Effi cacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: A single-arm, open-label, phase 3 study

The Lancet

Volumn 381, Issue 9860, 2013, Pages 40-46

  Cuchel, Marina ^a   Meagher, Emma A ^a   Theron, Hendrik Du Toit ^b   Blom, Dirk J ^c,d,e   Marais, A David ^c,d,e   Hegele, Robert A ^f   Averna, Maurizio R ^g   Sirtori, Cesare R ^h   Shah, Prediman K ⁱ   Gaudet, Daniel ^j   Stefanutti, Claudia ^k   Vigna, Giovanni B ^l   Du Plessi, Anna M E ^m   Propert, Kathleen J ^a   Sasiela, William J ⁿ   Bloedon, Leanne T ^a,n   Rader, Daniel J ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b Netcare   (South Africa)

^c Department of Medicine ^*  (South Africa)

^d UNIVERSITY OF CAPE TOWN   (South Africa)

^e SOUTH AFRICAN MEDICAL RESEARCH COUNCIL   (South Africa)

^f ROBARTS RESEARCH INSTITUTE   (Canada)

^g UNIVERSITY OF PALERMO   (Italy)

^h OSPEDALE NIGUARDA CA GRANDA   (Italy)

ⁱ CEDARS SINAI MEDICAL CENTER   (United States)

^j UNIVERSITÉ DE MONTRÉAL   (Canada)

^k SAPIENZA UNIVERSITY OF ROME   (Italy)

^l UNIVERSITY OF FERRARA   (Italy)

^m UNIVERSITY OF PRETORIA   (South Africa)

ⁿ Aegerion Pharmaceuticals   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN A; APOLIPOPROTEIN B; ATORVASTATIN; CHOLESTEROL; EZETIMIBE; FIBRIC ACID DERIVATIVE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIPOPROTEIN; LOMITAPIDE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NICOTINIC ACID; ROSUVASTATIN; TRIACYLGLYCEROL; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL; BENZIMIDAZOLE DERIVATIVE; CARRIER PROTEIN; MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN;

ACUTE CORONARY SYNDROME; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANGINA PECTORIS; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BODY FAT; CHOLESTEROL BLOOD LEVEL; CLINICAL ARTICLE; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; FAMILIAL HYPERCHOLESTEROLEMIA; FEMALE; GASTROINTESTINAL DISEASE; HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; HUMAN; HYSTERECTOMY; LIPOPROTEIN BLOOD LEVEL; LIVER FAT; LOWER RESPIRATORY TRACT INFECTION; MALE; MENORRHAGIA; MULTICENTER STUDY; OPEN STUDY; PATIENT COMPLIANCE; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; SIDE EFFECT; THORAX PAIN; TREATMENT DURATION; TREATMENT WITHDRAWAL; TRIACYLGLYCEROL BLOOD LEVEL; BLOOD; DRUG ANTAGONISM; GENETICS; HOMOZYGOTE;

BENZIMIDAZOLES; CARRIER PROTEINS; CHOLESTEROL, LDL; FEMALE; HOMOZYGOTE; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; MALE;

MLCS; MLOWN;

EID: 84871945617     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(12)61731-0     Document Type: Article

References (24)

1. Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest 2003; 111: 1795-803.
2. Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th edn. New York: McGraw-Hill Information Services Company, 2001: 2863-913.
3. Macchiaiolo M, Gagliardi MG, Toscano A, Guccione P, Bartuli A. Homozygous familial hypercholesterolaemia. Lancet 2012; 379: 1330.
4. Kolansky DM, Cuchel M, Clark BJ, et al. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol 2008; 102: 1438-43.
5. Marais AD, Firth JC, Blom DJ. Homozygous familial hypercholesterolemia and its management. Semin Vasc Med 2004; 4: 43-50.
6. Raal FJ, Pilcher GJ, Panz VR, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation 2011; 124: 2202-07.
7. Gagné C, Gaudet D, Bruckert E, and the Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation 2002; 105: 2469-75.
8. Hudgins LC, Kleinman B, Scheuer A, White S, Gordon BR. Long-term safety and efficacy of low-density lipoprotein apheresis in childhood for homozygous familial hypercholesterolemia. Am J Cardiol 2008; 102: 1199-204.
9. Thompson GR, Barbir M, Davies D, et al. Efficacy criteria and cholesterol targets for LDL apheresis. Atherosclerosis 2010; 208: 317-21.
10. Thompson GR, Catapano A, Saheb S, et al. Severe hypercholesterolaemia: therapeutic goals and eligibility criteria for LDL apheresis in Europe. Curr Opin Lipidol 2010; 21: 492-98.
11. Starzl TE, Bilheimer DW, Bahnson HT, et al. Heart-liver transplantation in a patient with familial hypercholesterolaemia. Lancet 1984; 1: 1382-83.
12. Maiorana A, Nobili V, Calandra S, et al. Preemptive liver transplantation in a child with familial hypercholesterolemia. Pediatr Transplant 2011; 15: E25-29.
13. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 2010; 375: 998-1006.
14. Cuchel M, Bloedon LT, Szapary PO, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007; 356: 148-56.
15. Wetterau JR, Lin MC, Jamil H. Microsomal triglyceride transfer protein. Biochim Biophys Acta 1997; 1345: 136-50.
16. Wetterau JR, Gregg RE, Harrity TW, et al. An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits. Science 1998; 282: 751-54.
17. Raal FJ, Pilcher GJ, Illingworth DR, et al. Expanded-dose simvastatin is eff ective in homozygous familial hypercholesterolaemia. Atherosclerosis 1997; 135: 249-56.
18. Raal FJ, Pappu AS, Illingworth DR, et al. Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia. Atherosclerosis 2000; 150: 421-28.
19. Marais AD, Raal FJ, Stein EA, et al. A dose-titration and comparative study of rosuvastatin and atorvastatin in patients with homozygous familial hypercholesterolaemia. Atherosclerosis 2008; 197: 400-06.
20. Hudgins LC, Gordon BR, Parker TS, Saal SD, Levine DM, Rubin AL. LDL Apheresis: an eff ective and safe treatment for refractory hypercholesterolemia. Cardiovasc Drug Rev 2002; 20: 271-80.
21. Sachais BS, Katz J, Ross J, Rader DJ. Long-term effects of LDL apheresis in patients with severe hypercholesterolemia. J Clin Apher 2005; 20: 252-55.
22. Stefanutti C, D'Alessandri G, Russi G, et al. Treatment of symptomatic HyperLp(a)lipoproteinemia with LDL-apheresis: a multicentre study. Atheroscler Suppl 2009; 10: 89-94.
23. Hovland A, Marcovina S, Hardersen R, Enebakk T, Mollnes TE, Lappegard KT. Three different LDL apheresis columns efficiently and equally reduce lipoprotein (a) concentrations in patients with familial hypercholesterolemia and small apolipoprotein (a) particles. Transfus Apher Sci 2012; 46: 73-76.
24. Samaha FF, McKenney J, Bloedon LT, Sasiela WJ, Rader DJ. Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia. Nat Clin Pract Cardiovasc Med 2008; 5: 497-505.