PCSK9 inhibitors and cardiovascular outcomes

ABSTRACT

Introduction: Dyslipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C), is a key risk factor for atherosclerotic cardiovascular disease (ASCVD), and lipid-lowering drugs are beneficial for the primary and secondary prevention of cardiovascular (CV) disease. While statins are clear first-line drugs, new drug developments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes when added to statins. Evolocumab reduced the risk of cardiovascular events in patients with ASCVD when added to maximally tolerated statin therapy (± ezetimibe), and recent data from the ODYSSEY OUTCOMES trial indicate that alirocumab added to maximally tolerated statin therapy (± other lipid-lowering drugs) reduces the risk of cardiovascular events in patients with a recent acute coronary syndrome. In this article the authors review the available data on the effect of PCSK9 inhibitors on cardiovascular outcomes.

Areas covered: This article reviews the available data on the effect of PCSK9 inhibitors on CV outcomes. Relevant papers were identified from a search of PubMed/Medline and the Cochrane Central Register of Controlled Trials (CENTRAL).

Expert opinion: The authors conclude that PCSK9 inhibitors provide substantial and durable reductions in LDL-C levels and improve cardiovascular outcomes.

KEYWORDS:

• PCSK9 inhibitors
• alirocumab
• evolocumab
• bococizumab
• cardiovascular outcomes

Article highlights

• Approved proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provide substantial and durable reductions in low-density lipoprotein cholesterol (LDL-C) levels and are generally safe and well tolerated.

• Alirocumab and evolocumab reduce the risk of major adverse cardiovascular events when added to statins.

• Evolocumab added to maximally tolerated statin therapy (± ezetimibe) reduced the risk of cardiovascular (CV) events in patients with atherosclerotic cardiovascular disease (ASCVD).

• Alirocumab added to maximally tolerated statin therapy (± other lipid-lowering drugs) reduced the risk of CV events in patients with a recent acute coronary syndrome (ACS).

• Several large trials are underway which may provide additional data on the role of PCSK9 inhibitors with respect to CV outcomes (EVOPACS study; evaluating the LDL-lowering effect of evolocumab added to statins in the early period after an ACS; PACMAN-AMI and ODYSSEY J-IVUS trials, evaluating the effect of alirocumab on atheroma volume after an acute myocardial infarction/ACS.

This box summarizes key points contained in the article.

Declaration of interest

P Bramlage and U Rauch-Kröhnert received research support and/or lecture fees from both Amgen and Sanofi, the makers of two PCSK9 inhibitors. 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 apart from those disclosed.

Reviewer Disclosures

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

Authors’ contributions

DS, PB, and URK developed the concept for the current review, DS and PB collated all the data and wrote the first draft of the manuscript which all authors revised for important intellectual content. All authors gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.

Additional information

Funding

This paper was not funded.