Effects of Beraprost Sodium, an Oral Prostacyclin Analogue, in Patients with Pulmonary Arterial Hypertension: A Randomized, Double-Blind, Placebo-Controlled Trial - ALPHABET

Jun 25, 2003
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Date Published:
01/01/2002
Date Updated:
06/25/2003
Original Posted Date:
06/25/2003
References

Description:

The goal of this study was to assess the safety and efficacy of beraprost, an orally active prostacyclin analogue, in patients with pulmonary arterial hypertension (PAH) NYHA functional class II and III.

Study Design

Study Design:

Patients Enrolled: 130
NYHA Class: class II and III
Mean Follow Up: 12 weeks
Female: 65

Patient Populations:

PAH

Drug/Procedures Used:

A double-blind, placebo controlled trial of beraprost in 130 patients with PAH. Initial dose of 20 micrograms 4 times daily was titrated weekly as tolerated by 20 micrograms to a maximum of 120 micrograms 4 times daily for a total of 12 weeks. The primary end point was change in exercise capacity on the 6-minute walk test (6-MW), and secondary end points were change in the Borg Dyspnea Index (BDI), hemodynamic paramaters and the NHYA class.

Principal Findings:

The average age was 45 years, 65% were women, about half were NYHA class II, baseline mean RA was 8mm Hg, mPA 60 mm Hg, CI, 2.4L/min/m2, PVRI 23 Wood units/m2 and 6-MW distance averaged 370 m. The mean study beraprost dose was 80 micrograms 4 times daily. At 12 weeks, there was a significant improvement in the BDI. The difference between groups for the 6-MW was 25.1 m [95% CI 1.8-48.3, p=0.03]. In the subgroup with PPH, the difference was 46.1 m vs. 11 m in the PAH with congenital heart portal PAH and collagen disease. There was no effect of treatment on hemodynamics or NYHA class at 12 weeks. Side effects of beraprost included headache, flushing, jaw pain, diarrhea, leg pain and nausea, which limited dose titration.

Interpretation:

Among NYHA functional class II and III patients with PAH and in particular those wtih PPH, beraprost improves exercise capacity and symptoms. That there was no change in cardiovascular hemodynamics is quite disappointing, as was that the benefit was limited to the PPH patients. IV epoprostenol improves hemodynamics and functional class and reduces mortality primarily by inducing remodeling of the pulmonary arteries. It is likely the dose of oral beraprost over 12 weeks was not adequate to induce remodeling but possibly could occur with further titration over time.

References:

J Am Coll Cardiol 2002;39:1496–502.

Keywords: Nausea, Epoprostenol, Hypertension, Pulmonary, Diarrhea, Dyspnea, Collagen Diseases, Pulmonary Artery, Headache, Hemodynamics, Exercise Test


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