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Review Article
Re-evaluating the PCSK9 guidelines for low-density lipoprotein cholesterol targets: weighing the benefits against the risks
Terry Gbaa, John Bolodeoku
Cardiovasc Prev Pharmacother. 2024;6(3):85-91.   Published online July 30, 2024
DOI: https://doi.org/10.36011/cpp.2024.6.e11
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Cardiovascular disease management has made significant progress with lipid-lowering interventions, primarily statin therapy. However, statins' side effects, combined with their variable efficacy, have sparked interest in alternative treatments, particularly proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies. These biologics, approved by the US Food and Drug Administration and the European Medicines Agency, have shown a significant impact on lipid levels, particularly low-density lipoprotein cholesterol (LDL-C), resulting in a 50% to 60% reduction. Despite the benefits of PCSK9 inhibitors, the guidelines for their use differ, with specific thresholds determining eligibility. The National Institute for Health and Care Excellence recommends starting PCSK9 therapy for patients with LDL-C levels above 3.5 mmol/L and lipid levels above 5.0 mmol/L who do not have cardiovascular disease. This rigid framework, while cost-effective, may exclude a subset of patients who do not meet these criteria despite having a high cardiovascular risk. The limited scope of these guidelines presents a challenge for specialists managing patients excluded as a result of LDL-C levels that fall just below the threshold but still show signs of significant cardiovascular risk. Recent audits revealed that a significant proportion of patients fall into this grey area, emphasizing the importance of re-evaluating LDL targets for PCSK9 inhibitor initiation. Biological variations, pharmacogenomics, and other factors all contribute to this challenge, highlighting the importance of personalized medicine.

CPP : Cardiovascular Prevention and Pharmacotherapy
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