What is the role of alirocumab (Praluent) in the lowering of low-density lipoprotein cholesterol (LDLc) levels?

Updated: Apr 09, 2021
  • Author: Nainesh K Gandhi, MD, MSE; Chief Editor: Keith K Vaux, MD  more...
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The first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor approved in the United States was alirocumab (Praluent) in July 2015. It is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease who require additional lowering of LDLc. [16]

Alirocumab’s approval was based on data from the pivotal phase III ODYSSEY program, which showed consistent, positive results for alirocumab compared to placebo and included current standard-of-care therapy (statins). The ODYSSEY LONG TERM trial evaluated alirocumab 150 mg SC every 2 weeks. Alirocumab reduced LDLc by 58%, as compared to placebo at week 24, when added to current standard of care, including maximally tolerated statins. [17] In ODYSSEY COMBO I, alirocumab 75 mg every 2 weeks as an adjunct to statins reduced LDLc by an additional 45% when compared to placebo at week 12. [18] At week 24 in the same trial, alirocumab reduced LDLc by an additional 44% compared to placebo. In this study, if additional LDLc lowering was required based on prespecified criteria at week 8, alirocumab was up-titrated to 150 mg at week 12 for the remainder of the trial. Eighty-three percent of patients remained on their initial 75-mg dose.

The ODYSSEY OUTCOMES trial showed that use of alirocumab significantly reduces ischemic events, including all-cause mortality and myocardial infarction (MI), as compared to placebo, in patients with an acute coronary syndrome (ACS) event within the preceding 1 to 12 months. [19, 20]  In patients with diabetes, after a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0.65-1.30 mmol/L produced about twice the absolute reduction in cardiovascular events as in those without diabetes. [21, 22]  Some studies of statin therapy have shown a slightly increased risk of type 2 diabetes. [23, 24, 25]  

In April 2021, alirocumab gained FDA approval as an adjunct to other LDL-C–lowering therapies for HoFH. Approval was based on the ODYSSEY HoFH trial (N = 69). Mean baseline LDL-C was 259.6 mg/dL in the placebo group and 295 mg/dL in the alirocumab group. At week 12, the least squares mean difference in LDL-C percent change from baseline was −35.6% (alirocumab [−26.9%] vs. placebo [8.6%]; P< 0.0001). [26]  

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