Ezetimibe and PCSK-9 Inhibitors – Cholesterol Test Prep and Practice Pearls

In this pharmacology podcast episode, we focus on two key non-statin cholesterol-lowering therapies: ezetimibe and PCSK9 inhibitors (Click here to listen to the statin podcast episode). These agents play a role in lipid management, particularly for patients who are unable to reach LDL cholesterol goals with statins alone or who have statin intolerance.

Ezetimibe works by inhibiting the absorption of dietary and biliary cholesterol at the brush border of the small intestine. By reducing the amount of cholesterol delivered to the liver, ezetimibe lowers circulating LDL cholesterol by approximately 15 to 25 percent. It is taken orally once daily and is commonly used as add-on therapy to statins in patients with established atherosclerotic cardiovascular disease or high baseline LDL levels. Ezetimibe is generally well tolerated, with a favorable safety profile and minimal systemic exposure, making it an attractive option in older adults and patients with multiple comorbidities.

PCSK9 inhibitors, including alirocumab and evolocumab, offer a much more potent LDL-lowering effect. These monoclonal antibodies work by blocking PCSK9, a protein that promotes degradation of LDL receptors in the liver. By preserving LDL receptors, PCSK9 inhibitors enhance clearance of LDL cholesterol from the bloodstream, often reducing LDL levels by 50 to 60 percent. They are administered via subcutaneous injection every two to four weeks and are most commonly used in patients with familial hypercholesterolemia, established cardiovascular disease, or persistently elevated LDL despite maximally tolerated statin and ezetimibe therapy.

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