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
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.
