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Overall Mortality and LDL Cholesterol Reduction in Secondary Prevention Trials of Cardiovascular Disease

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Abstract

Pooled data from randomized clinical trials on lipid-lowering therapy have provided valuable information and clinical insights. Although cardiovascular disease is a common cause of death, mortality data have rarely been prominent in key lipid trials. The 4S, LIPID and HPS trials were the first to demonstrate a reduction in overall mortality. Lower- versus higher-intensity statin trials and non-statin lipid-lowering trials with ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors proved that additional lipid lowering significantly reduces the occurrence of cardiovascular events. However, only the ODYSSEY OUTCOMES trial showed a reduction in all-cause mortality. The aim of the present narrative review was to contrast these results with those of other key lipid trials: those assessing statins compared with placebo, those evaluating intensive- versus moderate-intensity lipid-lowering therapy and, finally, those investigating non-statin lipid-lowering therapies.

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Acknowledgements

The authors thank the Sociedad Española de Arteriosclerosis for scientific support and Miss Christine O’Hara for review of the English version of the manuscript.

Funding

The authors received no financial support for the research, authorship and/or publication of this article.

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Authors and Affiliations

  1. Unitat de Lípids i Risc Vascular, Department of Medicine, Hospital del Mar, Universitat Autònoma de Barcelona, Passeig Marítim, 25-29, 08003, Barcelona, Spain

    Juan Pedro-Botet

  2. Lipid and Atherosclerosis Unit, Department of Internal Medicine/IMIBIC/Reina Sofia University Hospital/University of Cordoba, CIBEROBN, Cordoba, Spain

    Jose López-Miranda

  3. Cardiovascular Program ICCC-IR-Hospital de la Santa Creu i Sant Pau, CiberCV, IIB-Sant Pau, Barcelona, Spain

    Lina Badimón

  4. Unidad de Lípidos, Hospital Universitario Miguel Servet, IIS Aragón, CIBERCV, Universidad de Zaragoza, Zaragoza, Spain

    Fernando Civeira

  5. Internal Medicine Unit, University Hospital Alcorcon Foundation, Rey Juan Carlos University, Madrid, Spain

    Carlos Guijarro

  6. Lipid Unit, Department of Internal Medicine, Hospital Universitario General Gregorio Marañón, Universidad Complutense, Madrid, Spain

    Jesús Millán

  7. Internal Medicine Service, Hospital Carlos III, Madrid, Spain

    Jose M. Mostaza

  8. Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain

    Xavier Pintó

  9. Department of Medicine and Dermatology, Lipids and Atherosclerosis Laboratory, CIMES, University of Málaga, Virgen de La Victoria University Hospital, IBIMA, Málaga, Spain

    Pedro Valdivielso

  10. Unitat de Medicina Vascular i Metabolisme, Hospital Universitari Sant Joan, Universitat Rovira i Virgili, IISPV, CIBERDEM, Reus, Spain

    Luis Masana

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  1. Juan Pedro-Botet
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Expert group from the Spanish Arteriosclerosis Society

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Correspondence to Juan Pedro-Botet.

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Conflicts of interest

Juan Pedro-Botet has received consulting fees from Amgen, Mylan and Sanofi and payment for lectures from Amgen, Astra-Zeneca, Esteve, Ferrer, MSD, Mylan and Sanofi. Jose López-Miranda has received consulting fees and payment for lectures from Amgen, Boehringer Ingelheim-Lilly, Esteve, Ferrer and Sanofi. Lina Badimón has received advisory board fees from Sanofi. Fernando Civeira has received consulting fees from Amgen and Sanofi and payment for lectures from Sanofi, Ferrer and Merck. Carlos Guijarro has received honoraria for speaker lectures and participation on advisory committees with Amgen and Sanofi. Jesús Millán has received consulting fees from Mylan and Sanofi and payment for lectures from Amgen, Esteve, MSD, Mylan and Sanofi. Jose Mostaza has received consulting fees and payment for lectures from Amgen and Sanofi. Xavier Pintó has received consulting fees from Amgen, Esteve, Ferrer, Mylan, Rubió and Sanofi and payment for lectures from Esteve, Ferrer, Mylan, Rubió and Sanofi. Pedro Valdivielso has received consulting fees from Amgen and Sanofi and payment for lectures from Almirall, Esteve, Ferrer, MSD and Sanofi. Luis Masana has received consulting fees from Amgen, Daiichi Sankyo and Sanofi and payment for lectures from Amgen, MSD and Sanofi.

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Pedro-Botet, J., López-Miranda, J., Badimón, L. et al. Overall Mortality and LDL Cholesterol Reduction in Secondary Prevention Trials of Cardiovascular Disease. Am J Cardiovasc Drugs 20, 325–332 (2020). https://doi.org/10.1007/s40256-019-00376-y

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