PubMed · 12480449
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P N Durrington, MRC/BHF Heart Protection Study. 2002-11-30. MRC/BHF Heart Protection Study.. https://doi.org/10.1016/s0140-6736(02)11688-6
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Proprotein convertase subtilisin-like kexin type 9 (PCSK9) is a newly discovered serine protease that destroys low density lipoprotein (LDL) receptors in liver and thereby controls the level of LDL in plasma. Mutations that increase PCSK9 activity cause hypercholesterolemia and coronary heart disease (CHD); mutations that inactivate PCSK9 have the opposite effect, lowering LDL levels and reducing CHD. Although the mechanism of PCSK9 action is not yet clear, the protease provides a new therapeutic target to lower plasma levels of LDL and prevent CHD.
Statins are normally administered for the treatment of dyslipidemia on a daily basis. This standard dosing regimen is well tolerated by most patients. Occasionally, patients discontinue therapy secondary to side effects, most commonly myalgias. We describe 2 patients who were unable to tolerate daily atorvastatin therapy secondary to myalgias and were subsequently treated with rosuvastatin administered on Mondays, Wednesdays, and Fridays, with resolution of adverse effects. Significant reductions in serum low-density lipoprotein cholesterol levels were observed in the 2 patients despite the alternate-day dosing regimen. Rosuvastatin was chosen because of its long half-life (19 hours) and very high potency.
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