Main nonstatin lipid-lowering therapies
| Agent | Mechanism | Dosing | Cost | Expected lowering of LDL cholesterol | Major prescribing considerations |
|---|---|---|---|---|---|
| Ezetimibe7,10–15 | Inhibition of intestinal cholesterol absorption leads to increased synthesis of LDL receptors and increased LDL cholesterol clearance | Daily oral medication | $ | Monotherapy: 15%–19% With statin therapy: 13%–25% | Generally well tolerated (avoid in hepatic dysfunction) Low cost Available in combination with simvastatin Often first-line recommended nonstatin for lowering LDL |
| Alirocumab, evolocumab7,16–19 | Monoclonal antibodies bind to PCSK9 protein, reducing destruction of LDL receptors and increasing LDL cholesterol clearance | Subcutaneous injection every 2–4 weeks | $$$ | Monotherapy: 50% With statin therapy: 54.7%–70% | Substantially more LDL-lowering than oral options Requires ongoing injections Risk of site reactions Variable insurance coverage may result in high cost |
| Bempedoic acid7,8,20–22 | Inhibition of ATP citrate lyase leads to a reduction in cholesterol biosynthesis, leading to an increase in LDL receptors and to increased LDL cholesterol clearance | Daily oral medication | $$ | Monotherapy: 17.2%–26.5% With statin therapy: 16.5%–18% With ezetimibe: 25%–35% | Generally well tolerated No muscle-related side effects Relatively high cost and variable coverage (may need prior authorization) Available as combination therapy with ezetimibe |
| Inclisiran7,23–26 | Inhibits translation of PCSK9 via RNA interference, reducing destruction of LDL receptors and increasing LDL cholesterol clearance | Subcutaneous injection every 6 months | $$$ | Monotherapy: limited data With statin therapy: 39.7%–52.3% | Twice-yearly dosing may be convenient and desirable High cost and variable coverage Limited access (current ongoing cardiovascular outcomes trials ORION-4 and VICTORION-2P) |
| Bile acid sequestrants7,27 | Less intestinal bile acid absorption leads to an increase in cholesterol converted to bile acid, which leads to an increase in LDL receptors and LDL cholesterol clearance | Daily oral medication | $ | Monotherapy: 15% With statin therapy: additional 10%–16% | Unpalatable agents with gastrointestinal side effects Cardiovascular outcome data older and weaker than other options Not recommended by guidelines to lower LDL cholesterol |
ATP = adenosine triphosphate; LDL = low-density lipoprotein; ORION = A Randomized Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Cardiovascular Disease; PCSK9 = proprotein convertase subtilisin/kexin type 9; VICTORION = A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial, Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Participants With Established Cardiovascular Disease