Repatha 140 mg
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These studies suggest Evolocumab (Repatha) 140 mg is effective in significantly reducing LDL-C levels and is valuable for treating various forms of hypercholesterolemia, especially in patients who cannot achieve LDL-C goals with statins alone.
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Evolocumab (Repatha®) 140 mg: A Potent Cholesterol-Lowering Therapy
Introduction to Evolocumab (Repatha®)
Evolocumab, marketed under the trade name Repatha®, is a fully human monoclonal antibody that targets proprotein convertase subtilisin/kexin type 9 (PCSK9). This medication is administered subcutaneously at a dosage of 140 mg every two weeks or 420 mg once monthly .
Mechanism of Action: PCSK9 Inhibition
PCSK9 is an enzyme secreted by the liver that plays a crucial role in the turnover of low-density lipoprotein receptors (LDL-R). By binding to the extracellular part of LDL-R, PCSK9 leads to its degradation in the lysosome rather than recycling it to the cell surface. This process reduces the number of LDL-R on the cell surface, thereby decreasing LDL-C uptake and increasing LDL-C levels in the bloodstream. Evolocumab works by inhibiting PCSK9, preventing its interaction with LDL-R, and thus significantly reducing LDL-C levels.
Clinical Efficacy in Hyperlipidemia
Primary Hypercholesterolemia and Mixed Dyslipidemia
In multiple 12-week phase III trials, evolocumab demonstrated superior efficacy in reducing LDL-C levels compared to placebo and ezetimibe. The treatment differences ranged from -54.8% to -76.3% versus placebo and -36.9% to -47.2% versus ezetimibe. This efficacy was observed in various patient groups, including those on statin therapy, statin-intolerant patients, and those receiving evolocumab as monotherapy.
Familial Hypercholesterolemia
Evolocumab has also shown significant efficacy in patients with heterozygous familial hypercholesterolemia (HFe) and homozygous familial hypercholesterolemia (HFo). In HFe patients, evolocumab reduced LDL-C levels when added to statins with or without other lipid-lowering drugs. In HFo patients, a 12-week phase III trial reported a treatment difference of approximately 30% versus placebo when evolocumab was added to statins with or without ezetimibe.
Long-Term Efficacy and Safety
The long-term efficacy of evolocumab has been maintained, and it has been well tolerated across various studies. Evolocumab not only reduces LDL-C but also significantly lowers total cholesterol, non-HDL cholesterol, apoprotein B, and lipoprotein(a). Safety profiles indicate good tolerance, making it a viable option for patients who cannot achieve LDL-C goals with statins alone or who are statin-intolerant .
Conclusion
Evolocumab (Repatha®) at a dosage of 140 mg every two weeks is a highly effective and well-tolerated treatment for reducing LDL-C levels in patients with primary hypercholesterolemia, mixed dyslipidemia, and familial hypercholesterolemia. Its ability to inhibit PCSK9 and thereby enhance LDL-R recycling makes it a valuable addition to lipid-lowering therapies, particularly for patients who struggle to meet LDL-C targets with traditional treatments.
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