PURPOSE: Pulmonary arterial hypertension (PAH) is a progressive disease with a median survival of 2.8 years from diagnosis. Recently, the development of target-specific drugs including endothelin receptor antagonists, have improved time to clinical worsening and survival in patients with PAH. Sitaxsentan is a highly-selective endothelin-A receptor antagonist with proven efficacy in exercise capacity and quality of life in patients with PAH; however, limited data are available on the long-term survival of patients with PAH treated with this drug. Within our center in Mexico City, we sought to evaluate the effects on survival of long-term treatment with sitaxsentan, in a subset of patients from the STRIDE-3 trial.
METHODS: STRIDE-3, is an ongoing, open-label trial evaluating the long-term safety of sitaxsentan 100mg qd in PAH. Survival was assessed in patients treated with sitaxsentan for up to 4 years and rates compared with predicted survival according to the NIH equation at 1, 2 and 3 years.
RESULTS: Thirtysix patients with PAH from our department, who were included in STRIDE-3, were analysed. Of these, 33 were diagnosed with idiopathic PAH and 3 with PAH associated with connective tissue disease (mPAP 66±22mmHg, RAP 9.7±6mmHg, CI 2.6±0.9L/min/m2). All 36 patients (30 females, age range 30±11years) were treated with sitaxsentan 100mg qd long-term plus conventional therapy (mean time 148±54weeks; range 26−220weeks). At baseline, patients were in WHO functional class II, n=31; or III, n=5, and 6 minute walk distance was 320±98m. After treatment with sitaxsentan, cumulative survival in patients was 96%, 79% and 75% at 1, 2 and 3 years, respectively, versus predicted survival of 71%, 60% and 50%, based on the NIH equation (p<0.05). Four patients withdrew voluntarily from the study (withdrawal was not drug related). Five patients required combination therapy (sildenafil) because of clinical deterioration and 18 patients remain on sitaxsentan monotherapy at 3 years.
CONCLUSION: Sitaxsentan improves long-term survival in patients with PAH in WHO functional class II and III.
CLINICAL IMPLICATIONS: Sitaxsentan monotherapy is another option for target-specific treatment of pulmonary arterial hypertension.
DISCLOSURE: Tomas Pulido, Grant monies (from industry related sources) The author has been a principal investigator for some of the STRIDE studies and his institution has received research grants from Encysive.; No Product/Research Disclosure Information