[Short- and long-term effects of the new oral prostacyclin analogue, beraprost sodium, in patients with severe pulmonary hypertension].
Prostacyclin (PGI2) is a bioactive substance produced by vascular endothelial cells, which exerts powerful vasodilative and anti-platelet actions. Patients with pulmonary hypertension have an imbalance between vasodilative PGI2 and vasoconstrictive thromboxane B2 (TXB2). Treatment with vasodilative agents is essential for such patients. Continuous intravenous infusion of PGI2 is an effective treatment of primary pulmonary hypertension in terms of exercise capacity and survival rate. We tested a new stable PGI2 analogue, beraprost sodium (Procyclin, Dornar) suitable for oral administration, in patients with primary and secondary pulmonary hypertension. A short-term study of cardiac catheterization in four patients with primary pulmonary hypertension showed a 15 +/- 12% reduction in mean pulmonary artery pressure in three of the four patients, and a 24 +/- 22% decrease in pulmonary vascular resistance in all four patients. Cardiac index increased by 27 +/- 14% in three of the four patients. Among three patients with secondary pulmonary hypertension, there was a 7% reduction in pulmonary artery pressure in one patient, and a 24 +/- 14% decrease in pulmonary vascular resistance in all three patients. In a long-term study (23 +/- 11 months), NYHA functional class improved from 3.0 +/- 0.7 to 2.4 +/- 0.5 in two of the five patients with primary pulmonary hypertension. Although the radiographic cardiothoracic ratio was not significantly improved, cardiac index increased by 78 +/- 60% in four of the five patients. Only two patients, one with primary and one with secondary pulmonary hypertension, died during the long-term follow-up period. Plasma TXB2/6-keto prostaglandin F1 alpha ratio decreased from 8.1 +/- 8.7 to 1.5 +/- 0.4. The optimal dose remains uncertain, but the initial dosage of 40-60 micrograms/day given in three to four doses for adult patients is considered to be acceptable. Side effects such as flushing face, headache, vomiting, and nausea were mild and resolved when the dose was reduced. Oral PGI2, beraprost, appears to be an effective and possibly adequate substitute for intravenous vasodilators in pulmonary hypertension for both short- and long-term management.
Saji
T
T
First Department of Pediatrics, Toho University School of Medicine, Tokyo.
Ozawa
Y
Y
Nakayama
T
T
Matsuura
H
H
Hashiguchi
R
R
Matsuo
N
N
Muto
H
H
Yamazaki
J
J
Morishita
T
T
Saito
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007223:Infant; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011652:Pulmonary Circulation / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; C048081:beraprost; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol