Beraprost therapy for pulmonary arterial hypertension.
OBJECTIVE
The purpose of this study was to assess the safety and efficacy of the oral prostacyclin analogue beraprost sodium during a 12-month double-blind, randomized, placebo-controlled trial in patients with pulmonary arterial hypertension (PAH).


BACKGROUND
Pulmonary arterial hypertension is a progressive disease that ultimately causes right heart failure and death. Despite the risks from its delivery system, continuous intravenous epoprostenol remains the most efficacious treatment currently available.


METHODS
A total of 116 patients with World Health Organization (WHO) functional class II or III primary pulmonary hypertension or PAH related to either collagen vascular diseases or congenital systemic to pulmonary shunts were enrolled. Patients were randomized to receive the maximal tolerated dose of beraprost sodium (median dose 120 microg four times a day) or placebo for 12 months. The primary end point was disease progression; i.e., death, transplantation, epoprostenol rescue, or >25% decrease in peak oxygen consumption (VO(2)). Secondary end points included exercise capacity assessed by 6-min walk test and peak VO(2), Borg dyspnea score, hemodynamics, symptoms of PAH, and quality of life.


RESULTS
Patients treated with beraprost exhibited less evidence of disease progression at six months (p = 0.002), but this effect was not evident at either shorter or longer follow-up intervals. Similarly, beraprost-treated patients had improved 6-min walk distance at 3 months by 22 m from baseline and at 6 months by 31 m (p = 0.010 and 0.016, respectively) compared with placebo, but not at either 9 or 12 months. Drug-related adverse events were common and were related to the disease and/or expected prostacyclin adverse events.


CONCLUSIONS
These data suggest that beneficial effects may occur during early phases of treatment with beraprost in WHO functional class II or III patients but that this effect attenuates with time.
Barst
Robyn J
RJ
Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. rjb3@columbia.edu
McGoon
Michael
M
McLaughlin
Vallerie
V
Tapson
Victor
V
Rich
Stuart
S
Rubin
Lewis
L
Wasserman
Karlman
K
Oudiz
Ronald
R
Shapiro
Shelley
S
Robbins
Ivan M
IM
Channick
Richard
R
Badesch
David
D
Rayburn
Barry K
BK
Flinchbaugh
Robin
R
Sigman
Jeff
J
Arneson
Carl
C
Jeffs
Roger
R
D000284:Administration, Oral; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D011464:Epoprostenol / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011788:Quality of Life; D012720:Severity of Illness Index; D013607:Tablets; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*
D013607:Tablets; D014665:Vasodilator Agents; C048081:beraprost; D011464:Epoprostenol