Bempedoic Acid and Statins in Lipid-Lowering Strategy: Which Came First, the Egg or the Chicken?

Abstract

The goal in cardiovascular prevention is the reduction of morbidity and mortality through the promotion of healthy lifestyles in the general population. The management of modifiable risk factors with pharmacological and non-pharmacological interventions, based on the individual risk is the first strategy suggested by the current guidelines. Several epidemiological studies have clearly shown the direct correlation between high levels of low-density lipoprotein cholesterol (LDL-C) and incidence of cardiovascular diseases. On the other hand, numerous randomized clinical studies have reported a huge benefit in terms of major cardiovascular events achievable by the reduction of LDL-C, thus supporting the notion that “the lower is better”. Among the lipid-lowering strategies, statins are the drugs of choice in cardiovascular prevention, at both primary and secondary level. To achieve the ambitious targets suggested by the current guidelines, other lipid-lowering therapies are currently available in addition to statins, such as ezetimibe the inhibitors of the PCSK9. Pharmacological research has recently led to the development of a new drug, the bempedoic acid, which further enrich the available therapies. This drug also acts on the biosynthesis of cholesterol but at upstream level than statins. From the biochemical point of view, it has the potential to be considered before the statin with consequent titration of statins to achieve the desirable LDL-C target. In the present review, the biochemical and pharmacological characteristics of bempedoic acid are discussed. An overview of the clinical data that support its use in the management of the cardiovascular patient and its allocation in the lipid-lowering scenario will be also provided.

Evolving Concepts of the SCORE System: Subtracting Cholesterol from Risk Estimation: A Way for a Healthy Longevity?

“…Alongside traditional lipid-lowering therapies (LLT), several new drugs have been approved by the FDA for the treatment of dyslipidemias, and a growing number of studies are underway to evaluate their efficacy and safety profiles. Bempedoic acid, the first inhibitor of the ATP citrate lyase class, represents a new lipid-lowering drug that fits into our therapeutic armamentarium [ 36 ]. The CLEAR Outcomes study [ 37 ] was the first to evaluate the efficacy of bempedoic acid in primary prevention in statin-intolerant patients.…”

“…The new therapeutic options currently available aim to improve therapeutic adherence and reach target LDL-C levels more easily. Among these, in addition to ezetimibe and/or bempedoic acid, which are able to reduce LDL-C levels by 18% [ 69 ] and 24% [ 36 ], respectively, an important role is now played by PCSK 9 inhibition through monoclonal antibodies (alirocumab and evolocumab) [ 70 ] and siRNA (inclisiran) [ 39 , 71 ]. Blocking the PCSK9 protein results in increased recirculation of the LDL-C receptor on the cell surface, thus improving its function [ 70 ].…”

2023: The Best Year Ever for Future Pharmacology (and Even Better Years to Come)

“…I am also pleased to let you know that, over the last 12 months, the three papers that attracted the most views were those by Marques and Vale (2023), with some 4719 views at the time of writing [2]; by Thong et al (2023), with some 3900 views [3]; and by Natale et al (2023), with 3579 views [4]. Well done to our colleague scientists!…”