RESUMO
OBJECTIVE: 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. DATA SOURCES: 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. STUDY SELECTION AND DATA EXTRACTION: 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. DATA SYNTHESIS: 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. CONCLUSION: 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.