Levien Patients Sildenafil 20 patients 16 secondary RP 2 primary RP 20 patients primary RP 19 patients secondary RP 10 patients secondary RP Tadalafil 25 patients secondary RP 39 patients secondary RP 14 patients secondary RP 12 patients secondary RP Vardenafil 40 patients 33 secondary RP 7 primary RP Randomized double-blind crossover placebo-controlled Randomized double-blind crossover Placebo-controlled Open-label Open-label Randomized double-blind cross-over Randomized double-blind placebo-controlled cross-over Active-controlled Open-label Open-label Sildenafil 50 mg twice daily × 4 weeks Sildenafil 50 mg twice daily × 2 weeks Sildenafil 25 to 150 mg/day for up to 6 months Sildenafil 25 mg 3 time s daily × 6 weeks initiated following 5 days of iV iloprost therapy Tadalafil 20 mg or placebo every other day × 6 weeks Tadalafil 20 mg daily × 4 weeks Tadalafil 20 mg 2 to 3 times per week × 4 weeks (9 patients) or pentoxifylline 600 mg twice daily × 4 weeks (5 patients) Tadalafil 10 or 20 mg every other day × 6 weeks Vardenafil 10 mg twice daily × 2 weeks Frequency and duration reduced RCS improved No difference between sildenafil and placebo in blood flow, disability, pain, or RCS Mean number of ulcers reduced VAS scores for RP, pain, and activity were improved Symptomatic improvement and ulcer healing in approximately half Frequency and duration reduced Mean daily RCS improved More ulcers healed during tadalafil Fewer new finger tip ulcers developed during tadalafil Improvements with tadalafil on Patient Global Assessment, Physician Global Assessment, and impact on daily living on SSc HAQ No significant differences from placebo in RCS 60 or RP frequency or duration RCS improved with tadalafil compared with pentoxifylline Attack frequency and duration reduced with tadalafil Ulcer healing observed RCS reduced Dovepress References 65,66 5 58 61 59 57 62 63 Table 3 Summary of phosphodiesterase type 5 inhibitor clinical trials on Raynaud’s phenomenon (RP) with clinical endpoints Study design Treatment Outcomes Abbreviations and notes: RCS, Raynaud’s Condition Score (patient assessment of the extent to which they felt handicapped by Raynaud attacks daily based on frequency, total daily duration, and severity of attacks using a 10-point scale; 0 points, subject felt not handicapped by Raynaud attacks; 10 points, subject felt extremely handicapped); HAQ, Health Assessment Questionnaire. 19 patients with systemic scleroderma, severe Raynaud, and digital ulcers.65,66 Another open-label study assessed tadalafil in 12 patients with secondary Raynaud and painful digital ulcers or finger tip necrosis at baseline. The mean time to ulcer healing was 5 weeks and the mean time to healing of fingertip necrosis was 8 weeks.62 In addition to open-label studies, several case reports and case series describing the use of PDE5 inhibitors in patients primarily with secondary RP have reported symptomatic improvement, ulcer healing, and objective improvements in blood flow.4,67–80 Tadalafil has been compared with pentoxifylline in the treatment of RP in a study enrolling 14 male patients with severe Raynaud associated with autoimmune diseases. RCS demonstrated greater improvement in the tadalafil treated patients. Attack frequency declined 59% with tadalafil treat- ment compared with 36% reduction with pentoxifylline. Attack duration was also significantly reduced with tadalafil therapy compared with pentoxifylline. Both physician and patient assessments of RP were also improved after 4 weeks of therapy with tadalafil (P  0.05 compared with 2 weeks 172 submit your manuscript | www.dovepress.com Dovepress Vascular Health and Risk Management 2010:6