Purpose of Review The aim of creating an orally active non-statin cholesterol-lowering drug was achieved with bempedoic acid, a small linear molecule providing both a significant low-density lipoprotein cholesterol (LDL-C) reduction and an anti-inflammatory effect by decreasing high-sensitivity C-reactive protein. Bempedoic acid antagonizes ATP citrate-lyase, a cytosolic enzyme upstream of HMGCoA reductase which is the rate-limiting step of cholesterol biosynthesis. Bempedoic acid is a pro-drug converted to its active metabolite by very-long-chain acyl-CoA synthetase 1 which is present mostly in the liver and absent in skeletal muscles. This limits the risk of myalgia and myopathy. The remit of this review is to give clinical insights on the safety and efficacy of bempedoic acid and to understand for whom it should be prescribed. Recent Findings Bempedoic acid with a single daily dose (180 mg) reduces LDL-C by a mean 24.5% when given alone, by 18% when given on top of a major statin and by 38–40% when given in a fixed-dose combination with ezetimibe. Bempedoic acid does not lead to the risk of new-onset diabetes, and moderately improves the glycaemic profile. Summary The extensive knowledge on bempedoic acid mechanism, metabolism and side effects has led to an improved understanding of the potential benefits of this agent and offers a possible alternative to cardiologists and clinical practitioners somewhat worn out today by the occurrence of the muscular side effects of statins.

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Background. Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality, being twofold to fourfold more common in patients with type 2 diabetes mellitus (T2DM) than in individuals without diabetes. However, despite this decade-old knowledge, particularly challenging remains the identification of a specific prognostic risk biomarker. Methods. Taking advantage of a large sample of Caucasian patients (n = 568) with a diagnosis of T2DM followed for a median of 16.8 years, the present study was aimed at testing the hypothesis that fasting serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels could be prognostic for major cardiovascular events (MACE) and all-cause mortality. Results. Median levels of PCSK9 were 259.8 ng/mL, being higher in women compared to men and increasing even more in the presence of a complication (e.g., diabetic kidney disease). PCSK9 positively correlated with markers of blood glucose homeostasis (e.g., HbA1c, fasting insulin and HOMA-IR) and the atherogenic lipid profile (e.g., non-HDL-C, apoB and remnant cholesterol). Serum PCSK9 predicted new-onset of MACE, either fatal or non-fatal, only in women (Odd Ratio: 2.26, 95% CI 1.12–4.58) and all-cause mortality only in men (Hazard Ratio: 1.79 [1.13–2.82]). Conclusions. Considering that up to two-thirds of individuals with T2DM develop ASCVD in their lifetime, the assessment of circulating PCSK9 levels can be envisioned within the context of a biomarker-based strategy of risk stratification. However, the sex difference we found highlight an urgent need to develop sex-specific risk assessment strategies. Trial registration It is a retrospective study