A randomized trial of iloprost in patients with intermittent claudication

Abstract

Prostanoids, which promote vasodilation and reduce platelet aggregation, have been proposed as candidate therapies for intermittent claudication due to peripheral arterial disease (PAD). However, studies of these medications have yielded inconsistent results. This study tested the hypothesis that iloprost, an oral prostacyclin analogue, would improve walking distance and quality of life in patients with intermittent claudication. The study was a multi-center, randomized, double-blind, placebo-controlled trial comparing three doses of oral iloprost (50 μg, 100 μg, or 150 μg twice daily), pentoxifylline, or placebo in 430 patients with intermittent claudication. The primary outcome measure was improvement in absolute claudication distance (ACD) after 6 months. Secondary outcomes included initial claudication distance and quality of life assessment. Placebo increased ACD by 3.3%, and iloprost increased peak ACD by 7.7%, 8.8% and 11.2% at the 50 μg, 100 μg, and 150 μg twicedaily doses, respectively (all insignificant relative to placebo). Pentoxifylline increased ACD by 13.9% relative to placebo (p = 0.039). Neither iloprost nor pentoxifylline enhanced quality of life. These results indicate that oral iloprost is not effective in improving exercise performance or quality of life in patients with PAD who have intermittent claudication.

Pharmacological Treatment and Current Management of Peripheral Artery Disease

“…117 Although pentoxifylline has been shown to improve symptoms of claudication, the overall benefit is small. 118 Accordingly, pentoxifylline is considered for therapy only in patients who are not able to receive or tolerate cilostazol. 16 …”

A systematic review and economic evaluation of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease.

“…Of the eight trials 34,58,70,71,73,76,77 comparing pentoxifylline versus placebo in terms of MWD, two trials significantly favoured pentoxifylline over placebo: Creager et al (p = 0.039) 70 and Di Perri et al (p < 0.01). 77 Of these, the Di Perri 77 trial did not use a treadmill protocol, instead measuring the distance that a patient could walk on a horizontal level at metronome controlled speed of 120 steps per minute, with a follow-up at 8 weeks.…”

“…77 Of these, the Di Perri 77 trial did not use a treadmill protocol, instead measuring the distance that a patient could walk on a horizontal level at metronome controlled speed of 120 steps per minute, with a follow-up at 8 weeks. The Creager et al 70 trial used a graded treadmill test protocol, and found a significant effect on MWD at 24 weeks. Of the six trials finding no significant difference between groups for MWD, one of these used the graded test (Dawson et al; 58 p = 0.82) and had a follow-up of 24 weeks.…”

“…Of these, the Gallus et al 76 study had a follow-up of only 8 weeks [ratio of percentage change from baseline 1.05 (95% CI 0.81 to 1.36), which was non-significant], and the other studies had follow-up of 24 weeks: Lindgarde et al 71 (p = 0.09), Porter et al 73 (two-sided p = 0.32), Otsuka 21-98-213 34 (p = 0.24) and Otsuka 21-94-301 34 (p = 0.29). The pentoxifyllineversus-placebo comparison trials that reported significant treatment effect for MWD generally also reported significant treatment effect for PFWD (see Chapter 5, Pain-free walking distance) and vice versa; however, there were a couple of exceptions in that the Creager et al 70 trial, which found a significant treatment effect for MWD, did not find a significant treatment effect for PFWD, and the Dawson et al 58 trial did not find an effect for MWD but did find a treatment effect for PFWD (see Chapter 5, Pain-free walking distance).…”

“…Of the seven trials comparing pentoxifylline 1200 mg versus placebo in terms of PFWD, five found no significant difference between treatment groups (Creager et al, 70 Lindgarde et al, 71 Gallus et al 76 and Otsuka 21-98-213, 21-94-301 34 ), whereas two significantly favoured pentoxifylline over placebo for PFWD (Dawson et al 58 and Porter et al…”