Table 1.

Non-statins and their effects on low-density lipoprotein cholesterol and cardiovascular disease end points

class	examples	typical % LDL cholesterol reduction	evidence for clinical CVD end point reduction	key reference(s)	comments
statins	lovastatin, simvastatin, pravastatin, fluvastatin atorvastatin, rosuvastatin, pitavastatin	35–55%	incontrovertible: 22% CVD risk reduction for 1 mmol/L (~40 mg/dL) LDL cholesterol reduction, plus ~10% reduced all-cause mortality	2	reference comparator for non-statin agents in this table
cholesterol absorption inhibitor	ezetimibe	18–25%	strong: modest incremental ~7% reduction when added to statin therapy in acute coronary syndrome patients	32	no studies with ezetimibe as monotherapy
bile acid sequestrants	cholestyramine, colestipol, colesevelam	18–25%	good evidence vs placebo: ~20% CVD risk reduction in events in primary prevention	30,37	no studies with resins added to statins
niacin-based preparations	crystalline niacin (short acting), extended release niacin	20–25%	good evidence vs placebo: ~20% CVD risk reduction in events, with reductions in mortality over longer term; no incremental CVD risk reduction when added to statin therapy in patients with well-treated LDL cholesterol	49–51	multiple effects on lipid profile; neutral outcomes when given to patients well-treated on statin
fibrates	gemfibrozil, fenofibrate, bezafibrate	5–15%, varies depending on baseline triglyceride levels	good evidence vs placebo: ~20% CVD risk reduction in events; no incremental CVD risk reduction when added to statin therapy in patients with well-treated LDL cholesterol	64,66–68	multiple effects on lipid profile; subgroup analyses suggest benefit in men with high TG, low HDL cholesterol
PCSK9 inhibitors	evolocumab, alirocumab, bococizumab	40–65%	promising evidence: ~50% reduction in CVD events when added to statin therapy in aggregated small early phase study results	78,81	possible new standard of therapy; long term outcomes data pending
APOB antisense oligonucleotide	mipomersen	30–45%	no evidence: good efficacy for LDL cholesterol reduction in homozygous familial hypercholesterolemia	94	also lowers Lp(a); injection site reactions, flu-like symptoms
MTP inhibitor	lomitapide	35–50%	no evidence: good efficacy for LDL cholesterol reduction in homozygous familial hypercholesterolemia	97, 98	GI symptoms, fatty liver
CETP inhibitors	anacetrapib, evacetrapib	20–30%	no evidence: awaiting large scale outcomes studies	102, 103	also raise HDL cholesterol by 80–100%
ATP citrate lysase inhibitor	bempedoic acid	20–28%	no evidence: early in development	107	no long term data; apparently well tolerated

abbreviations: APOB, apolipoprotein B; ATP, adenosine triphosphate; CETP, cholesteryl ester transfer protein; CVD, cardiovascular disease; GI, gastrointestinal; HDL, high density lipoprotein; LDL, low density lipoprotein; MTP, microsomal triglyceride transfer protein; PCSK9, proprotein convertase subtilisin kexin 9; TG, triglyceride.