- Pharmshala

Anti-Hyperlipidemic Drugs

Lipoprotein biology and the drug classes — statins, fibrates, ezetimibe, PCSK9 inhibitors and more — used to manage cholesterol and triglycerides.

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Lipoproteins and why they matter

Cholesterol and triglycerides travel in the blood packaged into lipoproteins. LDL (“bad” cholesterol) deposits cholesterol into arterial walls and drives atherosclerosis; HDL (“good” cholesterol) carries cholesterol back to the liver for disposal (reverse transport); triglyceride-rich VLDL is also linked to cardiovascular risk. Anti-hyperlipidemic drugs aim to lower LDL and triglycerides and, in some cases, raise HDL.

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Statins (HMG-CoA reductase inhibitors)

e.g. atorvastatin, rosuvastatin, simvastatin. The first-choice drug class for lowering LDL.

Statins block HMG-CoA reductase, the rate-limiting enzyme of hepatic cholesterol synthesis; the liver responds by expressing more LDL receptors, clearing more LDL from the blood.

Effect: Reduce LDL by roughly 20–50% depending on dose/agent; modestly lower triglycerides and raise HDL.
Other benefits: “Pleiotropic” effects independent of lipid lowering are described — plaque stabilisation and anti-inflammatory effects — contributing to the strong cardiovascular outcome benefits seen in trials.
Adverse effects: Myalgia/myopathy (rarely progressing to rhabdomyolysis), and a small rise in liver transaminases; liver function is monitored.

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Other lipid-lowering drug classes

Class	Examples	Mechanism	Main effect
Fibrates	Fenofibrate, gemfibrozil	Activate PPAR-α, raising lipoprotein lipase activity	Mainly lower triglycerides (VLDL clearance); modest HDL rise
Bile acid sequestrants	Cholestyramine, colestipol	Bind bile acids in the gut, preventing their reabsorption; the liver uses more cholesterol to make new bile acids, upregulating LDL receptors	Lower LDL; older agents, GI side effects limit use
Cholesterol absorption inhibitor	Ezetimibe	Blocks the NPC1L1 transporter in the intestinal brush border, reducing dietary and biliary cholesterol absorption	Modest LDL lowering alone; often added to a statin
PCSK9 inhibitors	Evolocumab, alirocumab (injectable monoclonal antibodies)	Block PCSK9, the protein that normally marks LDL receptors for degradation — more LDL receptors survive on the liver surface	Substantial additional LDL lowering; used when statins are insufficient or not tolerated
Nicotinic acid (niacin)	Niacin	Reduces hepatic VLDL synthesis	Lowers triglycerides and LDL, raises HDL; flushing is a common side effect and limits use
Omega-3 fatty acids	Fish oil / icosapent ethyl	Reduce hepatic triglyceride synthesis	Used mainly for marked hypertriglyceridaemia