title: Modified-release sildenafil reduces Raynaud's phenomenon attack frequency in limited cutaneous systemic sclerosis.
abstract: OBJECTIVE
  To examine the effect of sildenafil in patients with Raynaud's phenomenon (RP) secondary to limited cutaneous systemic sclerosis (lcSSc).
  
  
  METHODS
  In this double-blind, placebo-controlled study, 57 patients with RP secondary to lcSSc were randomized to receive modified-release sildenafil 100 mg once daily for 3 days followed by modified-release sildenafil 200 mg once daily for 25 days or placebo. The primary assessment was the percentage change in the number of RP attacks per week in the per-protocol population. Secondary end points included Raynaud's Condition Score, duration of attacks, RP pain score, endothelial dysfunction assessed by a peripheral arterial tonometric (PAT) device, and serum biomarker levels.
  
  
  RESULTS
  The mean percentage reduction from baseline to day 28 in attacks per week was greater for modified-release sildenafil than for placebo (-44.0% versus -18.1%, P = 0.034); the mean number of attacks per week improved from 25.0 at baseline to 19.3 after placebo treatment and from 30.5 to 18.7 after modified-release sildenafil treatment (P = 0.244). Decreases from baseline in Raynaud's Condition Score, duration of attacks, and RP pain score were not significantly different between groups. Mean values and changes from baseline in PAT responses and serum biomarker levels were similar between groups. The most frequent adverse events were headache and dyspepsia; the majority of adverse events were mild or moderate.
  
  
  CONCLUSIONS
  Our findings indicate that modified-release sildenafil reduced attack frequency in patients with RP secondary to lcSSc and was well tolerated. Modified-release sildenafil may be a treatment option in this patient population.
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, Salford Royal Hospital, Salford, UK. ariane.herrick@manchester.ac.uk
authors.forename: Ariane L
authors.initials: AL
authors.lastname: Herrick
authors.forename: Frank
authors.initials: F
authors.lastname: van den Hoogen
authors.forename: Armando
authors.initials: A
authors.lastname: Gabrielli
authors.forename: Nihad
authors.initials: N
authors.lastname: Tamimi
authors.forename: Carol
authors.initials: C
authors.lastname: Reid
authors.forename: Damian
authors.initials: D
authors.lastname: O'Connell
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Vázquez-Abad
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects; D011928:Raynaud Disease / Q000188:drug therapy* / Q000209:etiology*; D045745:Scleroderma, Limited / Q000150:complications*; D055502:Secondary Prevention; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D015415:Biomarkers; D003692:Delayed-Action Preparations; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate