Effects of cilostazol on the prognosis of lower extremity peripheral arterial disease in patients with diabetes mellitus in Korea: A nationwide population-based study

Abstract

Background Cilostazol increases pain-free walking distance in patients with lower extremity peripheral arterial disease (PAD). However, the effect of cilostazol on the prognosis of PAD in patients with diabetes remains unclear. We analyzed its effects on the long-term prognosis of Korean patients with diabetes and lower extremity PAD. Methods Data of patients with diabetes and lower extremity PAD between 2009 and 2018 were collected from the Korean National Health Information Database. The primary outcome was all-cause mortality from baseline to death or until December 31, 2022. The secondary outcomes were major adverse cardiac and cerebrovascular events (MACCE) and recurrent major adverse limb events (MALEs). Multiple Cox proportional hazard regression analyses were performed. Results We enrolled 14,768 patients with diabetes before PAD diagnosis with complete health screening data within 2 years of PAD diagnosis (5382 patients receiving cilostazol and 9386 controls). All-cause mortality was significantly lower in patients treated with cilostazol than in the controls. Antiplatelet treatment significantly lowered the risk of all-cause mortality compared to untreated controls, although the risk reduction did not differ significantly between antiplatelet agents. However, cilostazol administration did not reduce the risk of MACCEs. Treatment with cilostazol alone or in combination with antiplatelet agents was associated with a significant reduction in recurrent MALEs, without increasing the risk of major bleeding. Conclusions In patients with diabetes and lower extremity PAD, cilostazol may improve the prognosis without increasing the risk of bleeding. These findings provide epidemiological evidence for better PAD outcomes in patients with diabetes, although further research is required to elucidate the underlying mechanisms.