How these drugs actually work
For approval status and trial data, see Therapies. This page is about mechanism only — what each drug class does inside the body.
Statins
Atorvastatin, rosuvastatin, and others
Block HMG-CoA reductase, the liver enzyme that makes cholesterol. With less cholesterol made internally, the liver pulls more LDL out of the blood to compensate.
Lowers: LDL cholesterol, and modestly, triglycerides.
Cholesterol absorption inhibitors
Ezetimibe
Block a transporter in the small intestine that absorbs dietary and bile-derived cholesterol, so less of it reaches the bloodstream in the first place.
Lowers: LDL cholesterol, usually added on top of a statin.
PCSK9 inhibitors
Evolocumab (Repatha), alirocumab (Praluent) — antibodies; inclisiran (Leqvio) — siRNA; enlicitide (Lipfendra) — oral; lerodalcibep (Lerochol) — third-generation protein
PCSK9 is a protein that marks LDL receptors on liver cells for destruction. Blocking it, or blocking its production, leaves more LDL receptors on the liver surface to clear LDL from the blood. The four approaches differ in how they block PCSK9 and how long the effect lasts, which is what drives the different dosing schedules (every 2-4 weeks, twice yearly, daily, or monthly).
Lowers: LDL cholesterol by roughly 50-60%, and lipoprotein(a) by about 20-30% as a secondary effect.
ACL (ATP-citrate lyase) inhibitors
Bempedoic acid (Nexletol)
Blocks an enzyme in the same cholesterol-production pathway as statins, but one step earlier, and is only activated in the liver, not in muscle tissue — which is why it isn't associated with the muscle-related side effects statins can cause.
Lowers: LDL cholesterol, often used for statin-intolerant patients.
CETP inhibitors
Obicetrapib
Block a protein (CETP) that normally shuttles cholesterol from HDL particles to LDL particles. Blocking it raises HDL and lowers LDL at the same time.
Lowers: LDL cholesterol; raises HDL cholesterol.
Lp(a)-targeted therapies
Olpasiran, lepodisiran, zerlasiran (siRNA); muvalaplin (oral)
The siRNA drugs block the liver from producing the protein components of lipoprotein(a) in the first place. Muvalaplin instead blocks the two particle components from assembling into Lp(a) after they're made. Unlike statins or PCSK9 inhibitors, none of these were designed to lower LDL — Lp(a) is a separate, largely genetically-determined risk factor that existing therapies barely touch.
Lowers: Lipoprotein(a), often by 80% or more in trials so far. None are FDA-approved yet — see the Therapies page for where each stands.