The review included 11 RCTs (n=2,131).
All 11 studies were rated as being of moderate quality, with scores ranging from 54 to 66.
Cilostazol (6 RCTs, 1,352 participants).
Effectiveness: at the end of the treatment period (ranging from 12 to 24 weeks), cilostazol had a significantly greater effect than placebo on both the MWD (WMD +52.19 m, 95% CI: 32.08, 72.31; 5 RCTs) and PFWD (WMD +39.75 m, 95% CI: 23.39, 56.10; 3 RCTs). Similar smaller, but still statistically significant, effects were seen 4 weeks into treatment (3 RCTs). Only one RCT reported follow-up after the end of treatment. This trial found no significant effect of cilastazol over placebo 6 weeks after active treatment ceased.
Adverse events: the drop-out rate was significantly higher in the cilostazol group than in the placebo group (OR 1.98, 95% CI: 1.27, 3.07; 5 RCTs). The death rates were similar in the cilostazol and placebo groups (5 RCTs; 0.7% in each group), and there was no significant difference between the groups in the rate of serious adverse events (4 RCTs). Adverse effects that were more common in those taking cilostazol included headache, dizziness, palpitation, diarrhoea and abnormal stool.
Beraprost (2 RCTs, 505 participants).
Effectiveness: one RCT reported changes in MWD and PFWD after 12 weeks; these were not statistically significantly greater in the beraprost group than in the placebo group.
Adverse events: beraprost was associated with significantly more headaches (2 RCTs), flushes (1 RCT) and vasodilation (1 RCT).
PGE1 (3 RCTs, 274 participants).
Effectiveness: at the end of the treatment period (4 weeks in 2 RCTs, 8 weeks in the other), PGE1 had a significantly greater effect than placebo on both the MWD (WMD +100.27 m, 95% CI: 15.76, 184.78; 3 RCTs) and PFWD (WMD +55.73 m, 95% CI: 21.54, 89.92; 3 RCTs). The results were similar when the analysis was at 4 weeks. Two RCTs reported follow-up after the end of treatment (one after 12 weeks and the other after 8 weeks), but found no benefit of PGE1 over placebo for either MWD or PFWD.
Adverse events: no serious adverse events were reported (3 RCTs). There were no significant differences between PGE1 and placebo for reddening of infusion vein (1 RCT), hypotension (1 RCT), or diarrhoea or nausea (1 RCT).,