Newer cholesterol-lowering agents: What you must know
Considering a non-statin intervention? Choose one that upregulates LDL-C-receptor expression. Adding a PCSK9 inhibitor to statin therapy is effective, but expensive.
PRACTICE RECOMMENDATIONS
› Consider adding ezetimibe to maximally tolerated statin therapy for patients not meeting low-density lipoprotein cholesterol (LDL-C) goals with a statin alone. B
› Limit consideration of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors to adults at highest risk: those with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who must further lower LDL-C levels. A
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
From The Journal of Family Practice | 2018;67(6):339-341,344-345.
CETP inhibitors: Not FDA approved
In a recent trial of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, the drug had favorable effects on lipid biomarkers but did not improve cardiovascular outcomes.28 More recently, the CETP inhibitor anacetrapib was shown to decrease the composite outcome of coronary death, MI, or coronary revascularization in adults with established ASCVD who were receiving high-intensity atorvastatin therapy.13 At the trial midpoint, mean high-density lipoprotein (HDL) cholesterol levels increased by 43 mg/dL in the anacetrapib group compared with that of the placebo group (a relative difference of 104%); mean non-HDL cholesterol decreased by 17 mg/dL, a relative difference of −18%. Over a median follow-up period of 4.1 years, the addition of anacetrapib was associated with a 9% RRR and a 1% absolute reduction in the composite outcome over a statin alone (NNT=100).13 At this point, the manufacturers of both agents have halted efforts to gain FDA approval.
Future directions
Newer strategies to inhibit PCSK9 function are under development. Small peptides that inhibit PCSK9 interaction with the LDL receptor offer the potential advantage of oral administration, as opposed to the currently available injectable anti-PCSK9 antibodies.29 A recent trial found that inhibition of PCSK9 messenger RNA (mRNA) synthesis with the small interfering RNA (siRNA) molecule inclisiran lowered LDL-C in patients with high cardiovascular risk and elevated LDL-C levels despite aggressive statin therapy.30 The effect of these strategies on cardiovascular outcomes remains unproven.
CORRESPONDENCE
Jonathon Firnhaber, MD, Department of Family Medicine, Brody School of Medicine, 101 Heart Drive, Mail Stop 654, Greenville, NC 27834; firnhaberj@ecu.edu.
