Beyond statins: New pharmacological targets to decrease LDL-cholesterol and cardiovascular events

Raschi, Emanuel; Casula, Manuela; Cicero, A.F.G.; Corsini, Alberto; Borghi, Claudio; Catapano, Alberico L.

doi:10.1016/j.pharmthera.2023.108507

Cited by 23 publications

(12 citation statements)

References 171 publications

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“…Adverse effects of bempedoic acid included a higher incidence of gout, cholelithiasis and increases in serum creatinine, uric acid and liver enzyme levels [ 43 , 50 ]. The same study suggests that in patients intolerant of statins, treatment with bempedoic acid was associated with a lower risk of MACEs [ 50 , 51 , 52 ]. A meta-analysis associated treatment with bempedoic acid with a reduction in cardiovascular risk, new-onset diabetes and worsening diabetes [ 51 , 53 ].…”

Section: Present Therapeutic Optionsmentioning

confidence: 98%

“…The same study suggests that in patients intolerant of statins, treatment with bempedoic acid was associated with a lower risk of MACEs [ 50 , 51 , 52 ]. A meta-analysis associated treatment with bempedoic acid with a reduction in cardiovascular risk, new-onset diabetes and worsening diabetes [ 51 , 53 ]. Bempedoic acid could therefore be a useful adjunct in the treatment of lipid-lowering agents.…”

Section: Present Therapeutic Optionsmentioning

confidence: 98%

“…Based on the results of all these studies, a position paper was recently published recommending the use of bempedoic acid in atherosclerotic CVD, familial hypercholesterolaemia and statin intolerance. The authors of this paper also points out that while there is not yet sufficient data to support the role of bempedoic acid in the primary prevention of CVD, its beneficial effects on plasma glucose and inflammatory markers suggest that this drug may be a rational choice in patient-centred care for certain primary prevention groups [ 50 , 51 , 54 ]. Currently, bempedoic acid is used as either a monotherapy in patients with well-documented statin intolerance or as a part of FDC medication together with statins or other lipid-lowering medications.…”

Section: Present Therapeutic Optionsmentioning

confidence: 99%

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Present and Future of Dyslipidaemia Treatment—A Review

Merćep,

Vujević,

Strikić

et al. 2023

JCM

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One of the greatest burdens on the healthcare systems of modern civilization is cardiovascular diseases (CVDs). Therefore, the medical community is looking for ways to reduce the incidence of CVDs. Simple lifestyle changes from an unhealthy to a healthy lifestyle are the cornerstone of prevention, but other risk factors for cardiovascular disease are also being currently targeted, most notably dyslipidaemia. It is well known that lowering serum lipid levels, and in particular lowering elevated LDL-cholesterol, leads to a reduction in major cardiovascular events. Although the focus to date has been on LDL-cholesterol levels and lowering them with statin therapy, this is often not enough because of increased concentrations of other lipoprotein particles in the serum and residual cardiovascular risk. Since lowering LDL-cholesterol levels is successful in most cases, there has been a recent focus on lowering residual cardiovascular risk. In recent years, new therapeutic options have emerged that target triglyceride-rich lipoproteins, lipoprotein (a) and apolipoproteins C and B. The effects of these drugs on serious adverse cardiovascular events are not yet known, but recent studies with some of these drugs have shown significant results in lowering total lipid levels. The aim of this review is to present the current therapeutic options for the treatment of dyslipidaemia and to describe the newly approved drugs as well as the drugs that are still in development. Although at this stage we cannot say with certainty whether these agents will be approved and widely used, it is safe to say that our views on the treatment of dyslipidaemia are certainly changing.

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Section: Present Therapeutic Optionsmentioning

confidence: 98%

Section: Present Therapeutic Optionsmentioning

confidence: 98%

Section: Present Therapeutic Optionsmentioning

confidence: 99%

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Present and Future of Dyslipidaemia Treatment—A Review

Merćep,

Vujević,

Strikić

et al. 2023

JCM

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“…• If target LDL-C cannot be achieved by low-dose statins, then non-statins such as ezetimibe, bempedoic acid alone or in combination can be utilized for modest LDL-C reduction, or PCSK9 monoclonal antibodies (evolocumab and alirocumab) can be considered for more aggressive LDL-C reduction [1,[46][47][48]. These medications have lower reported musculoskeletal side effects, however, they may require insurance justification to rationalize the need for nonstatin; this could be a high ASCVD score, imaging evidence of ASCVD, and/or documentation of statin intolerance [49].…”

Section: Approaches For Patients With Statin Intolerancementioning

confidence: 99%

Overcoming patient reluctance to statin intolerance

Katamesh,

Mickow,

Huang

et al. 2024

Pol Heart J

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Statin therapy is a cornerstone in the management of dyslipidemia, both in primary and secondary prevention of cardiovascular events. Despite strong guidelines supporting statin use, concerns regarding side effects, particularly musculoskeletal symptoms, contribute to statin intolerance and patient reluctance. While statin intolerance is reported in 5% to 30% of patients, its true prevalence may be overestimated due to the influence of the nocebo effect. Factors associated with higher incidence of statin intolerance include older age, female sex, comorbidities such as diabetes and chronic kidney disease, and concurrent use of medications such as antiarrhythmic agents or calcium channel blockers. Clinical characterization of statin intolerance requires thorough evaluation and exclusion of alternative causes of musculoskeletal symptoms. Strategies to address statin intolerance include reassessing cardiovascular risk, engaging in shared decision-making, statin rechallenge after appropriate washout periods, dosage titration for tolerability, and consideration of alternative therapies when low-density lipoprotein goals cannot be achieved with statins. This review provides an overview of the spectrum of statin intolerance, its clinical assessment, and a systematic approach to caring for a patient with statin intolerance.

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“…The placebo group reported more cases of myalgias, whereas the bempedoic acid group had slightly higher incidences of cholelithiasis, gout, and hyperuricemia. Bempedoic acid seems generally safe, well-tolerated, and linked to minor side effects that are easily remedied (Banach et al, 2023;Nissen et al, 2023;Raschi et al, 2023).…”

Section: Safety Of Bempedoic Acid In Hyperlipidemiamentioning

confidence: 99%

ATP-Citrate Lyase (ACLY): An Extensive Investigation from Molecular Insight to Therapeutic implications

Biju,

Chennam Lakshmikumar,

Rengasamy

2024

NRFHH

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ATP Citrate Lyase (ACLY) is a central enzyme bridging carbohydrate metabolism and lipid biosynthesis, crucial for various physiological processes and implicated in numerous pathologies. This review comprehensively describes ACLY, a pivotal enzyme at lipid biosynthesis and cellular metabolism interface. It serves as crucial role for several physiological functions, making it a highly valued topic for research. Starting with a description of the biochemistry and molecular biology of ACLY, elucidating its structural features, functions, and regulatory mechanisms, particularly in lipid synthesis and histone acetylation. Considering the pathophysiological aspect, the review also examines the relationship between ACLY dysregulation and associated diseases, explaining its contribution to pathological conditions mechanistically. An explanation of ACLY inhibitors is as follows: an overview of these inhibitors, an understanding of their mechanisms of action, and an analysis of their effectiveness and specificity. The following sections transition from preclinical studies, summarising key findings and knowledge into therapeutic potential, to clinical trials. The review offers updated information about ACLY research, integrating data from multiple sources to give an in-depth understanding. It concludes with the challenges and outlook facing the developing ACLY inhibitors, considering the strategies to overcome these challenges and the upcoming path in research and development in this promising field. This comprehensive examination not only encapsulates the knowledge at present but also aims to inspire and guide future inquiries into the complex realm of ACLY and its potential as a therapeutic target, ultimately improving patient outcomes and quality of life.

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Beyond statins: New pharmacological targets to decrease LDL-cholesterol and cardiovascular events

Cited by 23 publications

References 171 publications

Present and Future of Dyslipidaemia Treatment—A Review

Present and Future of Dyslipidaemia Treatment—A Review

Overcoming patient reluctance to statin intolerance

ATP-Citrate Lyase (ACLY): An Extensive Investigation from Molecular Insight to Therapeutic implications

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