Platelet Inhibitors May Lower Risk of Digital Ulcers, Study Suggests

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Platelet inhibitors, or anti-platelet medication, is associated with a lower occurrence of digital ulcers — open sores on the fingers or toes — in people with systemic sclerosis (SSc), a study shows.

These findings may “assist rheumatologists in decision making regarding the use of platelet inhibitors in SSc patients with digital ulcers,” Alexandru Garaiman, the study’s first author and a doctoral student in Switzerland at the University Hospital Zurich’s rheumatology department, said in a press release.

However, platelet inhibitors’ potential benefits regarding digital ulcers should be confirmed in an appropriately controlled clinical trial “before any new treatment recommendations are made,” Garaiman added. Should these be confirmed, “this would mean we have another treatment option for SSc patients with digital ulcers, and one that is readily available in most countries at a low price.”

The results will be presented in a poster at the American College of Rheumatology’s virtual ACR Convergence 2021, running through Nov. 10.

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The poster is titled “Prediction of Digital Ulcers in Patients with Systemic Sclerosis Based on the Use of Platelet Inhibitors and Other Parameters – A EUSTAR Study on Derivation and Validation of a Clinical Prediction Model.”

SSc, also known as scleroderma, is characterized by blood vessel abnormalities, increased inflammation, and tissue scarring or fibrosis. Due to poor blood flow and narrowed blood vessels, about half of SSc patients develop digital ulcers, which can result in tissue death and amputation of the affected fingers or toes.

While “there has been significant progress in the treatment of digital ulcers” in recent years, “the complete prevention and healing of digital ulcers in patients with systemic sclerosis remains a big challenge in clinical practice,” Garaiman said.

“A plethora of vasoactive [blood vessel-targeting] and cardiovascular medications, including platelet inhibitors, are used in SSc patients in routine practice,” Garaiman added.

Platelets, tiny blood cells mainly known for their clotting-promoting role, are activated in SSc and thought to contribute to the disease’s characteristic blood vessel damage, inflammation, and fibrosis.

As such, it has been suggested that platelet inhibitors “might represent a therapeutic option in the management of DUs [digital ulcers],” the researchers wrote.

However, no clinical trial has evaluated the effects of anti-platelet medication in SSc-related digital ulcers.

To address this, Garaiman and colleagues set out to assess whether platelet inhibitors could reduce the occurrence of digital ulcers in SSc patients.

The team developed and validated a prediction model for digital ulcers using data from 3,710 SSc patients enrolled in the European Scleroderma Trials and Research (EUSTAR) registry.

Participants’ median age was around 57, and most were female (85.4%) and had limited SSc (67.8%). They had been living with the disease for a median of nearly nine years.

At study’s start (baseline), 486 (13.1%) patients showed digital ulcers and 150 (4%) were exposed to platelet inhibitors. At follow-up visits about a year later (median follow-up time, 1.03 years), 487 patients had digital ulcers and 90 remained on platelet inhibitors.

The predictive model included several factors that could potentially predict digital ulcers in SSc patients, including smoking, sex, pulmonary arterial hypertension, shortness of breath, disease duration, and use of a variety of medications, including platelet inhibitors.

The model was first tested in 2,827 patients who had their last follow-up visit before Jan. 1, 2017, and then validated in the 883 patients whose last recorded visit was after that date.

Results showed that, in both groups of patients, the model could accurately predict which patients had digital ulcers at the follow-up visit.

In addition, having digital ulcers at first visit was the greatest predictor of these wounds at the next follow-up visit, while the use of platelet inhibitors was associated with a lower likelihood of having digital ulcers at the next visit.

Particularly, patients with previous digital ulcers were six times more likely to show these wounds at the next visit, while those on anti-platelet medication were 75% less likely to have them.

“Our model shows good discrimination and adequate calibration for the difficult task of predicting the occurrence of DUs at a one-year follow up visit,” the researchers wrote, adding that “use of platelet inhibitors was among the factors predicting lower probability of DUs occurrence at follow-up.”