An update on PCSK9 inhibitors- pharmacokinetics, drug interactions, and toxicity

ABSTRACT

Introduction

While atherosclerotic cardiovascular disease is affecting growing numbers of patients, lipid-lowering therapies have been continuously improving to achieve prevention of cardiovascular events. Thus, the appearance of a novel therapeutic class, PCSK9 inhibitors, has raised both high expectations as well as concern over possible adverse effects.

Areas covered

This current review aims to analyze adverse events of special interest linked to PCSK9 inhibitors and give recommendations regarding further conduct when dealing with patients on this therapy. The most stringent adverse effect, neurocognitive impairment has been investigated in several studies, concluding that PCSK9 inhibitors neither improved nor worsened cognitive function. While new onset diabetes mellitus has also been a cause of concern due to its possible association with lipid lowering therapies, studies conducted so far have dispelled this possibility by showing that PCSK9 inhibitors do not increase this risk. Also, statin-associated muscle symptoms have not been proven to arise after the use of PCSK9 inhibitors, even in statin-intolerant patients.

Expert opinion

In conclusion, it can be safely stated that so far, no compelling evidence links PCSK9 inhibitors to these adverse events; however, long-term trials are always welcome to further assess potential adverse effects.

KEYWORDS:

• Adverse events
• lipid-lowering therapy
• PCSK9 inhibitors
• neurocognitive events

Article highlights

• Ever since their public launch among lipid lowering therapies more than a decade ago, PCSK9 inhibitors have come under close scrutiny both from scientists and doctors alike, for their potential in reducing LDL-cholesterol levels far below any statin or other drug was able to achieve so far.

• So far no compelling evidence regarding neurocognitive treatment emergent adverse events has been demonstrated, thus physicians are prompted to use this lipid lowering therapy when the clinical situation calls for it.

• While new onset diabetes mellitus was a huge cause of concern regarding a possible side effect of PCSK9 inhibitors, trials and metanalyses performed so far have dispelled this fear by showing that this therapeutic class does not increase the risk for new onset diabetes mellitus and are safe to be used.

• Despite concern over possible muscle related adverse events, PCSK9 inhibitors have proven to be a safe medication which can be administered even to statin intolerant patients, much more having in view that most SAMS are actually patient related and do not stand the test of randomized controlled trials.

• Until such time that novel genetic therapies are developed well enough to be tested on humans, PCSK9 inhibitors remain the newest yet safe weapon which clinicians have at their disposal in the battle against atherosclerotic disease.

Declaration of interest

M Banach has received speakers bureau from Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Polpharma, Sanofi-Aventis, Servier and Valeant; provided consultancy to Abbott Vascular, Akcea, Amgen, Daichii Sankyo, Esperion, Freia Pharmaceuticals, Lilly, MSD, Polfarmex, Resverlogix, Sanofi-Aventis; received grants from Sanofi and Valeant. D Gaiţă has received speakers bureau from Amgen, AstraZeneca, MSD, Mylan, Pfizer, Sanofi and Servier. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.