Combining dipyridamole and cilostazol with up‐dosing antihistamines improves outcomes in chronic spontaneous urticaria with high D‐dimer levels: A randomized controlled trial

Abstract In a double‐blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up‐dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D‐dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D‐dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group ( p = 0.046). D‐dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up‐dosing antihistamines may be more effective for CSU patients with high D‐dimer levels compared to up‐dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D‐dimer levels observed in the antiplatelet group.