Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin I2 analogue: a double-blinded, randomized, controlled trial.
OBJECTIVE
In the current study, we hypothesized that beraprost would: 1) improve treadmill exercise performance and quality of life; and 2) decrease rates of ischemic events in patients with intermittent claudication.


BACKGROUND
Previous trials with beraprost sodium, an orally active prostaglandin I(2) analogue, in the treatment of claudication in patients with peripheral arterial disease (PAD) have been inconsistent.


METHODS
Patients with intermittent claudication (n = 897) were randomized to receive either 40 microg three times a day of beraprost with meals (n = 385) or placebo (n = 377) in a double-blinded manner for one year. The primary efficacy parameter was treadmill-measured maximum walking distance, as assessed at three and six months after randomization. Secondary efficacy parameters included treadmill-measured pain-free walking distance and change in quality of life.


RESULTS
There was no significant improvement in maximum walking distance in the beraprost group (16.7%) as compared with the placebo group (14.6%, p = NS). Administration of beraprost did not improve the pain-free walking distance (p = NS between treatment groups), and there was no improvement in the quality-of-life measures between the treatment groups. The incidence of critical cardiovascular events was 7.3% in the beraprost group and 11.4% in the placebo group (p = NS). There was a significant reduction in the combination of cardiovascular death and myocardial infarction in the beraprost group (p = 0.01).


CONCLUSIONS
Despite previous investigations suggesting efficacy, these results indicate that beraprost is not an effective treatment to improve symptoms of intermittent claudication in patients with PAD. The potential benefit of beraprost on critical cardiovascular events would require confirmation in a larger prospective investigation.
Mohler
Emile R
ER
University of Pennsylvania School of Medicine, Philadelphia Heart Institute, Room 432, 51 North 39th Street, Philadelphia, PA 19104, USA. mohlere@uphs.upenn.edu
Hiatt
William R
WR
Olin
Jeffrey W
JW
Wade
Michael
M
Jeffs
Roger
R
Hirsch
Alan T
AT
D000284:Administration, Oral; D000368:Aged; D004311:Double-Blind Method; D011464:Epoprostenol / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010146:Pain; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016138:Walking
D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; C048081:beraprost; D011464:Epoprostenol