Table 1 Summary of intravenous iloprost clinical trials on Raynaud’s phenomenon (RP) Study design Randomized double-blind placebo-controlled Randomized double-blind placebo-controlled Randomized double-blind placebo-controlled crossover Randomized Double-blind placebo-controlled crossover Randomized double-blind placebo-controlled crossover Randomized double-blind Randomized single-blind Randomized double-blind double-dummy Active treatment iloprost 0.5–2 ng/kg/min iV infusion over 6 hours on 5 consecutive days iloprost 0.5–2 ng/kg/min over 6 h on 5 consecutive days iloprost 0.5–2 ng/kg/min over 6 h on 5 consecutive days iloprost 0.5–2 ng/kg/min over 6 h on 3 consecutive days Outcomes Frequency and severity reduced Physician’s rating of treatment effect improved No difference in digital ulcer healing Complete digital ulcer healing with iloprost No difference in frequency, duration, and severity Frequency reduced No differences in duration or severity Frequency and severity reduced No difference in duration iloprost 1–3 ng/kg/min over 5 hours on 3 consecutive days Frequency and severity decreased with iloprost iloprost 0.5 ng/kg/min or iloprost 2 ng/kg/min over 6 h on 3 consecutive days iloprost 2 ng/kg/min over 8 h on 5 consecutive days, then over 8 hrs on 1 day every 6 weeks or Nifedipine 40 mg/day Frequency, severity, duration, and digital skin lesions reduced to similar extent with low dose and high dose Skin scores reduced to greater extent with iloprost than nifedipine Severity scores reduced with iloprost, but not with nifedipine iloprost 0.5–2 ng/kg/min for Frequency, duration, severity, and 8 hours on 3 consecutive days, incidence of digital lesions reduced repeated at week 8 or Nifedipine 10 mg to comparable extent with iloprost 3 times daily × 4 weeks, then 20 mg 3 times and nifedipine daily × 12 weeks Levien Patients 131 patients secondary RP 35 patients secondary RP 13 patients secondary RP 29 patients 26 secondary RP 3 primary RP 12 patients secondary RP 55 patients secondary RP 46 patients secondary RP 23 patients secondary RP approved for the prevention of new digital ulcers in patients with systemic sclerosis and digital ulcers. Approval was based on the results of two studies (Table 2). One randomized, double-blind, placebo-controlled study enrolling 122 patients with systemic sclerosis assessed the effects of bosentan in the prevention of digital ulcers. Patients received bosentan 62.5 mg twice daily for 4 weeks, then 125 mg twice daily for 12 weeks, or placebo for 16 weeks. Bosentan-treated patients had a 48% reduction in the mean number of new ulcers compared with those in the placebo group (1.4 vs 2.7 new ulcers; P = 0.0083). A similar percent- age of patients in both groups developed ulcers, and bosentan did not appear to delay development of the first digital ulcer. There was no difference between treatment groups in the healing of existing ulcers.42 In an open-label extension of this study, 88 patients (57 previously in the bosentan arm and 31 previously in the placebo arm) continued bosentan therapy for an additional 12 weeks. The mean number of new ulcers 170 submit your manuscript | www.dovepress.com Dovepress during follow-up was 0.7.43 In another similar study enrolling 188 patients with systemic sclerosis, bosentan 62.5 mg twice daily for 4 weeks and then 125 mg twice daily for 20 to 32 weeks was compared with placebo in the prevention and healing of digital ulcers. Total new ulcers during 24 weeks of follow-up were 1.9 on bosentan vs 2.7 on placebo (P = 0.035). Healing parameters, including time to healing of a selected cardinal ulcer, to to healing of all digital ulcers, and percent of patients with complete healing did not differ between treatment groups.44 Another study noted improvement in flow-mediated dilation with bosentan therapy in patients with systemic sclerosis, but did not include assessment of the frequency or severity of RP or digital ulcers.45 The use of bosentan in the treatment of digital ulcers in 26 patients with systemic sclerosis unresponsive to CCB, ARBs, and sildenafil has also been described. Bosentan 62.5 mg twice daily for the first month, then 125 mg twice daily for an additional 35 weeks was administered. Healing Vascular Health and Risk Management 2010:6 Dovepress References 20 23 24 22 21 25 28 27