Review article

https://doi.org/10.15836/ccar.2016.330

Disadvantages of Current LDL-cholesterol Lowering and the Role of PCSK9 Inhibitors.

Sanja Matijević Rončević orcid.org/0000-0003-0627-2114 ; University of Rijeka School of Medicine, University Hospital Centre Rijeka, Rijeka, Croatia
David Gobić orcid.org/0000-0001-9406-1127 ; University of Rijeka School of Medicine, University Hospital Centre Rijeka, Rijeka, Croatia
Teodora Zaninović Jurjević ; University of Rijeka School of Medicine, University Hospital Centre Rijeka, Rijeka, Croatia
Željka Rubeša Miculinić orcid.org/0000-0002-1880-1493 ; University of Rijeka School of Medicine, University Hospital Centre Rijeka, Rijeka, Croatia
Luka Zaputović orcid.org/0000-0001-9415-9618 ; University of Rijeka School of Medicine, University Hospital Centre Rijeka, Rijeka, Croatia

Abstract

LDL cholesterol (LDL-C) is a strong independent cardiovascular (CV) risk factor that can be easily influenced. Today, statins are the therapy of choice for the achievement of target LDL-C values. Although controlled clinical trials have demonstrated their effectiveness and safety, in practice we are often met with statin intolerance as well as a failure to achieve target LDL-C values in a significant portion of the patients despite maximal doses. In patients with high and very high CV risk, other antilipemic pharmacotherapy is often also insufficient. PCSK9 inhibitors (PCSK9-I) are new revolutionary drugs with a potent effect on LDL-C. The rapid development of PCSK9-I began in 2003 with the discovery of a PCSK9 gene mutation in patients with familial hypercholesterolemia. The product of this gene, proprotein convertase subtilisin/kexin type 9 (PCSK9), has an important role in the expression of LDL receptors and cholesterol metabolism. Animal models demonstrated that inactivation of the PCSK9 gene lowers LDL-C with regression of atherosclerotic changes in the aorta. Heterozygotes and homozygotes with the inactivation mutation of PCSK9 have lower LDL-C values and lower incidence of atherosclerosis. Among the various groups of PCSK9-I, monoclonal antibodies saw strong development (alirocumab, evolocumab, bococizumab). Phase 3 clinical trials on familial and primary hypercholesterolemia with statin intolerance or resistance have demonstrated a strong positive effect of alirocumab and evolocumab on LDL-C values (a reduction of 60%), with high safety and good tolerability. The OSLER study on evolocumab also demonstrated positive effects on CV outcomes. Multiple clinical trials on PCSK9-I are currently monitoring their effect on CV morbidity and mortality. Positive results from these studies would confirm the great potential of PCSK9-I for better prevention and treatment of CV diseases.

Keywords

cardiovascular diseases; dyslipidemia; LDL-cholesterol; statins; PCSK9 inhibitors

Hrčak ID:

161842

URI

https://hrcak.srce.hr/161842

Publication date:

14.7.2016.

Article data in other languages: croatian

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