Abstract
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.
Keywords: Low-density lipoprotein cholesterol, safety, statins, PCSK9 inhibitors, cardiovascular disease, cancer.
Current Pharmaceutical Design
Title:Is very low LDL-C harmful?
Volume: 24 Issue: 31
Author(s): Charles Faselis*, Konstantinos Imprialos, Haris Grassos, Andreas Pittaras, Manolis Kallistratos and Athanasios Manolis
Affiliation:
- VA Medical Center and George Washington University, Washington, DC,United States
Keywords: Low-density lipoprotein cholesterol, safety, statins, PCSK9 inhibitors, cardiovascular disease, cancer.
Abstract: 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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Cite this article as:
Faselis Charles *, Imprialos Konstantinos , Grassos Haris , Pittaras Andreas , Kallistratos Manolis and Manolis Athanasios , Is very low LDL-C harmful?, Current Pharmaceutical Design 2018; 24 (31) . https://dx.doi.org/10.2174/1381612824666181008110643
DOI https://dx.doi.org/10.2174/1381612824666181008110643 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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