Efficacy and safety of add on therapies in patients with hypercholesterolemia undergoing statin therapy

ABSTRACT

Introduction

Statins are the first-line treatment to reduce cardiovascular (CV) events, mainly by reducing low-density-lipoprotein cholesterol (LDL-C), but many patients need additional treatments to reach the current lipid goals.

Areas covered

Herein, the authors review the published literature on the efficacy and safety of the therapies that are most often added to statins to achieve lipid targets.

Expert opinion

Ezetimibe is usually the first additional treatment to achieve LDL-C targets. It reduces LDL-C by about a further 20% and has an excellent safety and tolerability profile. The monoclonal antibody proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab, and alirocumab, can reduce LDL-C by ≥50% when added to statins and they also have a well-established safety and tolerability record. The recently approved bempedoic acid is well tolerated and appears to be free of skeletal muscle-related problems, but the CV outcome study with this drug has not been completed. Inclisiran, a small-interfering RNA targeting PCSK9 is at an advanced stage of development and the available data indicate a satisfactory safety profile and LDL-C lowering efficacy similar to the PCSK9 monoclonal antibodies with the advantage of less frequent administration.

KEYWORDS:

• Alirocumab
• bempedoic acid
• evolocumab
• ezetimibe
• icosapent ethyl
• inclisiran
• proprotein convertase subtilisin/kexin type 9 inhibitors
• statins

Article highlights

• Ezetimibe can be safely added to statin therapy to reduce LDL-C by approximately a further 20%

• The PCSK9 inhibitors, evolocumab and alirocumab, can be added for further reductions in LDL-C by over 50% and they have an excellent safety record.

• Elevated triglycerides represent a residual risk in patients reaching LDL-C targets and these can be treated with icosapent ethyl or fibrates but gemfibrozil-statin combinations should be avoided.

• Bempedoic acid offers a safe alternative for patients with statin intolerance and the combination with ezetimibe shows very effective reduction of LDL-C levels.

• Inclisiran and pemafibrate are being evaluated in phase 3 outcome studies and may provide safe and effective alternatives with cardiovascular benefits by lowering LDL-C or triglycerides, respectively.

• New RNA-directed therapies targeting Lp(a), ANGPTL3 and apoC-III are in development and may prove very effective in selected patients.

This box summarizes key points contained in the article.

Declaration of interest

B Tomlinson has acted as consultant or speaker for Amgen Inc, Kowa, and Merck Serono for which he received honoraria. 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 or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.