Non-Statin Lipid–Lowering Drugs*

Drugs

Comments

Adenosine triphosphate citrate lyase inhibitor

Lowers LDL-C

Risk of hyperuricemia, tendon rupture

Especially useful in patients with statin-associated muscle adverse effects as the enzyme required to activate this drug is absent in the muscle

Bile acid sequestrants

Lower LDL-C (primary), slightly increase HDL-C (secondary), may increase TGs

Cholesterol absorption inhibitor

Lowers LDL-C (primary), minimally increases HDL-C

Drugs for homozygous familial hypercholesteremia

Given as an intravenous infusion over 60 minutes

Adverse reactions in clinical trials include nasopharyngitis, influenza-like illness, and infusion reaction

Risk of hepatotoxicity

Increase dose gradually (about every 2 weeks)

Measure transaminase levels before increasing dosage

Fibrates

Lower TGs and VLDL, increase HDL-C, may increase LDL-C (in patients with high TGs)

Bezafibrate

Decreased dose required in renal insufficiency

Not available in US

Ciprofibrate

Not available in US

Decreased dose required in renal insufficiency

May be safest fibrate for use with statins

Decreased dose required in renal insufficiency

Increases HDL-C; lowers TGs (low doses), LDL-C (higher doses), and Lp(a) (secondary)

Frequent adverse effects: Flushing, impaired glucose tolerance, increased uric acid

Aspirin and administration with food minimize flushing

PCSK9 monoclonal antibodies

For patients with familial hypercholesterolemia and for other high-risk patients

For patients with familial hypercholesterolemia and for other high-risk patients

Prescription omega-3 fatty acids

Eicosapentaenoic acid ethyl ester (EPA) + Docosahexaenoic acid (DHA)

Lowers TGs

Increases LDL-C

Eicosapentaenoic acid ethyl ester (EPA) only

Lowers TGs only

SiRNA targeting PCSK9

For patients with familial hypercholesterolemia and for other high-risk patients

* Many of these drugs are also available in combination with a statin.

HDL = high-density lipoprotein; HDL-C = HDL cholesterol; LDL = low-density lipoprotein; LDL-C = LDL cholesterol; Lp(a) = lipoprotein (a); PCSK9 = proprotein convertase subtilisin-like/kexin type 9; SiRNA = small interfering ribonucleic acid; TG = triglyceride; VLDL = very low-density lipoprotein.

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