Beraprost sodium (
beraprost) is a stable, orally active
prostacyclin analogue with vasodilatory, antiplatelet and cytoprotective effects.
Beraprost acts by binding to
prostacyclin membrane receptors ultimately inhibiting the release of Ca2+ from intracellular storage sites. This reduction in the influx of Ca2+ has been postulated to cause relaxation of the smooth muscle cells and vasodilation. Data from a large, randomised, double-blind, multicentre study indicated that
beraprost was as efficacious as
ticlopidine in the treatment of patients with
peripheral arterial disease (
Buerger's disease and
arteriosclerosis obliterans). Most patients receiving
beraprost exhibited reduction of
ulcer size, reported improvement of granulation appearance of the tissue and showed improvement of
pain at rest and sensation of cold in the extremities. In a large pivotal clinical trial in patients with
intermittent claudication,
beraprost treatment was associated with statistically significant increases in
pain-free and absolute walking distances compared with those in patients receiving placebo. Statistically significant differences in the incidence of critical cardiovascular events among both treatment groups were not observed but patients receiving
beraprost were more likely to be satisfied with changes in their quality of life. However, while preliminary unpublished data from a large, phase III, placebo-controlled study in the US suggested a trend toward fewer critical cardiovascular events (no specific data presented), this study did not confirm the positive results from the European phase III trial and statistical significance was not achieved in the study's endpoints relating to exercise. A series of small, noncomparative clinical trials of patients with the rare condition of
pulmonary arterial hypertension (PAH) demonstrated that substantial reductions of pulmonary arterial pressure and resistance, increase of cardiac output, and increase of exercise capacity appeared to be associated with
beraprost therapy; however, these data are very limited and in most instances are not fully published.
Beraprost is a well tolerated agent. Overall, the main adverse events include
headache, hot flushes, diarrhoea and
nausea. However, patients with PAH showed higher incidence of adverse events than those with
peripheral arterial disease.
CONCLUSION:
Beraprost, an orally administered PGI2 analogue, is generally well tolerated and appears to be an effective agent in the treatment of patients with
Buerger's disease and
arteriosclerosis obliterans. Comparative data from a large randomised trial indicated that the
drug appears as effective as
ticlopidine in patients with these conditions. In patients with
intermittent claudication, significant benefits of
beraprost compared with placebo were reported in a randomised clinical trial; however, the use of
beraprost in these patients is not supported by recent preliminary unpublished data from a large, phase III, placebo-controlled study. Limited data suggest some efficacy with long-term
beraprost treatment of patients with PAH, where options are few and where
oral administration of the
drug could be a considerable advantage over intravenous
prostacyclin (PGI2)
therapy. Additional well-designed and, where possible, large trials with active comparators are necessary to define more precisely the place of
beraprost in the treatment of patients with PAH,
Buerger's disease and
arteriosclerosis obliterans.