Extremely low LDLc not associated with serious side effects with PCSK9 therapy

Journal of Clinical Lipidology (2018) 12, 292–299 original

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Highlights

Many patients on proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors achieve extremely low low-density lipoprotein cholesterol (LDL-C) levels.

Extremely low LDL-C levels are associated with even less cardiovascular risk.

Extremely low LDL-C concentrations cause no clinically relevant side effects.Low LDL-C levels due to higher clearance are a marker of adequate LDL–LDLreceptor function.

Conclusion

In conclusion, the clinical and physiological evidence makes the case that extremely low LDL-C plasma concentrations mediated by increased LDLR activity are not associated with significant adverse effects, within the limitations of the available clinical trial data.

Given that the main function of LDL metabolism is cholesterol excretion, therapies that increase LDLR activity could provide optimization of this physiological role.

In other words, extremely low LDL-C concentrations due to increased receptor-mediated clearance should be interpreted as a marker of adequate LDL-LDLR pathway function.