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Is Our Increasing Understanding of PCSK9 and Lp(a) Metabolism the Key to Unlocking the Paradox of Statins Ineffectiveness in Reducing Cardiovascular Events in Advanced CKD?

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Abstract

Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD) and dialysis patients. This association may be attributed to the highly atherogenic dyslipidemia, which is characteristically present in these patients. Despite their proven benefit on cardiovascular outcomes in the general population, statin-based therapies have proven less effective in patients with CKD. Recent discoveries in the physiology of lipid metabolism, regarding the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipoprotein (a) [Lp(a)] in atherosclerosis have provided new perspectives. Data from randomized trials in the general population testing the efficacy and safety of novel drug therapies, specifically targeting these molecules, indicate significant reductions in cardiovascular events and mortality. However, patients with reduced renal function, who may benefit the most from such treatments, were excluded from these studies, making these therapeutic approaches inapplicable to this complicated population. There is an urgent call for further studies to examine whether new treatments such as those targeting PCSK9 would manage to decrease the high cardiovascular mortality rates in CKD and dialysis patients.

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Authors and Affiliations

  1. Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Charalampos Loutradis & Pantelis A. Sarafidis

  2. Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2WB, UK

    Charalampos Loutradis & Charles J. Ferro

  3. Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain

    Alberto Ortiz

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  1. Charalampos Loutradis
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  2. Pantelis A. Sarafidis
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  3. Alberto Ortiz
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  4. Charles J. Ferro
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CL and CJF drafted the manuscript and performed the revisions, PAS updated the literature, AO performed critical analysis of the manuscript, and CJF provided supervision and mentorship.

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Correspondence to Charalampos Loutradis.

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Loutradis, C., Sarafidis, P.A., Ortiz, A. et al. Is Our Increasing Understanding of PCSK9 and Lp(a) Metabolism the Key to Unlocking the Paradox of Statins Ineffectiveness in Reducing Cardiovascular Events in Advanced CKD?. SN Compr. Clin. Med. 4, 145 (2022). https://doi.org/10.1007/s42399-022-01242-w

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