Patients with metabolic dysfunction–associated steatotic liver disease have preserved in vitro responses to antiplatelet drugs

Background: Patients with metabolic dysfunction–associated steatotic liver disease (MASLD) are at a risk of developing cardiovascular disease. Antiplatelet therapy not only prevents cardiovascular disease in these patients, but may also lower the risk of progression into advanced stages of fibrosis. However, patients with MASLD-associated cirrhosis often have complex changes in the hemostatic system and have been excluded from randomized trials.

Objectives: The aim of this study was to assess the potency of antiplatelet drugs in these patients with MASLD-associated cirrhosis.

Methods: We included patients with MASLD-associated cirrhosis (n = 19), patients with type 2 diabetes (DM2) and steatosis (n = 22), patients with steatosis only (n = 15), and healthy controls (n = 20). We measured basal platelet aggregation and activation using light transmission aggregometry and flow cytometry. We subsequently measured platelet aggregation and activation after in vitro addition of aspirin, cangrelor, and ticagrelor and compared the antiplatelet response in patients and healthy controls.

Results: Rates of aspirin resistance as measured by light transmission aggregometry were similar between patients with MASLD-associated cirrhosis and healthy controls (21% vs 16%), but were significantly higher in patients with DM2 and steatosis (50% [P = .02] vs controls) and patients with steatosis only (53% [P = .05] vs controls). In patients with DM2 and steatosis, but not with MASLD-associated cirrhosis, the potency of cangrelor was significantly lower than that in healthy controls (P = .028).

Conclusion: The in vitro potency of aspirin, cangrelor, and ticagrelor in samples of patients with MASLD-associated cirrhosis is similar to that of healthy controls. In contrast, the potency of commonly used antiplatelet drugs may be altered in patients with DM2 and steatosis and in patients with steatosis only.