Clopidogrel Treatment in Scleroderma Patients Shown to Induce Digital Ulcers

Clopidogrel (Plavix) treatment may worsen blood vessel dysfunction and lead to the development of new digital ulcers in patients with scleroderma. The results of this proof-of-concept study indicated that platelet activation is not a main driver of fibrosis, also highlighting the need for caution when treating scleroderma patients who also suffer from heart disease.

The study “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,“ was published in the journal BMC Musculoskeletal Disorders.

Recent research has suggested that patients with scleroderma might have abnormal activation of their blood platelets, caused by the damage to blood vessels that characterize the disease. Several platelet-linked molecules are increased in the blood of patients, and an earlier study showed that the release of serotonin, caused by platelet activation, might induce skin fibrosis in experimental animals.

The data have led researchers to hypothesize that fibrosis is the result of a chain of events, starting with dysfunctional endothelial cells — forming the lining of blood vessels — over platelet activation, serotonin release and activation of fibrosis producing fibroblasts.

Clopidogrel is a drug blocking the activation of platelets, and is used in heart disease patients. Scientists from the University of Patras Medical School in Greece measured the levels of platelet activation in 13 patients with scleroderma and 22 healthy control individuals. In contrast to their theory, researchers found no difference in platelet activation between patients and controls.

The study also explored if clopidogrel could block platelet activation in scleroderma patients, reduce the levels of serotonin, and improve fibrosis and blood vessel dysfunction, according to the scientist’s theory. They were again surprised to find that the treatment did block platelets, but had no impact on serotonin levels.

Moreover, instead of improving fibrosis, clopidogrel treatment worsened endothelial cell dysfunction, as well as symptoms. Three patients, or 23 percent, who never had digital ulcers before, or who had not developed ulcers in a long time, now saw new ulcers on their hands. Other disease parameters, such as skin thickening, internal organ, including lung function and overall functional impairment were unaffected by the treatment.

Because of the issues observed, the study was stopped before reaching the planned two years of treatment. Most patients had been treated for 12 months when the study was discontinued. Furthermore, since many scleroderma patients suffer from simultaneous heart disease, the data showed that it  might be better to avoid clopidogrel as a treatment for heart-related health concerns.