Atherosclerosis 197 (2008) 400–406 A dose-titration and comparative study of rosuvastatin and atorvastatin in patients with homozygous familial hypercholesterolaemia A. David Marais a,∗ , Frederick J. Raal b , Evan A. Stein c , Daniel J. Rader d , James Blasetto e , Michael Palmer f , Wim Wilpshaar f a Groote Schuur Hospital & University of Cape Town, Lipidology, Internal Medicine, 5th Floor C Barnard Building, UCT Health Science Faculty, Anzio Road, Cape Town 7925, South Africa b Johannesburg Hospital & University of Witwatersrand, Johannesburg, South Africa c Medical Research Laboratories, Highland Heights, Kentucky, USA d Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA e AstraZeneca LP, Wilmington, Delaware, USA f AstraZeneca, Alderley Park, Cheshire, UK Received 28 August 2006; received in revised form 26 April 2007; accepted 21 June 2007 Available online 28 August 2007 Abstract This study assessed the efficacy of rosuvastatin for reducing plasma low-density lipoprotein (LDL) cholesterol after 18 weeks of open-label, forced titration in patients with homozygous familial hypercholesterolaemia (hoFH) and compared the efficacy of rosuvastatin 80 mg and atorvastatin 80 mg. Forty-four patients aged 8–63 years (body mass ≥32 kg) entered the study; 4 had portacaval shunts and 11 were receiving plasmapheresis. Patients sequentially received rosuvastatin 20, 40 and 80 mg/day for 6 weeks. Patients remaining in the trial after 18 weeks received double-blind, randomised crossover treatment with rosuvastatin 80 mg/day and atorvastatin 80 mg/day for 6 weeks each. After 18 weeks, mean (S.D.)% reduction from baseline in LDL cholesterol was 22 (21)% overall and by 26 (15)% in 29 patients who neither had a portacaval shunt nor were receiving plasmapheresis. Seventy-two percent of the patients had ≥15% reductions in LDL cholesterol and were considered responders and included patients who had portacaval shunts or were receiving plasmapheresis. Mean LDL reductions from baseline after crossover treatment (n = 21) with rosuvastatin 80 mg and atorvastatin 80 mg were 19 and 18%, respectively. All treatments were well tolerated. Rosuvastatin may have therapeutic value in the management of hoFH. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Homozygous familial hypercholesterolaemia; Rosuvastatin; HMGCoA reductase inhibitors 1. Introduction In homozygous familial hypercholesterolaemia (hoFH), both genes for the low-density lipoprotein (LDL) receptor contain mutations that result in the absence (receptor- negative) or defective function of the receptor [1]. Clinical presentation, usually in childhood, is characterised by cuta- neous and tendinous xanthomata and extremely elevated plasma LDL cholesterol concentrations. This condition is associated with early, widespread and severe atherosclero- ∗ Tel.: +27 21 406 6166; fax: +27 21 406 6396. E-mail address: dmarais@capeheart.uct.ac.za (A.D. Marais). sis. While dietary and pharmacologic therapy (e.g., with statins and cholesterol absorption inhibitors) may improve this condition, additional therapeutic strategies such as plasmapheresis, portacaval shunting, ileal bypass and liver transplantation are commonly used to control the dyslipi- daemia [2–7]. Statins inhibit HMG-CoA reductase and prevent the conversion of HMG-CoA to mevalonate, a precursor of cholesterol. Reduced cholesterol synthesis in the hepatocyte results in the upregulation of LDL receptors and increased clearance of LDL cholesterol from the circulation. Initial experience with statins alone or as an adjunct to plasma- pheresis showed little benefit in hoFH [8,9]. Greater LDL 0021-9150/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2007.06.028