Abstract 2108: Sitaxsentan Treatment In Patients With Eisenmenger Syndrome
Background: Untreated, patients with Eisenmenger Syndrome (ES) develop progressive cyanosis and dyspnea on exertion resulting in a poor long-term outcome. There is currently no cure for ES once established. Furthermore, the data on use of targeted treatment for PAH in ES patients is limited. We sought to determine whether treatment with sitaxsentan (SITAX), a selective endothelin-A receptor antagonist, is safe and effective in ES patients.
Methods: A retrospective chart review was performed on a cohort of consecutive patients(pts) with ES (ASD-7, VSD-6, AVC-1, PDA-1) treated with SITAX. Baseline data was compared to short-term (12 weeks) and long-term (~1yr) follow up (f/u) data. Statistical analysis was performed using the paired t and Bowker’s tests for comparisons. Data are presented as mean +/− S.D.
Results: Fourteen ES pts (10 female: 4 male; age 27±11yrs) initiating SITAX therapy (100 mg po qd) at Columbia Univ., between 2/02 and 12/06 were evaluated at baseline, 12 wks, and long-term (mean time to f/u 11±4mos;range 6 –13mos;n=12). In 2 pts, SITAX was added to another chronic PAH therapy (1 SQ treprostinil, 1 sildenafil and ventavis); 1 other pt who started sildenafil at wk 8 was not included in the hemodynamic analysis. Mean resting SaO2 was 89±7% (n=14) with no significant change at wk 12 (89±8% n=14) or at late f/u (88±10%; n=12). Hemoglobin also remained unchanged. The 6 minute walk distance was 387±77meters(m) at baseline, 416±107m at 12 wks and 414±101m at long-term f/u (n=14; p=NS). In the 8 pts with serial catheterization data, PVRi was 30±21U*m2 at baseline and 20 ±11 U*m2 at late f/u (p=0.09). The PVR/SVR ratio was 1.0±0.7 at baseline and 0.6±0.4 at f/u (n=7; p=0.04). There was no significant difference in baseline PVR for those with/without late f/u data. 91% of pts had no change or improvement in WHO functional class at late f/u (n=11;p=NS); 1 pt discontinued SITAX after 12 wks due to inadequate response. No deaths occurred during the f/u.
Conclusion: In pts with ES, SITAX treatment appears safe with no significant decrease in resting Sa02 at early or late-term f/u. With initiation of SITAX there was improved PVR/SVR ratio consistent with pulmonary selectivity in these pts. There may also be favorable effects on exercise capacity. Further studies are warranted.