Background: Systemic sclerosis (SSc) is characterized by fibrosis and widespread vascular pathology. The initial events involve endothelial cell damage,loss of normal vasodilatory mediators and excessive vasoconstriction. The most evident manifestation of the vascular involvement is Raynaud's phenomenon(RP)and digital ulceration. Digital ulceration remains a serious complication and effective therapy remains elusive. Statins display pleiotropic effects including effects on endothelial function that may be of benefit in retarding vascular injury.
Objectives: To evaluate the potential efficacy of statin therapy in the amelioration of endothelial dysfunction and in the management of RP and DU.
Methods: Forty SSc patients (37 females and 3 males), mean age 49.7 years and mean disease duration of 6.5 years who had experienced RP for a mean of 8.0 years were studied from Nov 2005-March 2006.All patients fulfilled the ACR criteria for the classification of SSc with RP secondary to SSc despite ongoing vasodilator therapy. None were on ERA. Exclusion criteria included diabetes, hypercholesterolemia, hypertension, cardiac, hepatic and renal diseases. Patients were randomized into 2 groups; the first group(n=20)received 40mg/day of atorvastatin for 4 months and the second group(n=20)received placebo. The patients were matched for age, sex, SSc classification and concomitant medications. Assessment of DU was performed monthly. Outcome measures were the number of DU and new ulcer appearance. Secondary endpoints included the modified Scleroderma Health Assessment Questionnaire Disability Index(SHAQ-DI),safety and tolerability. Serial monthly liver and renal monitoring was done. Measurement of functional status in relation to RP included the SHAQ-DI,visual analogue scale(VAS)for RP,DU and pain scales and VAS for physician's global assessment for health.The level of markers of endothelial damage,sE-Selectin,ICAM-1,thrombomodulin,vWF, malonylaldehyde,lipid peroxide,ESR,hsCRP,endothelin-1 and nitric oxide were assessed using specific ELISA assay kits at baseline and after 4 months of therapy.
Results: Fifty-nine percent of patients in the statin group and 50%of those in the placebo group had DU at entry. The mean number of ulcers at entry was similar in both groups. Scores for physician and patient assessment of RP and ulcer severity and ulcer pain at baseline were similar in the statin and placebo groups.The SHAQ-DI was also similar in both groups at baseline. The overall number of DU was significantly reduced in the statin group(p< 0.05). Among patients in the statin group a mean of 1.6 new ulcers per patient developed compared to 2.5 new ulcers per patient in the placebo group(p= 0.003).There was a statistically significant improvement in SHAQ-DI score in patients receiving statin compared to those on placebo(p< 0.001).VAS for RP,DU and pain scales as well as the VAS for physician global assessment of health improved significantly in the statin group compared to the placebo group. The drug was well tolerated and there were no drop-outs. Endothelial markers of activation showed statistically significant improvement from baseline values in the statin versus the placebo group.

Conclusion: The results of this study suggest that statins ameliorate vascular dysfunction and improve patient function. The good patient tolerance,their safety and relative inexpensiveness may prove statins invaluable in maintaining vascular integrity and a potentially welcome addition to the limited therapeutic arsenal for SSc.