Physicians' Academy for Cardiovascular Education

Few adverse events of very low LDL-C levels with PCSK9 antibody

Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab: Pooled Data From Randomized Trials

Literature - Robinson JG, Rosenson RS, Farnier M, et al. - J Am Coll Cardiol. 2017;69(5):471-482

Main results

Conclusion

In a study of more than 5 000 patients with a median drug exposure of 1.5 years, low levels of LDL-C (<25 mg/dl) were well tolerated. Although the incidence of cataracts was similar between the overall alirocumab and overall control groups, there was an increased incidence of cataracts in those with LDL-C <25 mg/dl. There were no meaningful imbalances between groups in musculoskeletal and neurological conditions (including peripheral neuropathy), neurocognitive events (including those related to memory), and renal or hepatic events. The long-term effects of very low levels of LDL-C are unknown.

Editorial comment

In his editorial article [5], Everett BM discusses the three most important findings in the Robinson et al analysis:

  • the increased incidence of cataracts in patients with LDL-C <25 mg/dl is consistent with other studies and may be explained by the cholesterol demands of the ocular lens for the maintenance of the lens structure and clarity
  • the relationship of LDL-C-lowering therapy with diabetic-related complications in patients with diabetes at baseline and LDL-C <25 mg/dl
  • the fact that although in this analysis the neurocognitive adverse effects did not differ between patients with LDL-C<25 mg/dl and higher LDL-C levels, in the original study, the neurocognitive adverse effects rates were higher in the alirocumab group compared with the placebo group

The author concludes: ‘The data from the ODYSSEY program represent an important first step in understanding the risks of achieving very low LDL-C concentrations with this novel class of medications.’…. ‘In that context, the data presented here, although reassuring, represent only the beginning of our understanding of the safety of this novel class of medications. The ongoing cardiovascular endpoint trials of alirocumab should provide not only a sense of the true cardiovascular benefit of these drugs but also a more accurate and nuanced understanding of their risks.’

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