Which medications in the drug class PCSK9 Inhibitors are used in the treatment of Myocardial Infarction?

Updated: May 07, 2019
  • Author: A Maziar Zafari, MD, PhD, FACC, FAHA; Chief Editor: Eric H Yang, MD  more...
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Answer

PCSK9 Inhibitors

Over the last decade, inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising target to reduce residual cardiovascular disease risk. PCSK9 is a protein that binds to low-density lipoprotein (LDL) receptors (LDLR) to promote their degradation. Monoclonal antibodies inhibit PCSK9 and thus prevent LDLR degradation. This action will increase the number of LDLRs and subsequently increase the clearance of LDL, ultimately lowering LDL-C levels. 

In December 2017, the FDA approved the first PCSK9 inhibitor, evolocumab (Repatha), for the prevention of strokes, heart attacks, and coronary revascularizations. [64] The approval was based on data from the evolocumab cardiovascular outcomes study (FOURIER). In the FOURIER clinical trial, evolocumab demonstrated significant benefits for 27,564 patients with established cardiovascular disease. The study revealed that when used in addition to optimized statin therapy, evolocumab reduced the risk of heart attack by 27%, the risk of stroke by 21%, and the risk of coronary revascularization by 22%. In addition, evolocumab showed a statistically significant 15% reduction in the risk of the primary composite endpoint, which included hospitalization for unstable angina, coronary revascularization, heart attack, stroke, or cardiovascular death. [65]

In April 2019, the FDA expanded the indication for alirocumab (Praluent) to include risk reduction of MI, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease. [135] Approval was based on the ODYSSEY OUTCOMES trial (N=18,924) in patients with elevated LDL-C despite treatment with maximally tolerated statins. Patients who received injections of alirocumab 75 mg or 150 mg every other week achieved reduction in the risk for major cardiovascular events by 15% and all-cause death by 15% at a median follow-up of 2.8 years compared with those who received placebo. [136]

Evolocumab (Repatha)

Human monoclonal IgG2 directed against PCSK9. Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the LDLR, preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels. 

Alirocumab (Praluent)

Monoclonal antibody that binds to PCSK9. LDL-C is cleared from the circulation preferentially through the LDL receptor (LDLR) pathway. PCSK9 is a serine protease that destroys LDLR in the liver, resulting in decreased LDL-C clearance and increased plasma LDL-C.


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