Heart disease patients taking the PCSK9 inhibitor alirocumab to achieve very low levels of cholesterol may not experience an increase in adverse events, including memory impairment or nervous system disorders, but may have an increased risk of cataracts, according to a study published Jan. 30 in the Journal of the American College of Cardiology.

Jennifer G. Robinson, MD, MPH, and colleagues pooled data from 14 randomized, controlled studies that included 5,234 patients treated with alirocumab for up to two years. They looked for the occurrence of adverse events in patients who achieved two or more consecutive LDL cholesterol values of less than 25 mg/dL or less than 15 mg/dL.

Results showed that the overall incidence of adverse events was similar in patients taking alirocumab versus those taking a placebo, including musculoskeletal events, neurologic conditions, neurocognitive events (including memory), renal events or liver events. There was not an increased incidence of diabetes, despite previous studies showing an excess of diabetes in patients with LDL cholesterol lower than 30mg/dL on statin therapy. There was an increased incidence of cataracts in patients with LDL less than 25 versus greater than 25. The authors explain that this could be a chance finding, or it could be because reducing cholesterol accelerates underlying aging-related changes, contributing to cataracts.

“The safety of these new drugs is critical to patients who have no other means by which to control their life-threatening high cholesterol,” said Robinson. “The long-term effects of very low levels of LDL cholesterol are under evaluation in ongoing large clinical trials.”

In a related editorial comment, Brendan M. Everett, MD, FACC, adds that “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.”

“We expect two very large endpoint trials to be presented at ACC.17 in March,” said Kim A. Eagle, MD, MACC, editor-in-chief of ACC.org.

Keywords: Antibodies, Monoclonal, Cataract, Cholesterol, Cholesterol, LDL, Diabetes Mellitus, Heart Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Incidence, Liver, Nervous System Diseases

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