 SD 40.25 m vs 319.37 SD 42.39 m, p<0.0001), reduction in PASP (88.75 SD 23.26 mmHg vs 109.5 SD 23.78 mmHg, p<0.0001), improvement in BDI (4.62 SD 2.56 vs 6.37 SD 2.61, p=0.021) and WHO Class (6 patients vs 2 patients), compared to placebo. Tadalafil was well tolerated with no significant untoward effects. CONCLUSIONS: Tadalafil, in patients with PAH related to previous congenital left to right shunt lesions, lead to a significant improvement in exercise capacity (6MWD), PASP and WHO Class with reduced perceived exertion and was well tolerated.