To evaluate the long-term efficacy of Sitaxsentan treatment in patients with severe pulmonary arterial hypertension (PAH).
We included patients with idiopathic PAH (IPAH), PAH associated with congenital systemic-to-pulmonary shunts (CSPS) and PAH associated with connective-tissue disorders (CTD), all treated with 100 mg of Sitaxsentan daily. We analyzed baseline hemodynamic parameters, 6-minute walk distance (6MWD), Borg Scale (BS), World Health Organization (WHO) functional class and time for clinical worsening. With exception of the hemodynamic parameters, all the other variables were measured every 6 months and registered yearly for 6 years. Variables are expressed with a mean ± SD. Differences between years were evaluated by repeated-measures ANOVA and a T test was used for independent groups evaluation. Statistical significance was accepted as a p ≤ 0.05.
Fifty-seven patients with severe PAH were reviewed and divided into groups. GROUP1 included 34 patients (59.6%) with IPAH and 5 patients (8.77%) with PAH associated with CTD. GROUP2 included 18 patients (31.5%) with PAH associated with CSPS. Baseline mean pulmonary arterial pressure (MPAP) was 67.21 ± 20.93 vs. 73 ± 20.6 mmHg, respectively. Basal to 6-year 6MWD: 386 ± 113 m vs. 369 ± 113 m for GROUP1, and 316 ± 76 m vs. 326 ± 60 m for GROUP2. Basal BS to 6-years BS: 3.03 ± 2.15 vs. 4.06 ± 2.86 for GROUP1, and 4.00 ± 1.79 vs. 3.81 ± 2.23 for GROUP2. Finally basal to 6-year functional class: 1.65 ± 0.61 vs. 1.47 ± 0.51 for GROUP1, and 1.94 ± 0.56 vs. 2.06 ± 0.56 for GROUP2. None of the variables were statistically significant. Eleven patients died in total. Four patients were discontinued in GROUP1 and 4 patients were initiated with PDE-5 inhibitor (sildenafil) combined therapy.
Sitaxentan is an effective medication to prevent clinical worsening in patients with severe PAH.
Despite of the dramatic expansion of new pharmacotherapies, approved treatments for PAH are still limited. Sitaxsentan is a selective Endothelin-A receptor antagonist currently approved by the FDA for PAH treatment. It has demonstrated an improvement in the 6MWD and functional capacity in the short term respectively.
Maria-Dolores Hernandez de Diego, No Financial Disclosure Information; No Product/Research Disclosure Information