Statins are the first-line therapy for lowering LDL-C and total cholesterol levels. Statins work by inhibiting HMG-CoA reductase, a liver enzyme involved in cholesterol synthesis. This inhibition leads to upregulation of LDL receptors in the liver, enhancing clearance of LDL from the blood. Some commonly prescribed statins include atorvastatin, rosuvastatin, simvastatin, and pravastatin. Statins are generally well-tolerated but can cause mild side effects like muscle pain. Rarely, they may cause myopathy. When initiating statin therapy, it is important to monitor liver function tests and be aware of any muscle symptoms. Guidelines recommend adding ezetimibe or PCSK9 inhibitors for additional LDL lowering in very high-risk patients who are unable to reach LDL goals with maximally tolerated statin dose alone.

Fibrates

Fibrates primarily target elevated triglyceride levels. They work by activating PPAR-alpha nuclear receptors, which in turn modulate fatty acid and lipoprotein metabolism. Common fibrates include gemfibrozil and fenofibrate. While fibrates can provide 20-50% reduction in triglyceride levels, they have little effect on lowering Antihyperlipidemic Drugs may actually increase it slightly. Hence, fibrates are primarily used as an adjunct to statins in patients with severe hypertriglyceridemia >500 mg/dL to help prevent pancreatitis. Fibrates are generally well-tolerated but can cause gastrointestinal side effects and occasionally raise liver enzymes or creatinine levels.

Niacin

Niacin, or vitamin B3, is one of the most effective drugs for raising HDL-C levels and moderately lowering LDL-C and triglyceride levels when used at high extended-release doses. It works through multiple mechanisms such as inhibiting lipolysis and free fatty acid flux to the liver. However, clinical trials with niacin have failed to show reduction in cardiovascular outcomes when added to statin therapy, most likely due to compliance issues from flushing side effects. Hence, niacin is no longer recommended as a antihyperlipidemic drugs but may have a role as an adjunct in patients who do not tolerate other options and require additional HDL-C and triglyceride lowering.

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