PCSK9 Inhibitors and Cardiovascular Events

پنجمين كنگره بين المللي پيشگيري از بيماريهاي قلب و عروق

7 الي 9 مهر 1395، شيراز - ايران

Presentation Type: Speech

Importance: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were recently approved for lowering low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia (FH) or atherosclerotic cardiovascular disease (ASCVD) and have potential for broad ASCVD prevention.
The American College of Cardiology has updated their recommendations for the management of elevated LDL cholesterol levels in high-risk patients, specifically addressing the use of non-statin therapies, such as protein convertase subtilisin/kexin 9 (PCSK9) inhibitors and ezetimibe (Zetia, Merck/Schering-Plough), in patients unable to achieve sufficient LDL-cholesterol lowering PCSK9 is a protease that promotes degradation of LDL Receptors (LDLRs) in the liver, which leads to an increase in LDL.By blocking PCSK9 binding to LDLRs, SAR236533 is blocking degradation of LDLRs and consequently increasing the number of LDLRs molecules available to remove LDL-C (thus decreasing LDL-C levels).
Only after ezetimibe has been tried should physicians consider adding or replacing ezetimibe with one of the PSCK9 inhibitors, alirocumab (Praluent, Sanofi/Regeneron Pharmaceuticals) orevolocumab (Repatha, Amgen).
In the 2013, the American College of Cardiology/American Heart Association (ACC/AHA) shifted away from traditional LDL- and non-HDL–cholesterol targets and instead recommended statin therapy based on patient risk. As part of those guidelines, patients who fell into one of four patient groups were eligible for statin therapy, with the goal to achieve at least a 50% reduction in LDL cholesterol levels with a high-intensity statin for those with atherosclerotic cardiovascular disease or those with a baseline LDL-cholesterol level ≥ 190 mg/dL. Others were recommended a moderate-dose statin to achieve a 30% to 50% reduction in LDL cholesterol levels.
For high-risk patients with clinical atherosclerotic cardiovascular disease, the updated ACC consensus document recommends ezetimibe first if the patient fails to achieve at least a 50% reduction in LDL cholesterol. If adding ezetimibe doesn’t achieve that goal, evolocumab or alirocumab can either be added or used to replace ezetimibe. For the patient with clinical atherosclerotic cardiovascular disease and a baseline LDL-cholesterol ≥ 190 mg/dL not due to secondary causes, a bile-acid sequestrant can also be considered as second-line therapy before adding the PCSK9 inhibitor.
In primary prevention, the ACC states ezetimibe can be considered for patients without existing cardiovascular disease who have a baseline LDL cholesterol level ≥190 mg/dL and who are unable to achieve the desired reduction in LDL cholesterol levels. In addition, a bile-acid sequestrant can also be considered as second-line therapy. If those two options fail, PCSK9 inhibition can be used as treatment.

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