The potential risk of lowering LDL-C to very low levels (<40 mg/dL) has not been confirmed and its association with conditions like cancer, hemorrhagic stroke, depression, preterm birth, etc. are still under debate as evidences are lacking. It is said that good health may co-exist with prolonged exposure to very low LDL-C levels. Umbilical cord measurements suggest that fetal growth and development occur in the setting of LDL-C <40 mg/dL. Investigators at Brigham and Women’s Hospital have shown that PCSK9 inhibitor (evolocumab) when added to statin can lower LDL-C level even to <10 mg/dL, which safely causes additional lowering of CV events without much side effects.

In the recently published FOURIER trial (total 25,982 patients), where again evolocumab has been used for progressive lowering of LDL-C, 10% patients achieved LDL-C level <0.5 mmol/L (20 mg/dL), 31% patients achieved LDL-C level 0.5 mmol/L to <1.3 mmol/L, which showed that there is a monotonic relationship between achieved LDL-C level and major CV outcomes down to LDL-C <0.2 mmol/L and there was no safety concerns over a median period of 2.2 years. Very low LDL-C also did not have a negative impact on cognition, reaction time or memory. So in future, our guidelines may suggest a further lowering of LDL-C goal.