Background and aims: Bempedoic acid (BA) is a new oral first-in-class ATP-citrate lyase inhibitor, available in Italy since May 2023. In the CLEAR study program, BA has been associated with a 15 to 26% reduction in LDLc from baseline, respectively in patients with or without statin. In real-world studies, the entity of LDL reduction was about 30-35%. The drug showed good tolerability and a safe profile, except for an increase in uric acid, gout events and serum creatinine. The aim of this study is to evaluate the effects of treatment with BA in high or very-high cardiovascular risk patients with diabetes mellitus in a real-world setting. Methods: Patients with diabetes mellitus and high or very high cardiovascular risk, who had LDLc levels above the recommended target despite maximally tolerated lipid-lowering therapy were recruited. We collected data about serum lipid profile, creatinine, and uric acid at baseline and after 3 months of therapy with BA. Results: We included 47 patients (median age 67.8±8.8 years, 22 female) of whom 31 (66.0%) were statin intolerant. The mean levels of LDLc decreased from the mean baseline value of 118.1±40.1 mg/dL to 79.7±28.7 mg/dl, showing a reduction of 38.4 mg/dl (32.5%) at follow-up (p<0.01). Among those who completed treatment, 27.7% achieved the recommended LDLc target. The magnitude of the LDLc reduction appeared to be quite different between statin-treated and statin-intolerant patients: the former showed an LDLc decrease of 25.5%, the latter a reduction of 35.0%. We found a statistically significant reduction in total cholesterol (-21.1%), non-HDL cholesterol (32.3%) and triglycerides (5.3%) levels, whereas HDL-C remained essentially unchanged. Five patients (10.6%) discontinued treatment because of adverse events, that were mild in severity. Four individuals (8.5%) required to begin treatment with urate-lowering medication due to a significant increase in uric acid. We found a non-significant increase in serum creatinine levels. Conclusions: in this study, the proportion of LDLc decrease was superior compared to results in RCTs, but similar to other findings in real-life studies. Interestingly, the reduction seemed more relevant in patients not treated with statins. This work confirms BA as a valid option for patients with diabetes at high or very high cardiovascular risk.
