What if my LDL is very low?

SUMMARY AND COMMENT | LIPID MANAGEMENT February 23, 2017 Are Very Low LDL Cholesterol Levels Safe? Kirsten E. Fleischmann, MD, MPH Reviewing  Everett BM., J Am Coll Cardiol 2017 Feb 7; 69:483 Cataracts and adverse neurocognitive events might be more common with very low LDL cholesterol levels.

The proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitors (evolocumab [Repatha] and alirocumab [Praluent]) are potent lipid-lowering agents that can result in very low levels of LDL cholesterol. But can LDL cholesterol be driven so low that adverse events ensue? In two meta-analyses, researchers explore this possibility. In an industry-sponsored analysis, data from 14 trials in which alirocumab was added to background lipid-lowering therapy were pooled. Treatment duration ranged from 8 to 104 weeks. Among 3340 alirocumab patients, 25% had two consecutive LDL cholesterol measurements <25 0.8="" 9="" achieved="" adverse="" alirocumab="" analyses="" analysis="" and="" any="" as="" at="" baseline="" but="" cataract="" cataracts="" cholesterol="" complications="" control="" diabetes="" different="" dl.="" dl="" effects="" event="" events="" for="" groups.="" higher="" in="" incidence="" incident="" its="" ldl="" levels="" low="" mg="" neurocognitive="" neurological="" not="" of="" or="" overall="" p="" patients="" presented.="" propensity-adjusted="" propensity="" rates="" reported="" significantly="" similar="" specific="" such="" than="" the="" those="" very="" vs.="" was="" were="" with="" without=""> A second meta-analysis, which was limited to studies with at least 6 months of follow-up, also showed no significant difference in serious adverse events; however, subgroup analysis of the larger outcome studies suggested excess incidence of neurocognitive adverse events in the very low cholesterol group (odds ratio, 2.85), although the overall incidence was low (<1 p=""> Comment In the first analysis, very low LDL cholesterol levels weren't associated with excess adverse events, except for a higher incidence of cataracts. (This finding has biological plausibility — an editorialist reminds us that the lens of the eye synthesizes cholesterol for structure and clarity.) The second analysis suggests excess neurocognitive adverse events in subgroup analysis only, but a low incidence overall, and authors note that the type and severity of these adverse events are unknown. Although these results are generally reassuring, longer-term monitoring and structured assessment of neurocognitive adverse events will be needed before the safety of very low LDL cholesterol levels with PCSK-9 inhibitors can be assessed fully.