Clopidogrel treatment may associate with worsening of endothelial function and development of new digital ulcers in patients with systemic sclerosis: results from an open label, proof of concept study

BMC Musculoskeletal Disorders

Research Article

Vasileios Gkizas¹  Periclis Davlouros¹  Dimitrios Alexopoulos¹  Konstantinos Ntelis²  Alexandra Filippopoulou²  Dimitrios Daoussis²  Andrew P. Andonopoulos² 

[1] Department of Cardiology, Patras University Hospital, University of Patras Medical School, Rion, 26504, Patras, Greece;Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Rion, 26504, Patras, Greece;

关键词: Systemic sclerosis;    Scleroderma;    Clopidogrel;    Digital ulcers;    Platelets;   

DOI  :  10.1186/s12891-016-1072-1

 received in 2015-12-11, accepted in 2016-05-11,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundActivated platelets release serotonin that binds 5-HT2B receptor on fibroblasts leading to fibroblast activation. Clopidogrel, an inhibitor of ADP-dependent platelet activation prevents fibrosis in animal models of systemic sclerosis (SSc). We aimed at assessing whether i) ADP-dependent platelet activation is increased in patients with SSc compared to healthy subjects and patients with rheumatoid arthritis (RA) and ii) whether clopidogrel can effectively suppress ADP-dependent activation, reduce circulating serotonin levels and hence, favorably affect fibrosis or vasculopathy in patients with systemic sclerosis.MethodsThirteen patients with SSc were recruited. Platelet activation was assessed by aggregometry prior to and following 14 days of clopidogrel treatment. At the same time points serotonin and soluble vascular cell adhesion molecule 1 (s-VCAM1), a marker of endothelial dysfunction, were measured.ResultsADP-dependent platelet activation was similar between patients with SSc (n = 13), patients with RA (n = 28) and healthy subjects (n = 22) (mean ± SEM AU*min: 392.1 ± 58.4, 535.5 ± 61.33 and 570.9 ± 42.9 in patients with SSc, patients with RA and healthy subjects respectively, p = 0.14). Clopidogrel treatment significantly reduced platelet activation in patients with SSc (mean ± SEM AU*min: 392.1 ± 58.4 vs 163.8 ± 51.7, p = 0.014). Clopidogrel treatment did not affect serotonin levels but led to a significant increase in s-VCAM1 (p = 0.03). Three patients developed new digital ulcers during the study. The potential association of the study drug with the development of new digital ulcers led to early termination of the study.ConclusionClopidogrel may worsen markers of endothelial function and associate with development of new digital ulcers in patients with SSc.Clinical trial registrationISRCTN63206606. Registered 02/Dec/2014.

【 授权许可】

CC BY   
© Ntelis et al. 2016