PCSK9 inhibitors in the prevention of vascular events - a review of current evidence
DOI:
https://doi.org/10.12775/JEHS.2026.89.70057Keywords
PCSK9 inhibitors, evolocumab, alirocumab, inclisiran, cardiovascular prevention, LDL-CAbstract
Background. Atherosclerotic cardiovascular disease remains the leading cause of mortality worldwide. Despite the widespread use of high-intensity statins, many patients fail to achieve target low-density lipoprotein cholesterol (LDL-C) levels and remain at high residual risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a novel class of lipid-lowering therapies that significantly reduce LDL-C and cardiovascular risk.
Aim. This review summarizes current evidence on the efficacy, safety, and clinical application of PCSK9 inhibitors, including monoclonal antibodies, small interfering RNA, and emerging oral agents, in preventing cardiovascular and cerebrovascular events.
Material and methods. A narrative review of literature from PubMed/MEDLINE, Embase, and Cochrane Library databases (January 2015–November 2025) was conducted. Search terms included “PCSK9 inhibitors,” “evolocumab,” “alirocumab,” “inclisiran,” “cardiovascular outcomes,” and “MACE.” Priority was given to randomized controlled trials, systematic reviews, and clinical guidelines.
Results. Monoclonal antibodies (evolocumab, alirocumab) reduce LDL-C by ~60% and major adverse cardiovascular events by 15–20% in secondary prevention. The VESALIUS-CV trial (2025) showed a 25% reduction in first cardiovascular events in high-risk primary prevention. Inclisiran enables sustained lipid reduction with twice-yearly dosing. Emerging oral agents (e.g., enlicitide) show comparable efficacy. Data from over 90,000 patients confirm a favorable safety profile without significant neurocognitive or diabetes-related risks.
Conclusions. PCSK9 inhibitors are effective and safe in reducing vascular events. Their role is expanding from secondary to primary prevention in high-risk or statin-intolerant patients. Future research should address long-term outcomes and novel approaches such as gene-editing therapies.
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