The Role of Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors in the Management of Dyslipidemia

Title:The Role of Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors in the Management of Dyslipidemia

Volume: 23 Issue: 10

Author(s): Konstantinos Tziomalos*

Affiliation:

• First Propedeutic Department of Internal Medicine, AHEPA Hospital, 1 Stilponos Kyriakidi street, Thessaloniki, 54636,Greece

Keywords: Proprotein convertase subtilisin-kexin type 9 inhibitors, alirocumab, evolocumab, cardiovascular disease, statin intolerance, familial hypercholesterolemia, dyslipidemia.

Abstract: Background: Treatment with statins substantially reduces cardiovascular morbidity and mortality both in patients with and without established cardiovascular disease. Accordingly, statins represent the cornerstone of lipid-lowering treatment. However, there are still unmet clinical needs in the management of dyslipidemia. Indeed, it is difficult to achieve low-density lipoprotein cholesterol (LDL-C) targets in many patients, particularly in those at very high cardiovascular risk or in those with very high baseline LDL-C levels [e.g. with heterozygous familial hypercholesterolemia (FH)]. Moreover, a sizable proportion of patients are not able to tolerate high doses of statins, mostly due to muscle-related adverse effects. In these patient populations, inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) with monoclonal antibodies appears to represent a useful tool for achieving LDL-C targets.

Methods: In the present review, we summarize the current knowledge on the effects of the PCSK9 inhibitors alirocumab and evolocumab on lipid levels in various populations and discuss the role of these agents in the management of dyslipidemia. Results: In addition to a substantial reduction in LDL-C levels (by 50-60%), PCSK9 inhibitors also lower triglyceride, non-high-density lipoprotein cholesterol (non-HDL-C) and lipoprotein (a) levels and increase HDL-C levels. Preliminary data suggest that PCSK9 inhibitors are safe. However, ongoing randomized, placebo-controlled trials will provide definitive evidence on the safety of these novel agents and on their effects on cardiovascular morbidity and mortality.

Conclusion: Given the high cost of PCSK9 inhibitors, their use should be restricted to carefully selected, veryhigh risk patients until the results of these trials are available.

Cite this article as:

Tziomalos Konstantinos*, The Role of Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors in the Management of Dyslipidemia, Current Pharmaceutical Design 2017; 23 (10) . https://dx.doi.org/10.2174/1381612823666170201161631

DOI https://dx.doi.org/10.2174/1381612823666170201161631	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286