Pharmacotherapy
Lipid-Lowering Medications
A class-by-class overview of the drugs used to lower atherogenic lipoproteins and triglycerides — what they target, how they work, and the adverse effects clinicians and patients should know.
Statins (HMG-CoA reductase inhibitors)
Atorvastatin · Rosuvastatin · Simvastatin · Pravastatin · Pitavastatin
3 lipid targets
Lipid effect
LDL-C↓ 30–55%Triglycerides↓ 10–30%ApoB↓ 25–45%
In plain language
Statins are the foundation of cholesterol-lowering therapy. They reduce LDL ("bad") cholesterol and have the strongest evidence for preventing heart attacks and strokes.
Clinical detail
First-line therapy for both primary and secondary ASCVD prevention. High-intensity dosing (atorvastatin 40–80 mg, rosuvastatin 20–40 mg) is recommended in established ASCVD, LDL ≥190 mg/dL, diabetes with elevated risk, and intermediate-to-high PREVENT/PCE risk.
Side effects & adverse events
Monitoring: Baseline lipid panel, ALT, and CK if symptomatic. Recheck lipids 4–12 weeks after initiation or dose change.
Ezetimibe (Zetia)
Ezetimibe 10 mg daily
2 lipid targets
Lipid effect
LDL-C↓ 15–25%ApoB↓ ~15%
In plain language
Ezetimibe blocks cholesterol absorption from the gut. It's well-tolerated and often added to a statin when LDL goals aren't reached.
Clinical detail
Second-line add-on after maximally tolerated statin therapy. IMPROVE-IT demonstrated incremental ASCVD event reduction when added to simvastatin in post-ACS patients.
Side effects & adverse events
Bempedoic acid
Nexletol · Nexlizet (with ezetimibe)
2 lipid targets
Lipid effect
LDL-C↓ 15–25%ApoB↓ ~15%
In plain language
Bempedoic acid lowers LDL through a pathway similar to statins, but it is only activated in the liver — so it tends to cause fewer muscle symptoms. Useful for patients who can't tolerate statins.
Clinical detail
Indicated for statin-intolerant patients or as add-on to maximally tolerated statin. CLEAR Outcomes (2023) demonstrated MACE reduction in a statin-intolerant primary- and secondary-prevention population.
Side effects & adverse events
PCSK9 inhibitors
Evolocumab (Repatha) — monoclonal antibody, SC q2–4 weeks · Alirocumab (Praluent) — monoclonal antibody, SC q2 weeks · Inclisiran (Leqvio) — siRNA, SC q6 months after loading
3 lipid targets
Lipid effect
LDL-C↓ 50–60%Lp(a)↓ 20–30%ApoB↓ ~50%
In plain language
PCSK9 inhibitors are injectable medications that produce the deepest LDL lowering available. They're typically reserved for high-risk patients who need more reduction than statins and ezetimibe can provide.
Clinical detail
Add-on for established ASCVD, familial hypercholesterolemia, or very-high-risk patients not at goal on maximally tolerated statin ± ezetimibe. FOURIER (evolocumab) and ODYSSEY OUTCOMES (alirocumab) demonstrated MACE reduction. Inclisiran offers twice-yearly dosing via hepatic siRNA silencing of PCSK9 mRNA.
Side effects & adverse events
Fibrates
Fenofibrate · Gemfibrozil
3 lipid targets
Lipid effect
Triglycerides↓ 30–50%HDL-C↑ 5–15%LDL-CVariable (may rise in hypertriglyceridemia)
In plain language
Fibrates mainly lower triglycerides. They're used most often when triglycerides are very high (≥500 mg/dL) to reduce the risk of pancreatitis.
Clinical detail
Primarily for severe hypertriglyceridemia (TG ≥500 mg/dL) to mitigate pancreatitis risk. ASCVD outcome data are mixed: FIELD and ACCORD-Lipid were neutral overall, with possible benefit in atherogenic dyslipidemia subgroups. PROMINENT (pemafibrate) was neutral.
Side effects & adverse events
Niacin (Nicotinic acid)
Immediate-release niacin · Extended-release niacin (Niaspan)
4 lipid targets
Lipid effect
LDL-C↓ 5–25%Triglycerides↓ 20–50%HDL-C↑ 15–35%Lp(a)↓ 20–30%
In plain language
Niacin can favorably shift several lipid markers, but large outcome trials did not show added benefit when given on top of a statin — and it causes bothersome flushing. It's rarely used today.
Clinical detail
Largely fallen out of favor: AIM-HIGH and HPS2-THRIVE failed to demonstrate ASCVD event reduction added to statin therapy, and HPS2-THRIVE showed an increase in serious adverse events. Occasionally considered in highly selected refractory dyslipidemia.
Side effects & adverse events
Bile acid sequestrants
Cholestyramine · Colestipol · Colesevelam
2 lipid targets
Lipid effect
LDL-C↓ 15–25%TriglyceridesMay rise — avoid in hypertriglyceridemia
In plain language
These powders or tablets bind bile acids in the gut so the body must make more from cholesterol, lowering LDL. They aren't absorbed into the bloodstream, which can make them useful in pregnancy or when systemic side effects are a concern.
Clinical detail
Niche use: pregnancy, statin intolerance, pruritus of cholestasis, and adjunctive LDL lowering. Colesevelam additionally improves glycemic control modestly in T2DM.
Side effects & adverse events
Icosapent ethyl (Vascepa)
Icosapent ethyl 2 g BID (purified EPA only)
1 lipid target
Lipid effect
Triglycerides↓ 20–30%
In plain language
Vascepa is a purified form of an omega-3 fatty acid (EPA). Unlike over-the-counter fish oil, it has been shown in a large clinical trial to reduce heart attacks and strokes in certain high-risk patients with elevated triglycerides.
Clinical detail
REDUCE-IT demonstrated 25% relative MACE reduction in statin-treated patients with TG 135–499 mg/dL and either established ASCVD or diabetes with risk factors. Mixed EPA/DHA formulations (e.g., omega-3 acid ethyl esters) and OTC fish oil have NOT shown the same outcome benefit (STRENGTH trial was neutral).
Side effects & adverse events
Educational content only
Drug selection, dose, and combinations require individualized clinical judgment. Always consult a qualified clinician before starting, stopping, or modifying any medication.