Study: Very Low LDL-C Achieved with PCSK9 Inhibitors Not Associated with Increased Adverse Events

Very low LDL-C levels achieved through the use of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor were not associated with an increased risk for treatment-related adverse events in patients taking alirocumab for 18 months, according to a new study.

Researched pooled data from 14 double-blind randomized control trials that included 5234 participants, 3340 of which were treated with alirocumab and 1894 of which were treated with placebo or ezetimibe. Total treatment time for the trials ranged from 8 to 104 weeks, and the median treatment exposure was 78 weeks.
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A total of 839 (25.1%) patients had 2 consecutive LDL-C levels below 25 mg/dl, and 314 (9.4%) patients had LDL-C levels below 15 mg/dl. Participants with LDL-C levels below 25 mg/dl had lower baseline LDL-C than participants with LDL-C levels at or above 25 mg/dl.

Overall, rates for adverse events were similar between patients with LDL-C levels below 25 mg/dl and below 15 mg/dl, and in patients with LDL levels at or above 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. No difference in rates of [treatment-emergent adverse events] related to diabetes mellitus was observed when controlling for baseline characteristics predictive of achieving LDL-C <25 mg/dl,” the researchers wrote.

The rate of cataracts was higher in patients with LDL-C below 25 mg/dl compared to participants with LDL-C at or above 25 mg/dl when researchers performed a propensity analysis. However, there were no observed differences in incidences of cataracts between the pooled alirocumab and control groups.

“Although the consequences of very low LDL-C were not identified in these trials, the long-term effects of very low levels of LDL-C are unknown. Data from large, ongoing cardiovascular outcomes trials should provide important information on the cardiovascular event reduction benefits and adverse effects of long-term exposure to pharmacologically induced low LDL-C levels,” the researchers concluded.

—Melissa Weiss

Reference:

Robinson JG, Rosenson RS, Farnier M, et al. Safety of very low low-density lipoprotein cholesterol levels with alirocumab [published online before print January 30, 2017]. Journal of the American College of Cardiology. doi:10.1016/j.jacc.2016.11.037.