The Role of PCSK9 Inhibitors in the Treatment of Hypercholesterolemia

To evaluate the efficacy, safety, and cost-effectiveness of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and describe its place in therapy for the treatment of hypercholesterolemia.

A search of MEDLINE, CINAHL, and Clinicaltrials.gov was performed from January 2012 to March 2018 to identify literature pertaining to PCSK9 inhibitors using pre-specified search terms. Additional references were identified from citations of the literature.

Only articles in English were reviewed. Phase II, phase III, pooled, post hoc, and cardiovascular (CV) trials were included. Cost-effectiveness studies and conference materials were also reviewed.

All trials evaluating alirocumab and evolocumab demonstrated significant low-density lipoprotein cholesterol (LDL-C) lowering versus comparators. Two trials revealed a decrease in the major adverse cardiovascular events (MACE) end point with PCSK9 inhibitor use; 1 of these 2 trials revealed a decrease in all-cause mortality with alirocumab use. No significant safety concerns apart from injection site reactions were noted. Despite these results, 4 cost-effectiveness analyses failed to meet acceptable thresholds. Relevance to Patient Care and Clinical Practice: This review describes the most up-to-date evidence regarding PCSK9 inhibitors. A discussion on LDL-C lowering potential, effect on CV events and mortality, safety considerations, feasibility of administration, and cost are included to guide clinicians on future use.

The PCSK9 inhibitor drug class is an effective LDL-C lowering option for patients with the highest risk of CVD events and high LDL-C despite the use of statin therapy. For more widespread use, significant cost reductions are needed.