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Second-line lipid-lowering agents

Last updated: August 10, 2021

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Second-line lipid-lowering agents include fibrates, bile acid resins, niacin, and cholesterol absorption inhibitors. These drugs are used concurrently with statins for patients who have hypercholesterolemia that is inadequately controlled with statin monotherapy. They are also used as second-line agents for patients who experience persistent side effects from statins (e.g., myositis, myalgias, and/or myopathy). Each drug targets different steps in the cholesterol and lipid metabolism pathways to treat hypercholesterolemia and, therefore, vary in their effectiveness at decreasing low-density lipoprotein (LDL), increasing high-density lipoprotein (HDL), and decreasing triglycerides. Second-line lipid-lowering agents are rarely indicated for primary prevention of cardiovascular disease because they do not improve cardiovascular outcomes or mortality.

Overview of lipid-lowering agents
Agents Indications Mechanism of action Effects on lipid profile Adverse effects Contraindications Interactions
LDL HDL Triglycerides
Statins (e.g., atorvastatin, simvastatin)
  • ↓↓↓
  • Other lipid-lowering agents
  • CYP3A4 inhibitors
PCSK9 inhibitors (e.g., alirocumab, evolocumab)
  • History of hypersensitivity [1]

Bile acid sequestrants (e.g., cholestyramine, colestipol)

  • ↓↓
  • (↑)
  • (↑)
  • Nausea, abdominal bloating, and cramping


  • ↑/↔︎
  • ↓/↔︎
  • Coadministration with a statin during active liver disease
  • ↑↑
Fibrates (e.g., bezafibrate, fenofibrate, gemfibrozil)
  • ↓↓↓
Marine omega-3 fatty acids (fish oil)
  • Add-on therapy
  • (↑)
  • (↑)
  • ↓ (high doses necessary)
  • Hypersensitivity to ingredients of drug formula


  • ↔︎
  • ↔︎
  • Gastrointestinal symptoms
  • LFTs

Marine omega-3 fatty acids (fish oil)


  1. PRALUENT(alirocumab) injection, for subcutaneous use.
  2. NIASPAN® (niacin extended-release tablets).
  3. JUXTAPID (lomitapide) capsules, for oral use.
  4. Banach M. Lipoprotein (a)—We Know So Much Yet Still Have Much to Learn …. JAHA. 2016; 5 (4): p.e003597. doi: 10.1161/jaha.116.003597 . | Open in Read by QxMD
  5. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary. J Am Coll Cardiol. 2019; 73 (24): p.3168-3209. doi: 10.1016/j.jacc.2018.11.002 . | Open in Read by QxMD
  6. Fernández-Ruiz I. No effect of PCSK9 inhibitors on cognitive function. Nature Reviews Cardiology. 2017; 14 (10): p.568-568. doi: 10.1038/nrcardio.2017.134 . | Open in Read by QxMD