Recent Developments in the Treatment of Familial Hypercholesterolemia: A Review of Several New Drug Classes
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Prevention (L Sperling, Section Editor)
Recent Developments in the Treatment of Familial Hypercholesterolemia: A Review of Several New Drug Classes Michael J. Wilkinson, MD Michael H. Davidson, MD* Address *Department of Medicine, University of Chicago Medicine, 150 E. Huron Street, Suite 900, Chicago, IL 60611, USA Email: [email protected]
Published online: 13 November 2013 * Springer Science+Business Media New York 2013
Keywords Familial hypercholesterolemia I Hyperlipidemia I Low-density lipoprotein cholesterol (LDL-C) I Prevention I Lipidology I Microsomal trigylceride transfer protein (MTP) inhibitor I Apolipoprotein B synthesis inhibitior I Cholesterol ester transfer protein (CETP) inhibitor I Pro-protein convertase subtilisin/kexin 9 (PCSK9) inhibitor
Opinion statement Familial hypercholesterolemia is a genetic disorder of the low-density lipoprotein cholesterol (LDL-c) receptor leading to severe elevations in plasma levels of LDL-c which results in premature atherosclerosis and cardiovascular events. Statins, ezetimibe, and bile acid sequestrants significantly lower LDL-c levels in these patients and subsequently markedly improve survival; however, even with these interventions LDL-c goals often are not met. Several new drug classes are in development and have the potential to make reaching these cholesterol goals easier. In this article we review the most recent trials of several classes of drugs with the potential to change the future of familial hypercholesterolemia management: microsomal triglyceride transfer protein (MTP) inhibitors, apolipoprotein B synthesis inhibitors (mipomersen), cholesterol ester transfer protein (CETP) inhibitors and inhibitors of pro-protein convertase subtilisin/kexin 9 (PCSK9). Each class has shown promise with regard to their effects on the lipid profile. However, the potential side-effects of each drug are also being determined and have limited the development of certain agents. Therefore, the long-term effects of these drug classes, both in terms of side-effects and their effect on clinical outcomes such as cardiovascular events and mortality, continue to be determined.
Introduction Familial hypercholesterolemia (FH) is an autosomal dominant disorder, either heterozygous or homozy-
gous, that results from defects in genes associated with lipid metabolism. The mutations of the low-density li-
Recent Developments in the Treatment of Familial Hypercholesterolemia Wilkinson and Davidson poprotein cholesterol (LDL-c) receptor that lead to the development of familial hypercholesterolemia are diverse and impact the severity of the disease. The disease is characterized by premature atherosclerosis and associated events, such as premature coronary artery disease and myocardial ischemia (Figure 1). Patients with familial hypercholesterolemia are generally not adequately responsive to diet and lifestyle modification, and therefore statins represent the backbone of pharmacotherapy. Other lipid-lowering agents, such as bile-acid sequestrants and ezetimibe, have also been used
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