Mid-term efficacy of beraprost, an oral prostacyclin analog, in the treatment of distal CTEPH: a case control study.

Background: Prostanoids are a well-established therapy for pulmonary arterial hypertension (PAH), and observational studies suggest their efficacy even in chronic thromboembolic pulmonary hypertension (CTEPH) patients.

Objective: To compare the effects of 6 months of treatment with beraprost, an orally-active prostacyclin analog, in patients with distal CTEPH and PAH.

Design: Case-control study.

Population: Sixteen patients with severe pulmonary hypertension (NYHA II-IV), eight with distal CTEPH matched with eight patients with idiopathic PAH for similar effort tolerance.

Methods: All patients were in stable clinical and hemodynamic condition for 3 months with maximal standard therapy. During the titration phase (4 weeks) beraprost was increased to maximal tolerated dose (mean daily dosage: CTEPH 275 +/- 47 microg, PAH 277 +/- 47 microg) in adjunction of standard therapy, patients were followed-up for 6 months.

Main Outcome Measures: World Heart Organization (WHO) functional class, exercise capacity measured by distance walked in 6 min, and systolic pulmonary pressure (echocardiography), were evaluated at baseline, and at 1-, 3- and 6-month interval.

Results: At 6 months WHO class decreased significantly in both groups (CTEPH from 2.7 +/- 0.6 to 2.0 +/- 0.24, p < 0.05; PAH from 3.0 +/- 0.26 to 2.1 +/- 0.25, p < 0.05), similarly the 6-min walk distance increased significantly from baseline (CTEPH from 312 +/- 31 to 373 +/- 29 m, p < 0.003; PAH from 303 +/- 31 to 347 +/- 29, p < 0.0003). Systolic pulmonary artery pressure showed a trend toward lower value (CTEPH from 85 +/- 7 m to 81 +/- 6 mm Hg, p = NS; PAH from 89 +/- 7 to 82 +/- 5, p = NS). During the observation period we did not have any death. The drug was well-tolerated with minor side-effects.

Conclusion: In patients with CTEPH beraprost had similar mid-term clinical and hemodynamic improvements than in patients with PAH.