Effect of Atorvastatin on vascular endothelial function in early Systemic Sclerosis: An open label Randomized Controlled trial

Background/Aims Systemic Sclerosis (SSc) is driven by early endothelial dysfunction, leading to loss of endothelium-dependent vasodilatation. This predisposes to increased stiffness of large arteries. Prospective studies have found a conflicting role of statins in improving vascular function in established SSc. We undertook this study to explore if statins influence endothelium dependent vasodilation in early SSc Methods In this single center open label randomized controlled trial between July 2021 to January 2022, SSc patients (ACR-EULAR 2013) between 18-65 years, with duration < 3 years from the first non-Raynaud's symptom were included. Those with complicated Raynaud's, overlap syndromes and cardiovascular comorbidities were excluded. Participants were randomized into statin (atorvastatin 40 mg/day/A40) or no -statin arm. Both groups received stable doses of immunosuppression, during the study period. The primary outcome of flow-mediated dilation (FMD %) of brachial artery, measured by single assessor and secondary outcomes of common carotid intima medial thickness (CIMT), modified Rodnan Skin score (mRSS), Raynaud's visual analogue scale (RayVAS:0-10), hs CRP, von Willebrand factor and oxidized low-density lipoproteins were measured at baseline and 16 weeks. All patients provided written informed consent; study protocol was approved by IEC(JIP/IEC/2020/026). Considering a change in FMD of 1% between arms as clinically meaningful, sample size was calculated to be 144. Analysis was performed using SPSS v.19.CTRI registration no: REF/2020/07/03495 Results Total 71 eligible patients were randomized into statin(n = 36) and no-statin(n = 35) arms. Baseline parameters were comparable between arms. Baseline mRSS was 14.25. On per-protocol analysis of statin (n = 28) and no-statin (n = 32) arms, there was no significant difference in FMD either at baseline or at 16 weeks (table 1). At week 16, basal brachial artery diameter increased (p = 0.008) in statin arm. Ray VAS scores improved in the statin arm,not achieving significance(p = 0.15). An increase in mRSS from 14 to 16 was noted in no-statin arm , whereas it remained stable in the statin arm (14.5). Secondary endpoints were not met. No adverse events were noted. Conclusion In early SSc, atorvastatin 40 mg/day, added to background immunosuppression, failed to improve endothelial function, assessed using brachial FMD, at 16 weeks. Stabilization of skin tightening was noted in the statin arm. Disclosure A.C. Das: None. M.M. Thabah: None. C. Mariaselvam: None. R. Vijayan: None. A. Anantharaj: None. V. Negi: None.