Low-density lipoprotein cholesterol (LDL-C) deposits in artery walls and drives atherosclerotic cardiovascular disease (ASCVD). Lowering LDL-C reduces heart attack and stroke — the lower and the longer, the greater the benefit. Most drugs increase the number of LDL receptors on liver cells, which pull LDL out of the blood.

Reference lipid values (adults, fasting or nonfasting)

Who needs a statin — the main groups:

• Clinical ASCVD (prior MI, stroke, peripheral artery disease) — high-intensity statin
• LDL-C ≥ 190 mg/dL (4.9 mmol/L) or familial hypercholesterolemia
• Diabetes, age 40 or older
• Primary prevention based on calculated 10-year risk (the 2026 US guideline uses the AHA PREVENT equations) and risk enhancers such as coronary artery calcium or high lipoprotein(a)

2026 ACC/AHA dyslipidemia guideline LDL-C goals

Very high risk means ASCVD with ≥ 2 major events (ACS within 12 months, prior MI, prior ischemic stroke, symptomatic peripheral artery disease), or one major event plus ≥ 2 high-risk conditions (age ≥ 65, prior coronary bypass or PCI, current smoking, diabetes, HF, hypertension, LDL-C ≥ 100 mg/dL (2.6 mmol/L) despite maximally tolerated statin + ezetimibe).

The guideline also recommends measuring lipoprotein(a) at least once in every adult.

Statin intensity

Adding a nonstatin drug when LDL-C stays above goal on the maximally tolerated statin: ezetimibe first in most clients, then a PCSK9 monoclonal antibody or inclisiran; bempedoic acid for statin-intolerant clients.

Triglycerides ≥ 500 mg/dL (5.6 mmol/L), and especially ≥ 1,000 mg/dL (11.3 mmol/L), risk acute pancreatitis → very-low-fat diet, alcohol avoidance, glucose control, and fibrate or omega-3 therapy.

Contraindications

• Statins: acute liver failure or decompensated cirrhosis (current US label wording); hypersensitivity.
• Pregnancy and breastfeeding: in 2021 the FDA removed the formal contraindication for statins in all pregnancies, but most clients stop statins when pregnancy is planned or detected, and breastfeeding while on a statin is not recommended. The 2026 guideline advises deferring most lipid-lowering therapy during conception, pregnancy, and lactation; very high-risk clients (e.g., homozygous familial hypercholesterolemia) are managed by a specialist. Bile acid sequestrants are not absorbed and may be used.
• Fibrates: severe kidney or liver disease, gallbladder disease.
• Bile acid sequestrants: cholestyramine — complete biliary obstruction; colesevelam — TG > 500 mg/dL (5.6 mmol/L), history of hypertriglyceridemia-induced pancreatitis, bowel obstruction.

Interactions that raise statin levels → myopathy risk

• Gemfibrozil — avoid with any statin; use fenofibrate if a fibrate is needed
• Strong CYP3A4 inhibitors with simvastatin, lovastatin, and (to a lesser degree) atorvastatin: clarithromycin, erythromycin, itraconazole, ketoconazole, HIV and hepatitis C protease inhibitors — contraindicated with simvastatin/lovastatin
• Large amounts of grapefruit juice (more than about 1 quart/1 liter daily) with simvastatin and lovastatin
• Amiodarone (simvastatin maximum 20 mg), diltiazem and verapamil (simvastatin maximum 10 mg), amlodipine (simvastatin maximum 20 mg)
• Cyclosporine — avoid simvastatin, lovastatin, pitavastatin; limit others
• Colchicine — additive myopathy
• Pravastatin, rosuvastatin, and pitavastatin are not metabolized by CYP3A4 and are preferred when interactions are a concern

Bile acid sequestrant interactions: bind warfarin, levothyroxine, digoxin, thiazides, oral contraceptives, and fat-soluble vitamins. Give other drugs at least 1 hour before or 4–6 hours after cholestyramine (4 hours before colesevelam for several drugs).

Other: statins can slightly raise the INR with warfarin — check INR when starting or changing the dose. Bempedoic acid raises simvastatin and pravastatin levels (limit doses).

1. Baseline lipid panel, then repeat 4–12 weeks after starting or changing therapy to check response and adherence, then every 3–12 months as needed.
2. Liver enzymes (ALT) at baseline; routine repeat testing is not needed — recheck if symptoms of liver injury occur (fatigue, anorexia, abdominal pain, dark urine, jaundice).
3. Creatine kinase (CK) is not routinely monitored; check it for muscle symptoms. CK > 10 times the upper limit of normal with symptoms → stop the statin and evaluate for rhabdomyolysis (creatinine, urine myoglobin).
4. Assess muscle symptoms before labeling a client "statin intolerant" — many can tolerate another statin, a lower dose, or alternate-day dosing.
5. Check glucose or A1C in clients with diabetes risk; check uric acid for bempedoic acid and niacin.
6. Review the medication list for CYP3A4 inhibitors, gemfibrozil, and cyclosporine at every admission.
7. Timing: give simvastatin and lovastatin in the evening (lovastatin immediate-release with the evening meal); atorvastatin, rosuvastatin, and pitavastatin at any consistent time.
8. Bile acid sequestrant powder must be mixed with 4–6 oz (120–180 mL) of fluid — never taken dry (choking, esophageal obstruction).
9. PCSK9 injections: let the pen or syringe reach room temperature (about 30 minutes); SC in abdomen, thigh, or upper arm; rotate sites; refrigerate supply.
10. Reinforce therapeutic lifestyle change — diet, activity, weight, smoking cessation — as the foundation of every regimen.

• Take the statin every day, long term — cholesterol rises again when it is stopped; it has no symptoms to remind you
• Report unexplained muscle pain, tenderness, or weakness, especially with fever or dark (cola-colored) urine — stop and call the provider urgently for these symptoms
• Report yellow skin or eyes, dark urine, or severe fatigue
• Avoid large amounts of grapefruit juice with simvastatin, lovastatin, or atorvastatin; limit alcohol (liver and triglycerides)
• Tell every prescriber you take a statin — some antibiotics and antifungals interact
• Plan pregnancy with the provider; stop the statin and contact the provider if pregnancy occurs; do not breastfeed while taking it unless advised by a specialist
• Diet: limit saturated and trans fat; increase soluble fiber (oats, legumes), vegetables, fruits, and fish; exercise at least 150 minutes per week; lose weight if overweight
• Niacin: flushing is common — taking aspirin 30 minutes before (if allowed) and avoiding hot drinks and alcohol near the dose reduces it
• Cholestyramine: mix with fluid; separate other medicines; increase fluids and fiber for constipation
• Bempedoic acid: report joint pain (gout) or tendon pain

• There is no specific antidote for statins or other lipid-lowering drugs; overdose is treated with supportive care.
• Rhabdomyolysis — the key serious toxicity:
  • Signs: severe muscle pain, weakness, dark red-brown urine, reduced urine output
  • Labs: very high CK, myoglobinuria, hyperkalemia, rising creatinine (acute kidney injury)
  • Management: stop the statin (and interacting drugs), aggressive IV isotonic fluids to maintain urine output as ordered, monitor potassium and ECG, dialysis if kidneys fail
• Hepatotoxicity — stop the drug for clinically significant liver injury or jaundice.
• Bile acid sequestrant overuse — bowel obstruction, vitamin K deficiency with bleeding (prolonged INR).
• Niacin hepatotoxicity is more common with sustained-release products.

• Statins block HMG-CoA reductase; atorvastatin 40–80 or rosuvastatin 20–40 = high intensity
• 2026 US goals: LDL-C < 55 mg/dL (1.4 mmol/L) very high risk; < 70 mg/dL (1.8 mmol/L) high risk
• Statin muscle pain + dark urine → stop and report (rhabdomyolysis); CK > 10 × upper limit
• ALT at baseline, not routinely after; lipid panel 4–12 weeks after a change
• Simvastatin/lovastatin in the evening; avoid grapefruit juice and gemfibrozil
• Statins: stop when planning or in pregnancy; not while breastfeeding
• Add ezetimibe first, then PCSK9 antibody or inclisiran
• Bile acid sequestrants → constipation, bind other drugs (give 1 h before or 4–6 h after)
• Fibrates → gallstones; TG ≥ 500 mg/dL (5.6 mmol/L) → pancreatitis risk
• Niacin → flushing (aspirin 30 min before)
• Measure lipoprotein(a) once in adulthood