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Intensive low-density lipoprotein cholesterol lowering in cardiovascular disease prevention: opportunities and challenges
  1. Chris Packard1,
  2. M John Chapman2,
  3. Mahendra Sibartie3,
  4. Ulrich Laufs4,
  5. Luis Masana5
  1. 1 Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
  2. 2 Endocrinology-Metabolism Division, Sorbonne University and Pitié-Salpetriere University Hospital, and National Institute for Health and Medical Research (INSERM), Paris, Île-de-France, France
  3. 3 Amgen Europe, Rotkreuz, Switzerland
  4. 4 Klinik und Poliklinik fur Kardiologie, University Clinic Leipzig, Leipzig, Sachsen, Germany
  5. 5 Vascular Medicine and Metabolism Unit, Sant Joan University Hospital of Reus, Reus, Catalunya, Spain
  1. Correspondence to Chris Packard, University of Glasgow, Glasgow G12 8TA, UK; Chris.Packard{at}


Elevated levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of coronary heart disease and stroke. Guidelines for the management of dyslipidaemia from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) were updated in late 2019 in light of recent intervention trials involving the use of innovative lipid-lowering agents in combination with statins. The new guidelines advocate achieving very low LDL-C levels in individuals at highest risk, within the paradigm of ‘lower is better’. With the advent of combination therapy using ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitors in addition to statins, the routine attainment of extremely low LDL-C levels in the clinic has become a reality. Moreover, clinical trials in this setting have shown that, over the 5–7 years of treatment experience to date, profound LDL-C lowering leads to further reduction in cardiovascular events compared with more moderate lipid lowering, with no associated safety concerns. These reassuring findings are bolstered by genetic studies showing lifelong very low LDL-C levels (<1.4 mmol/L; <55 mg/dL) are associated with lower cardiovascular risk than in the general population, with no known detrimental health effects. Nevertheless, long-term safety studies are required to consolidate the present evidence base. This review summarises key data supporting the ESC/EAS recommendation to reduce markedly LDL-C levels, with aggressive goals for LDL-C in patients at highest risk, and provides expert opinion on its significance for clinical practice.

  • atherosclerosis
  • epidemiology
  • hyperlipidaemias

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  • Contributors All authors contributed equally to the design and writing of the manuscript. All authors critically reviewed and edited the manuscript.

  • Funding Editorial assistance from PharmaGenesis London was funded by Amgen Europe (GmbH). All authors wrote the paper, had full editorial responsibility for the content and did not receive any funding for this work.

  • Competing interests CP has received honoraria from Amgen, Daiichi Sankyo and Dalcor. JC has received research funding from Amgen, Kowa and Pfizer; and honoraria for speakers’ bureau activities and consultancy from Amarin, Amgen, AstraZeneca, Daiichi Sankyo, Merck Sharp & Dohme, Pfizer, Regeneron and Sanofi. UL has received honoraria for lectures from Amgen, Daiichi Sankyo, Novartis and Sanofi. LM has received honoraria for lectures and advisory work from Amarin, Amgen, Amryn, Mylan, Regeneron, Sanofi and Servier. MS is an employee of Amgen.

  • Provenance and peer review Commissioned; externally peer reviewed.

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