Key result
Targeting LDL-C of 40-50 mg/dL provides cardiovascular benefits safely without increasing adverse events.
Why the study?
The lower limit of LDL-C that offers cardiovascular benefits without safety concerns remains debated, necessitating a review of safety data from major lipid-lowering studies.
Supports very low LDL-C targets clinically; leaves open need for dedicated prospective confirmation.
BACKGROUND: Low-density Lipoprotein Cholesterol (LDL-C) is a major Cardiovascular (CV) risk factor. Accumulating evidence supports a linear association between LDL-C levels and CV risk. However, the lower limit of LDL-C that might offer CV benefits without any safety concerns is still a topic of debate. OBJECTIVE: The purpose of this review is to present the safety of reducing LDL-C to low levels as it comes from major lipid-lowering drug studies, and to discuss data on several safety events that have been associated with low LDL-C levels. METHODS: A comprehensive literature search was performed to identify available data from clinical studies evaluating the association of low LDL-C with safety outcomes. RESULTS: Several large trials have evaluated the safety or reducing LDL-C to levels lower than 50 mg/dl or even lower than 25 mg/dl, more commonly with the use of a combination of statins with ezetimibe or proprotein convertase subtilisin kexin 9 inhibitors. In almost all trials, CV benefits were observed with LDL-C levels of 50 mg/dl or less compared with higher levels. In terms of safety, reduction of LDL-C to such levels was not associated with any significant adverse event. Of importance, cancer and hemorrhagic stroke incidences were not increased in patients attaining LDL-C lower than 40-50 mg/dl. Data regarding the impact of lowering LDL-C with neurocognitive disorders are contradictory; nevertheless, most studies stand in favor of neurocognitive safety with LDL-C reductions to low levels. CONCLUSION: Achieving an LDL-C of 40-50 mg/dl seems to be safe, and importantly might offer CV beneficial effects. Data for attaining levels below 25 mg/dl is limited, however in favor of such reductions.
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Faselis et al. (2018) conducted a review in Dyslipidemia and Cardiovascular Risk. Reduction of LDL-C to very low levels (<50 mg/dL) and multidimensional lipid assessment vs. Higher LDL-C levels and traditional lipid panels was evaluated. Achieving very low LDL-C levels of 40-50 mg/dL is safe and provides cardiovascular benefits without increasing the risk of cancer, hemorrhagic stroke, or neurocognitive disorders.
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