# Inclisiran in Dyslipidemia with High Residual Platelet Reactivity

## TL;DR

This paper reviews evidence that inclisiran, a new cholesterol-lowering drug, may help patients with high cardiovascular risk by reducing cholesterol and improving platelet behavior.

## Contribution

The paper introduces inclisiran as a promising treatment for patients with persistent high cholesterol and platelet reactivity despite standard therapy.

## Key findings

- Inclisiran leads to sustained reductions in LDL-C levels in patients unresponsive to conventional therapy.
- Improved cholesterol control may normalize platelet activity in high-risk patients.
- Clinical cases show better control of cholesterol and platelet reactivity after inclisiran treatment.

## Abstract

Despite modern medical treatment, many patients with cardiovascular disease remain at high risk of heart attacks and strokes. This risk is often linked to two persistent problems: high levels of harmful cholesterol and excessive activity of blood platelets, which can promote clot formation even during standard therapy. This review aimed to summarize available evidence and real-world clinical examples evaluating a novel cholesterol-lowering treatment added to conventional care in such high-risk patients. Published studies and patient observations show that this therapy can lead to substantial and sustained reductions in harmful cholesterol levels in individuals who do not reach treatment goals with commonly used drugs. In addition, emerging data suggest that improved cholesterol control may be accompanied by normalization of platelet activity in selected patients with very high cardiovascular risk. Clinical examples illustrate that patients with advanced coronary disease achieved better control of both cholesterol levels and platelet behavior after treatment intensification. These findings highlight the importance of individualized risk assessment using platelet function testing and modern lipid-lowering approaches. Improving control of these key risk factors may help prevent future cardiovascular events and reduce the long-term burden of cardiovascular disease on patients and healthcare systems.

Background: High residual platelet reactivity (HRPR) and persistent dyslipidemia remain important unmet needs in cardiovascular risk management, particularly in patients undergoing coronary revascularization. Despite intensive lipid-lowering and antiplatelet therapy, a substantial proportion of patients fail to reach recommended low-density lipoprotein cholesterol (LDL-C) targets or exhibit inadequate platelet inhibition. Inclisiran, a PCSK9-targeting small interfering RNA, represents an emerging approach for long-term LDL-C reduction. Methods: A narrative review of the literature published between 2009 and 2025 was performed using PubMed, Scopus, Web of Science, and MEDLINE. Studies evaluating the addition of inclisiran to standard lipid-lowering therapy in patients with dyslipidemia and HRPR, assessed using the VerifyNow assay, were included. Illustrative clinical cases from Kazakhstan were analyzed to demonstrate real-world changes in LDL-C levels and platelet reactivity following insufficient response to conventional treatment. The review had a descriptive design. Results: Available evidence indicates that a significant proportion of high- and very-high-risk patients do not achieve LDL-C targets or are unable to tolerate high-intensity statin therapy. Inclisiran consistently induces sustained reductions in LDL-C and circulating PCSK9 levels. Emerging data suggest a potential indirect modulation of platelet reactivity associated with intensive lipid lowering. In patients at extreme cardiovascular risk—including those after coronary artery bypass grafting (CABG) and with long-standing multivessel coronary artery disease—inclisiran therapy was associated with marked LDL-C reduction and a trend toward normalization of platelet reactivity. Conclusions: Assessment of platelet function using the VerifyNow assay may improve identification of residual thrombotic risk in patients with advanced atherosclerotic disease. Inclisiran appears to be a promising adjunctive therapy for dyslipidemic patients with persistently elevated cardiovascular risk and HRPR despite standard treatment. Further prospective studies are warranted to clarify the relationship between intensive LDL-C lowering, platelet reactivity, and clinical outcomes, and to optimize integrated lipid-lowering and antiplatelet strategies.