Nrcar interactive dyslipidaemia_poster

1
Triglyceride Cholesterol MTTP mutations Abetalipoproteinaemia Levels of ApoB-containing lipoproteins (200100, 157147) NPC1L1 Jejunum Terminal ileum Bile acids Bile acids LDL receptor LDL Plasma space MTP SR-B1 Acetate HMG-CoA reductase LRP1 LDL-receptor recycling 7α-hydroxylase FATPs Enterohepatic circulation ApoA-I ABCG1 ABCA1 Free cholesterol Cholesterol ester Cholesterol pool Extrahepatic tissue SR-B1 LCAT Statins reduce the plasma LDL-cholesterol level by as much as 55%. These drugs inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. The resulting reduction in cellular cholesterol content leads to compensatory upregulation of LDL receptors and increased uptake of LDL cholesterol by cells. A meta-analysis of 26 clinical trials (n = 169,138) showed that for every 1.0 mmol/l (40 mg/dl) reduction in LDL-cholesterol level with a statin, the risk of a major cardiovascular event is reduced by about one-fifth. 3 ApoB antisense oligonucleotides reduce the levels of apoB, LDL cholesterol, and non-HDL cholesterol by 25–30%. These compounds are short, synthetic analogues of natural nucleic acids that bind to mRNA, inhibit the synthesis of apoB and, therefore, decrease the secretion of apoB-containing lipoproteins. Whether apoB antisense oligonucleotides reduce the risk of cardiovascular events has not been tested in clinical trials, but one member of this class, mipomersen, has been approved by the FDA as an orphan drug for patients with homozygous familial hypercholesterolaemia. 4 PCSK9 inhibitors decrease the LDL-cholesterol level by 40–70% when given either as monotherapy or in addition to a statin. PCSK9 binds to the LDL receptor and enhances its breakdown in lysosomes, reducing receptor recycling back to the surface. Therefore, inhibition of PCSK9 with, for example, monoclonal antibodies increases the expression of the LDL receptor, which results in an increased uptake of LDL cholesterol into cells, primarily hepatocytes. PCSK9 is upregulated by statins, an effect that limits the LDL-cholesterol-lowering potential of these agents, which makes PCSK9 inhibition a rational adjunctive therapy to statins. Clinical trials to test the effects of PCSK9 monoclonal antibodies on cardiovascular events are ongoing. 5 Cholesterol-absorption inhibitors, such as ezetimibe, decrease the LDL-cholesterol level by about 18%, whether given as monotherapy or in addition to treatment with a statin. Ezetimibe reduces the absorption of cholesterol from the intestine by inhibiting NPC1L1. Reduced delivery of cholesterol to the liver increases hepatic LDL-receptor expression and, therefore, increases clearance of circulating LDL cholesterol. The use of ezetimibe to reduce the risk of cardiovascular events is being tested in the ongoing IMPROVE-IT trial. 6 Niacin decreases the plasma levels of triglyceride, LDL cholesterol, and proatherogenic lipoprotein(a) by 30–40%, 10–15%, and up to 30%, respectively, and increases the HDL-cholesterol level by 15–30%. The mechanism of action of niacin is not certain, but involves inhibition of adipose tissue lipolysis and hepatic triglyceride synthesis. As monotherapy, niacin reduces the rate of cardiovascular events. In combination with a statin, niacin promotes regression of atherosclerosis. However, in clinical trials involving patients optimally treated with statins, niacin did not reduce the rate of cardiovascular events. The future role of niacin is uncertain. 7 MTP inhibitors decrease the levels of apoB, and of VLDL and LDL cholesterol. Inhibition of MTP decreases the assembly of VLDL in the liver and, therefore, decreases the level of all apoB-containing lipoproteins. Whether MTP inhibitors reduce the rate of cardiovascular events has not been tested in clinical trials, but the MTP inhibitor lomitapide has been approved by the FDA for patients with homozygous familial hypercholesterolaemia. 8 Fibrates reduce the plasma triglyceride level by 30–50% and increase the HDL-cholesterol level by 2–20%, but have little effect on the LDL-cholesterol level. Fibrates activate peroxisome proliferator-activated receptor α, which stimulates the oxidation of free fatty acids in the liver, diverting them from triglyceride synthesis; induces expression of lipoprotein lipase, the enzyme responsible for hydrolysing plasma triglyceride; and inhibits synthesis of apoC-III, a protein that delays the catabolism of triglyceride-rich lipoproteins. The elevation in the HDL-cholesterol level might be caused by increased expression of the APOA1, APOA2, and ABCA1 genes. The results of trials involving fibrates have been variable, although fibrates have consistently produced a substantial reduction in the rate of cardiovascular events in individuals with hypertriglyceridaemia and a low HDL-cholesterol level. 9 CETP inhibitors increase the HDL-cholesterol level by up to 140%, decrease the LDL-cholesterol level by up to 35%, and lower the lipoprotein(a) level by >30%. CETP transfers cholesteryl esters from the HDL fraction, where it does not cause atherosclerosis, to the VLDL and LDL fractions, where it can cause atherosclerosis; inhibiting CETP is, therefore, potentially antiatherogenic. However, in a large, randomized trial, dalcetrapib had no effect on cardiovascular outcomes and, in another study, torcetrapib was associated with a significant 25% increase in major cardiovascular events, and a 58% increase in mortality. Large clinical trials are being conducted with anacetrapib and evacetrapib, which do not share the adverse effects of torcetrapib. 10 Bile-acid-sequestering resins reduce the LDL-cholesterol level by about 20%. Resins bind bile acids in the intestine and disrupt their enterohepatic circulation. The liver is stimulated to divert cholesterol into bile-acid synthesis, a process that reduces the cellular content of cholesterol, which leads to a compensatory upregulation of LDL receptors. In 1984, use of the bile-acid-sequestering agent cholestyramine was shown to reduce the LDL-cholesterol level and the risk of cardiovascular events. However, these agents have largely been superseded by newer drugs. 6 ApoB-100 ApoE ApoC-III ApoC-II ApoA-V ApoB-48 Chylomicron LPL Chylomicron remnant ApoB-48 ApoE ApoE LIPC LPL LDL CETP CETP inhibitors ApoA-I Endosome Nucleus Statins Triglyceride Cholesterol Fibrates MTP inhibitors LDLRAP1 Stomach PCSK9 LDLRAP1 Dietary fat Liver MTP ApoB-48 Duodenum ApoB antisense oligonucleotides ApoB-100 ApoB-100 ApoE Pre-βHDL HDL IDL VLDL Endosome Bile-acid-sequestering resins Cholesterol-absorption inhibitors VLDL Cholesterol Triglyceride Endosome LDLRAP1 mutations Autosomal-recessive hypercholesterolaemia LDL-cholesterol level (603813, 605747) LDLR mutations Familial hypercholesterolaemia LDL-cholesterol level (143890, 606945) ApoB-100 ApoB-100 PCSK9 gain-of-function mutations Autosomal-dominant hypercholesterolaemia LDL-cholesterol level (603776, 607786) PCSK9 loss-of-function mutations PCSK9 deficiency LDL-cholesterol level (607786) PCSK9 inhibitors Dietary and biliary sterol IBAT APOB ligand-binding mutations Familial defective apoB LDL-cholesterol level (144010, 107730) APOB structural mutations Hypobetalipoproteinaemia Levels of ApoB-containing lipoproteins (107730) ApoC-II ApoC-III ApoC-II ApoC-III Lysosome ApoB-containing lipoproteins PCSK9 Supplement to Nature Publishing Group journals REGENERON Dyslipidaemia and its treatment Robert A. Hegele and Philip Barter Disorders of plasma lipid and lipoprotein metabolism are well recognized as causative factors in the development of atherosclerotic cardiovascular disease. The rational management of such disorders requires an understanding of the factors that regulate plasma lipid metabolism and how abnormalities of such factors lead to dyslipidaemia. This poster displays the main lipid-metabolism pathways in the body, including synthesis in tissues and the interaction and transfer of lipids between the intestines, liver, blood, and peripheral tissues. The major classes of lipoproteins that transport lipids in blood plasma, and the factors involved in their assembly, interconversion, and catabolism are shown. Points at which monogenetic mutations affect protein concentration, function, and that lead (often in combination with lifestyle factors) to dyslipidaemia are identified. With this knowledge, therapeutic targets can be identified, and we can understand how existing lipid-modifying drugs as well as novel agents under development target these pathways, with the potential to correct the dyslipidaemia and reduce the risk of a major cardiovascular event. 1,2 Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York, USA, that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron markets medicines for eye diseases, colorectal cancer, and a rare inflammatory condition, and has product candidates in development in other areas of high unmet medical need, including hypercholesterolaemia, oncology, rheumatoid arthritis, allergic asthma, and atopic dermatitis. Sanofi, an integrated global health-care leader, discovers, develops, and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of health care with seven growth platforms: diabetes mellitus solutions, human vaccines, innovative drugs, consumer health care, emerging markets, animal health, and the new Genzyme. Since 2007, the Regeneron and Sanofi collaboration has been at the forefront of developing innovative new therapies that seek to address current unmet medical needs. The collaboration brings forth the best of both companies—technology, scientific expertise, commercial experience, and a focus on patient needs. Abbreviations ABCA1 ATP-binding cassette sub-family A member 1 ABCG1 ATP-binding cassette sub-family G member 1 Apo apolipoprotein CETP cholesteryl ester transfer protein FATPs fatty acid transport proteins HDL high-density lipoprotein HMG-CoA 3-hydroxy-3-methylglutaryl-coenzyme A IBAT ileal sodium/bile acid cotransporter IDL intermediate-density lipoprotein LCAT phosphatidylcholine-sterol acyltransferase LDL low-density lipoprotein LDLRAP1 low-density lipoprotein receptor adapter protein 1 LIPC hepatic triacylglyercerol lipase LPL lipoprotein lipase LRP1 low-density lipoprotein receptor-related protein 1 MTP microsomal triglyceride transfer protein NPC1L1 Niemann–Pick C1-like protein 1 PCSK9 proprotein convertase subtilisin/kexin type 9 SR-B1 scavenger receptor class B member 1 VLDL very-low-density lipoprotein Information on monogenic dyslipidaemias is formatted: Gene name | Clinical disorder Primary biochemical disturbance (OMIM® reference) References 1. Gotto, A. M. Jr & Moon, J. E. Pharmacotherapies for lipid modification: beyond the statins. Nat. Rev. Cardiol. 10, 560–570 (2013). 2. Watts, G. F., Ooi, E. M. M. & Chan, D. C. Demystifying the management of hypertriglyceridaemia. Nat. Rev. Cardiol. 10, 648–661 (2013). 3. Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376, 1670–1681 (2010). 4. Marais, A. D. & Blomm, D. J. Recent advances in the treatment of homozygous familial hypercholesterolaemia. Curr. Opin. Lipidol. 24, 288–294 (2013). 5. Petrides, F. et al. The promises of PCSK9 inhibition. Curr. Opin. Lipidol. 24, 307–312 (2013). 6. Couture, P. & Lamarche, B. Ezetimibe and bile acid sequestrants: impact on lipoprotein metabolism and beyond. Curr. Opin. Lipidol. 24, 227–232 (2013). 7. Lavigne, P. M. & Karas, R. H. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J. Am. Coll. Cardiol. 61, 440–446 (2013). 8. Cuchel, M. & Rader, D. J. Microsomal transfer protein inhibition in humans. Curr. Opin. Lipidol. 24, 246–250 (2013). 9. Jun, M. et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 375, 1875–1884 (2010). 10. Barter, P. J. & Rye, K. A. Cholesteryl ester transfer protein inhibition as a strategy to reduce cardiovascular risk. J. Lipid Res. 53, 1755–1766 (2012). Affiliations and competing interests Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 100 Perth Drive, London, ON N6A 5K8, Canada (R. A. Hegele). Centre for Vascular Research, Department of Medicine, University of New South Wales, High Street, Kensington, Sydney, NSW 2052, Australia (P. Barter). R. A. Hegele declares that he has received research support from Amgen and Merck; and received honoraria from, and is an advisory board member for, Aegerion, Amgen, Genzyme, Merck, and Valeant. P. Barter declares that he has received research support from Merck and Pfizer; honoraria from Amgen, AstraZeneca, Kowa, MSD, Novartis, Pfizer, and Roche; and is an advisory board member for AstraZeneca, CSL, Kowa, Lilly, Merck, Pfizer, and Roche. Edited by Gregory B. S. Lim; designed by Laura Marshall. The poster content is peer-reviewed and editorially independent. © 2013 Nature Publishing Group. http://www.nature.com/nrcardio/posters/dyslipidaemia/

Transcript of Nrcar interactive dyslipidaemia_poster

Triglyceride

Cholesterol

MTTP mutationsAbetalipoproteinaemia Levels of ApoB-containinglipoproteins (200100, 157147)

NPC1L1

Jejunum

Terminal ileum

Bile acids

Bile acids

LDL receptor LDL

Plasmaspace

MTP

SR-B1

Acetate

HMG-CoAreductase

LRP1

LDL-receptorrecycling

7α-hydroxylase

FATPs

Enterohepaticcirculation

ApoA-I

ABCG1

ABCA1

Freecholesterol

Cholesterolester

Cholesterol pool

Extrahepatictissue

SR-B1

LCAT

Statins reduce the plasma LDL-cholesterol level by as much as 55%. These drugs inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. The resulting reduction in cellular cholesterol content leads to compensatory upregulation of LDL receptors and increased uptake of LDL cholesterol bycells. A meta-analysis of 26 clinical trials (n = 169,138) showedthat for every 1.0 mmol/l (40 mg/dl) reduction in LDL-cholesterollevel with a statin, the risk of a major cardiovascular event isreduced by about one-�fth.3

ApoB antisense oligonucleotides reduce the levels of apoB, LDL cholesterol, and non-HDL cholesterol by 25–30%. These compounds are short, synthetic analogues of natural nucleic acids that bind to mRNA, inhibit the synthesis of apoB and, therefore, decrease the secretion of apoB-containing lipoproteins.Whether apoB antisense oligonucleotides reduce the risk ofcardiovascular events has not been tested in clinical trials, butone member of this class, mipomersen, has been approved bythe FDA as an orphan drug for patients with homozygous familialhypercholesterolaemia.4

PCSK9 inhibitors decrease the LDL-cholesterol level by 40–70% when given either as monotherapy or in addition to astatin. PCSK9 binds to the LDL receptor and enhances itsbreakdown in lysosomes, reducing receptor recycling back to thesurface. Therefore, inhibition of PCSK9 with, for example,monoclonal antibodies increases the expression of the LDL receptor, which results in an increased uptake of LDL cholesterol into cells, primarily hepatocytes. PCSK9 is upregulated by statins, an effect that limits the LDL-cholesterol-lowering potential of these agents, which makes PCSK9 inhibition a rational adjunctive therapy to statins. Clinical trials to test the effects of PCSK9 monoclonal antibodies on cardiovascular events are ongoing.5

Cholesterol-absorption inhibitors, such as ezetimibe,decrease the LDL-cholesterol level by about 18%, whether givenas monotherapy or in addition to treatment with a statin.Ezetimibe reduces the absorption of cholesterol from theintestine by inhibiting NPC1L1. Reduced delivery of cholesterolto the liver increases hepatic LDL-receptor expression and,therefore, increases clearance of circulating LDL cholesterol.The use of ezetimibe to reduce the risk of cardiovascular eventsis being tested in the ongoing IMPROVE-IT trial.6

Niacin decreases the plasma levels of triglyceride, LDL cholesterol, and proatherogenic lipoprotein(a) by 30–40%, 10–15%, and up to 30%, respectively, and increases the HDL-cholesterol level by 15–30%. The mechanism of action of niacin is not certain, but involves inhibition of adipose tissue lipolysis and hepatic triglyceride synthesis. As monotherapy, niacin reduces the rate of cardiovascular events. In combination with a statin, niacin promotes regression of atherosclerosis. However, in clinical trials involving patients optimally treated with statins, niacin did not reduce the rate of cardiovascular events. The future role of niacin is uncertain.7

MTP inhibitors decrease the levels of apoB, and of VLDL and LDL cholesterol. Inhibition ofMTP decreases the assembly of VLDL in the liver and, therefore, decreases the level of allapoB-containing lipoproteins. Whether MTP inhibitors reduce the rate of cardiovascular eventshas not been tested in clinical trials, but the MTP inhibitor lomitapide has been approved bythe FDA for patients with homozygous familial hypercholesterolaemia.8

Fibrates reduce the plasma triglyceride level by 30–50% andincrease the HDL-cholesterol level by 2–20%, but have littleeffect on the LDL-cholesterol level. Fibrates activateperoxisome proliferator-activated receptor α, which stimulatesthe oxidation of free fatty acids in the liver, diverting themfrom triglyceride synthesis; induces expression of lipoproteinlipase, the enzyme responsible for hydrolysing plasmatriglyceride; and inhibits synthesis of apoC-III, a protein thatdelays the catabolism of triglyceride-rich lipoproteins. Theelevation in the HDL-cholesterol level might be caused byincreased expression of the APOA1, APOA2, and ABCA1 genes. The results of trials involving �brates have been variable, although �brates have consistently produced a substantial reduction in the rate of cardiovascular events in individuals with hypertriglyceridaemia and a low HDL-cholesterol level.9

CETP inhibitors increase theHDL-cholesterol level by up to140%, decrease theLDL-cholesterol level by up to35%, and lower thelipoprotein(a) level by >30%.CETP transfers cholesterylesters from the HDL fraction,where it does not causeatherosclerosis, to the VLDLand LDL fractions, where it can cause atherosclerosis; inhibiting CETP is, therefore, potentially antiatherogenic. However, in a large, randomizedtrial, dalcetrapib had no effecton cardiovascular outcomes and, in another study, torcetrapib was associated with a signi�cant 25% increase in major cardiovascular events, and a58% increase in mortality. Large clinical trials are being conducted with anacetrapib and evacetrapib, which do notshare the adverse effects oftorcetrapib.10

Bile-acid-sequestering resins reduce the LDL-cholesterol level by about 20%. Resins bind bile acids in the intestine and disrupt their enterohepatic circulation. The liver is stimulated to divert cholesterol into bile-acid synthesis, a process that reduces the cellular content of cholesterol, which leads to a compensatory upregulation of LDL receptors. In 1984, use of the bile-acid-sequestering agent cholestyramine was shown to reduce the LDL-cholesterol level and the risk of cardiovascular events. However, these agents have largely been superseded by newer drugs.6

ApoB-100

ApoE

ApoC-IIIApoC-II

ApoA-VApoB-48

Chylomicron

LPL

Chylomicronremnant

ApoB-48

ApoE

ApoE

LIPC

LPL

LDL

CETP

CETPinhibitors

ApoA-I

Endosome

Nucleus

Statins

TriglycerideCholesterol

Fibrates

MTPinhibitors

LDLRAP1

Stomach

PCSK9LDLRAP1

Dietary fat

Liver

MTP

ApoB-48Duodenum

ApoB antisenseoligonucleotides ApoB-100

ApoB-100

ApoE

Pre-βHDL

HDLIDL

VLDL

Endosome

Bile-acid-sequestering resins

Cholesterol-absorptioninhibitors

VLDL

Cholesterol

Triglyceride

Endosome

LDLRAP1 mutationsAutosomal-recessive hypercholesterolaemia LDL-cholesterol level(603813, 605747)

LDLR mutationsFamilial hypercholesterolaemia LDL-cholesterol level(143890, 606945)

ApoB-100

ApoB-100

PCSK9 gain-of-function mutationsAutosomal-dominant hypercholesterolaemia LDL-cholesterol level (603776, 607786)PCSK9 loss-of-function mutationsPCSK9 de�ciency LDL-cholesterol level (607786)

PCSK9 inhibitors

Dietaryand biliary

sterol

IBAT

APOB ligand-bindingmutationsFamilial defective apoB LDL-cholesterol level(144010, 107730)APOB structural mutationsHypobetalipoproteinaemia Levels of ApoB-containing lipoproteins(107730)

ApoC-IIApoC-III

ApoC-IIApoC-IIILysosome

ApoB-containing lipoproteins

PCSK9

Supp

lem

ent

to N

atur

e P

ublis

hing

Gro

up jo

urna

ls

REGENERONDyslipidaemia and its treatmentRobert A. Hegele and Philip Barter

Disorders of plasma lipid and lipoprotein metabolism are well recognized as causative factors in the development of atherosclerotic cardiovascular disease. The rational management of such disorders requires an understanding of the factors that regulate plasma lipid metabolism and how abnormalities of such factors lead to dyslipidaemia. This poster displays the main lipid-metabolism pathways in the body, including synthesis in tissues and the interaction and transfer of lipids between the intestines, liver, blood, and peripheral tissues. The major classes of lipoproteins that transport lipids

in blood plasma, and the factors involved in their assembly, interconversion, and catabolism are shown. Points at which monogenetic mutations affect protein concentration, function, and that lead (often in combination with lifestyle factors) to dyslipidaemia are identified. With this knowledge, therapeutic targets can be identified, and we can understand how existing lipid-modifying drugs as well as novel agents under development target these pathways, with the potential to correct the dyslipidaemia and reduce the risk of a major cardiovascular event.1,2

Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York, USA, that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron markets medicines for eye diseases, colorectal cancer, and a rare inflammatory condition, and has product candidates in development in other areas of high unmet medical need, including hypercholesterolaemia, oncology, rheumatoid arthritis, allergic asthma, and atopic dermatitis.

Sanofi, an integrated global health-care leader, discovers, develops, and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of health care with seven growth platforms: diabetes mellitus solutions, human vaccines, innovative drugs, consumer health care, emerging markets, animal health, and the new Genzyme.

Since 2007, the Regeneron and Sanofi collaboration has been at the forefront of developing innovative new therapies that seek to address current unmet medical needs. The collaboration brings forth the best of both companies—technology, scientific expertise, commercial experience, and a focus on patient needs.

Abbreviations ABCA1 ATP-binding cassette sub-family A member 1ABCG1 ATP-binding cassette sub-family G member 1Apo apolipoproteinCETP cholesteryl ester transfer proteinFATPs fatty acid transport proteinsHDL high-density lipoprotein HMG-CoA 3-hydroxy-3-methylglutaryl-coenzyme AIBAT ileal sodium/bile acid cotransporterIDL intermediate-density lipoproteinLCAT phosphatidylcholine-sterol acyltransferaseLDL low-density lipoproteinLDLRAP1 low-density lipoprotein receptor adapter protein 1LIPC hepatic triacylglyercerol lipaseLPL lipoprotein lipaseLRP1 low-density lipoprotein receptor-related protein 1MTP microsomal triglyceride transfer protein

NPC1L1 Niemann–Pick C1-like protein 1PCSK9 proprotein convertase subtilisin/kexin type 9SR-B1 scavenger receptor class B member 1VLDL very-low-density lipoprotein

Information on monogenic dyslipidaemias is formatted: Gene name | Clinical disorder Primary biochemical disturbance (OMIM® reference)

References1. Gotto, A. M. Jr & Moon, J. E. Pharmacotherapies for lipid modification: beyond the statins. Nat. Rev. Cardiol. 10, 560–570 (2013).2. Watts, G. F., Ooi, E. M. M. & Chan, D. C. Demystifying the management of hypertriglyceridaemia. Nat. Rev. Cardiol. 10, 648–661 (2013).3. Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376, 1670–1681 (2010).

4. Marais, A. D. & Blomm, D. J. Recent advances in the treatment of homozygous familial hypercholesterolaemia. Curr. Opin. Lipidol. 24, 288–294 (2013).5. Petrides, F. et al. The promises of PCSK9 inhibition. Curr. Opin. Lipidol. 24, 307–312 (2013).6. Couture, P. & Lamarche, B. Ezetimibe and bile acid sequestrants: impact on lipoprotein metabolism and beyond. Curr. Opin. Lipidol. 24, 227–232 (2013).7. Lavigne, P. M. & Karas, R. H. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J. Am. Coll. Cardiol. 61, 440–446 (2013).8. Cuchel, M. & Rader, D. J. Microsomal transfer protein inhibition in humans. Curr. Opin. Lipidol. 24, 246–250 (2013).9. Jun, M. et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 375, 1875–1884 (2010).10. Barter, P. J. & Rye, K. A. Cholesteryl ester transfer protein inhibition as a strategy to reduce cardiovascular risk. J. Lipid Res. 53, 1755–1766 (2012).

Affiliations and competing interestsBlackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 100 Perth Drive, London, ON N6A 5K8, Canada (R. A. Hegele). Centre for Vascular Research, Department of Medicine, University of New South Wales, High Street, Kensington, Sydney, NSW 2052, Australia (P. Barter).R. A. Hegele declares that he has received research support from Amgen and Merck; and received honoraria from, and is an advisory board member for, Aegerion, Amgen, Genzyme, Merck, and Valeant. P. Barter declares that he has received research support from Merck and Pfizer; honoraria from Amgen, AstraZeneca, Kowa, MSD, Novartis, Pfizer, and Roche; and is an advisory board member for AstraZeneca, CSL, Kowa, Lilly, Merck, Pfizer, and Roche.

Edited by Gregory B. S. Lim; designed by Laura Marshall.The poster content is peer-reviewed and editorially independent.

© 2013 Nature Publishing Group.http://www.nature.com/nrcardio/posters/dyslipidaemia/