Emerging Therapeutic Approaches to Treat Dyslipidemia
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Statins are safe, efficacious and the cornerstone of cardiovascular disease prevention strategies. A number of add-on therapies with complementary actions on the plasma lipid profile have been tested in large scale trials to see if they give incremental benefit. In particular, the ‘HDL hypothesis’ – that raising this lipoprotein will promote reverse cholesterol transport and reduce cardiovascular risk – has been examined using drugs such as dalcetrapib and niacin. So far, results have been negative, and this has raised questions over the nature of the association of HDL with atherosclerosis, and whether statins reduce cardiovascular risk through multiple mechanisms. There is still an unmet clinical need especially in those patients who cannot tolerate statins and those with severe hyperlipidemia, and so new therapeutic approaches have been developed. These show significant promise in terms of LDL-cholesterol lowering but significant challenges include cost, route of administration (subcutaneous injection) and side effects. Testing in major outcome trials will be required to demonstrate their clinical utility.
KeywordsCardiovascular disease Dyslipidemia Hypercholesterolemia LDL-cholesterol Antisense oligonucleotide therapy Microsomal transfer protein inhibition PCSK9 inhibition CETP inhibition
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Conflict of Interest
David Preiss reports participating on an advisory board for Sanofi (outside the submitted work); and involvement in the planning and/or conduct of current trials of lipid modifying agents sponsored by Amgen and Pfizer.
Chris J. Packard reports receiving grants and personal fees from Roche, personal fees from MSD and personal fees from AstraZeneca, outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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