Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data

ABSTRACT

Introduction: Cardiovascular (CV) diseases are the leading cause of death and disability in the developed countries. Lipid-lowering therapy is a cornerstone of the CV risk modification strategy. The first line treatment for hyperlipidemia is statins, which decrease low-density lipoprotein cholesterol (LDL-C) by 30–50% and proportionally reduce the CV events. However, they are not always enough to achieve LDL-C goals in many patients, and some patients are statin intolerant. For this reason, new powerful injectable lipid-lowering drugs have been developed.

Areas covered: The aim of this narrative review was to summarize the more recent clinical data on safety and tolerability of injectable lipid-lowering drugs. After an attentive literature search, the authors resumed here information on proprotein convertase subtilisin/kexin 9 inhibitors (evolocumab and alirocumab), small interfering RNA molecule inclisiran, antisense oligonucleotides (mipomersen, volanesorsen, ISIS 681257), and drugs targeting angiopoietin-like protein 3 (evinacumab, IONIS-ANGPTL3_Rx).

Expert opinion: Injectable lipid-lowering therapy for patients at high risk for CV disease complications or with severe inherited hypercholesterolemias can be an important element of the available therapeutic armamentarium. Clinical data prove the favorable risk-benefit profile of evolocumab, alirocumab, and inclisiran. Mipomersen, volanesorsen, ISIS 681257, evinacumab, and IONIS-ANGPTL3_Rx safety is currently less extensively studied, especially in patients with comorbidities and polypharmacotherapy.

KEYWORDS:

• Alirocumab
• evolocumab
• inclisiran
• lipid-lowering therapy
• mipomersen
• volanesorsen

Article highlights

• First line lipid-lowering therapy is represented by statins, but a relatively large number of patients need additional lipid-lowering to improve their lipid control or are statin intolerant.

• The most frequent adverse effects of evolocumab and alirocumab include flu-like symptoms, upper respiratory tract infections, and nasopharyngitis.

• The most common adverse reactions of inclisiran include nasopharyngitis, headache, back pain, cough, musculoskeletal pain, and diarrhea.

• Mipomersen, volanesorsen and ISIS 681257 have alike safety and tolerability profiles, with the most frequent adverse reactions being injection site reactions.

• Evinacumab and IONIS-ANGPTL3_Rx safety need further investigation.

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Declaration of interest

The authors have no 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.