Orally active prostacyclin analogue in primary pulmonary hypertension.

Primary pulmonary hypertension is a disease of unknown aetiology that is progressive and uniformly fatal. However, substantial improvement in the duration and quality of life has been reported in patients who have received long-term intravenous prostacyclin (PGI2) infusion. But this treatment is more uncomfortable for patients and potentially more hazardous than oral therapy. On the other hand, the efficacy of oral vasodilators is not clear, apart from high-dose calcium-channel blockers in selected patients with mild symptoms. Beraprost sodium is an orally active PGI2 analogue with a stable structure due to its cyclopentabenzofuranyl skeleton. We assessed the efficacy of this drug in 12 patients with severe primary pulmonary hypertension who were unresponsive to calcium-channel blockers and inhaled nitric oxide. A diagnosis of primary pulmonary hypertension was made according to NIH registry criteria. After the patients had given their informed consent to take part, we did haemodynamic investigations with pulmonary and peripheral arterial catheters. We assessed acute responses after the first six patients had received one dose of beraprost sodium (about 2 μg/kg). Measurements were taken again after ten patients had received a daily dose of 80–180 μg for an average of 2 months. Pulmonary arterial pressure and resistance decreased by 12% and 26%, respectively (table), although one patient did respond more acutely. Three patients (cases 1, 2, and 10) did not show any improvement in their symptoms and died within 6 months. Another patient (case 4) died suddenly after 18 months. In the remaining eight patients there were improvements in functional class, as defined by New York Heart Association functional class. All these patients were still alive with the same dose of beraprost sodium during a mean of 5 (range 12–38; SD 8) months of follow-up. At the start of treatment, there were some minor complications such as flushing and headaches. A quarter of the patients with severe symptoms did not show any improvement. However, most patients responded well to long-term beraprost sodium therapy, although there were few acute responses. All our patients had a functional status of III or IV, and ten of them had a mixed venous oxygen saturation below 63%, which is associated with a poor prognosis. Thus, the long-term efficacy of beraprost sodium may be partly attributable to its effects on vascular growth or remodelling. We believe that beraprost sodium may be the first treatment option in patients with severe symptoms of primary pulmonary hypertension before resorting to intravenous PGI2 with its inherent risks and increased medical costs. But before such treatment can be recommended, further multicentre clinical trials are needed to investigate the long-term effects of the drug.