Statins: potentially useful in therapy of systemic sclerosis-related Raynaud's phenomenon and digital ulcers.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by fibrosis and widespread vascular pathology. Raynaud's phenomenon (RP) and digital ulceration are prominent manifestations of vascular involvement in SSc. Digital ulcers (DU) remain a serious complication, and effective therapy remains elusive. Statins display pleiotropic effects on endothelial function that may potentially retard vascular injury. We evaluated the potential efficacy of statin therapy in endothelial dysfunction and in management of RP and DU.

METHODS: Eighty-four SSc patients who fulfilled the American College of Rheumatology criteria for classification of SSc with secondary RP despite ongoing vasodilator therapy were randomized into 2 groups; the first group (n = 56) received 40 mg/day atorvastatin for 4 months; the second group (n = 28) received placebo. Seventy-five healthy volunteers served as controls. Assessment of RP and DU was performed monthly. The primary outcome measure was the number of DU. Secondary endpoints included the modified Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI), safety, and tolerability. Measurement of functional status in relation to RP included the SHAQ-DI, visual analog scale (VAS) for RP, DU and pain scales, and VAS for physician's global assessment for health. Endothelial damage markers were also assessed. Endothelium-dependent flow-mediated dilatation was measured by high-resolution echo-Doppler ultrasonography.

RESULTS: The overall number of DU was significantly reduced in the statin group. Among patients in the statin group a mean of 1.6 new ulcers developed per patient compared to 2.5 new ulcers per patient in the placebo group. There was a statistically significant improvement in SHAQ-DI score in patients receiving statin versus those on placebo. VAS for RP, DU severity, and pain scales and the VAS for physician global assessment improved significantly in the statin group compared to the placebo group. Endothelial markers of activation showed statistically significant improvement from baseline values in the statin versus the placebo group.

CONCLUSION: Our results showed that statins retarded vascular injury and improved patient function. The findings suggest that statins may aid in treating RP and DU in SSc patients. Given the safety and relative low cost of statins and good patient tolerability to this class of drugs, statins may be of clinical benefit in SSc patients.