Expanded-dose simvastatin is effective in homozygous familial hypercholesterolaemia

Atherosclerosis
Frederick J RaalM R Melino

Abstract

Patients with homozygous familial hypercholesterolaemia (HFH) have abnormalities in both low-density lipoprotein (LDL) receptor alleles, resulting in severe hypercholesterolaemia and premature coronary heart disease. Limited treatment options are available and the response to drug therapy has been poor. In the present paper, we have evaluated the efficacy and safety of simvastatin at doses beyond the current maximal dose of 40 mg/day in patients with HFH. After a 4 week placebo diet run-in period, 12 patients with well-characterized HFH were randomized to simvastatin 80 mg/day administered in three divided doses (n = 8; group 1) or 40 mg once daily (n = 4; group 2). After 9 weeks, the dose in group 1 was increased to 160 mg/day while the dose in group 2 was kept at 40 mg/day, but with the drug given in three divided doses and treatment continued for an additional 9 weeks. All 12 patients completed the study and there were no serious or unexpected adverse effects. LDL-cholesterol concentrations fell by 14% at the 40 mg/day dose, but were reduced further at the higher doses (25% at the 80 mg/day and by 31% at the 160 mg/day dosage, P < 0.0001). Excretion of urinary mevalonic acid, as an index of in vivo cholesterol biosynthesis, ...Continue Reading

References

Aug 1, 1979·The Journal of Clinical Investigation·D W BilheimerS M Grundy
Jan 1, 1992·Human Mutation·H H HobbsJ L Goldstein
Jan 1, 1992·European Journal of Clinical Pharmacology·L SlungaG H Dahlén
Feb 1, 1990·Nature·J L Goldstein, M S Brown
Sep 1, 1989·The Journal of Clinical Investigation·E LeitersdorfH H Hobbs
Jul 7, 1988·The New England Journal of Medicine·S M Grundy
Apr 4, 1986·Science·M S Brown, J L Goldstein
Jul 1, 1987·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·J C GibsonH C Seftel
Jun 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·J F Graadt van RoggenM J Kotze
Mar 1, 1995·The Journal of Clinical Investigation·D J RaderM Grossman
Jan 1, 1997·The American Journal of Cardiology·M H DavidsonJ A Tobert
Feb 1, 1994·Current Opinion in Lipidology·B R Gordon, S D Saal

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Citations

Dec 21, 2000·Current Atherosclerosis Reports·D M Black
Jan 5, 2002·Current Atherosclerosis Reports·A D MaraisJ C Firth
May 31, 2013·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Caroline M Perry
Dec 23, 1998·Atherosclerosis·C A Aguilar-SalinasG Schonfeld
Aug 3, 2002·European Journal of Clinical Investigation·C A Dane-StewartT G Redgrave
May 2, 2002·Therapeutic Apheresis : Official Journal of the International Society for Apheresis and the Japanese Society for Apheresis·Jean-Bernard PalcouxGeorges Malpuech
Jul 24, 2012·Metabolic Syndrome and Related Disorders·Vanessa PanzFrederick Raal
Jun 18, 2002·Journal of Cellular and Molecular Medicine·C Stancu, A Sima
May 9, 2012·Heart Views : the Official Journal of the Gulf Heart Association·Rachel Hajar
Dec 3, 2013·Current Atherosclerosis Reports·Salman J BandealiSalim S Virani
Nov 22, 2011·Future Medicinal Chemistry·Taichi Ohshiro, Hiroshi Tomoda
Nov 1, 2009·Expert Opinion on Medical Diagnostics·Adie Viljoen, Anthony S Wierzbicki
Mar 30, 2005·Expert Opinion on Drug Safety·Rodrigo AlonsoPedro Mata
Aug 12, 2003·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Pedro MataJuan Badimón
Dec 2, 2004·Expert Opinion on Pharmacotherapy·Terje R Pedersen, Jonathan A Tobert
Dec 4, 2014·Expert Opinion on Therapeutic Patents·Taichi Ohshiro, Hiroshi Tomoda
Mar 15, 2015·Cardiology and Therapy·Osman Najam, Kausik K Ray
Mar 9, 2012·Atherosclerosis·Frederick J Raal, Raul D Santos
Jan 21, 2000·Preventive Medicine·R R WilliamsS C Hunt
Nov 21, 2014·Current Atherosclerosis Reports·Claudia Stefanutti, Gilbert R Thompson
May 30, 2003·The Annals of Pharmacotherapy·Vincent F Mauro, Chad E Tuckerman
Oct 30, 2015·Circulation·Samuel S GiddingUNKNOWN American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascula
Jan 19, 2000·Circulation·D J MaronM F Linton
Mar 8, 2018·Critical Care : the Official Journal of the Critical Care Forum·Joseph G H LeeKeith R Walley
Jun 20, 2003·Nature Reviews. Drug Discovery·Jonathan A Tobert
Sep 4, 2020·Expert Opinion on Therapeutic Patents·Vishal P ZambreSanjay D Sawant
May 24, 2017·Clinical Reviews in Allergy & Immunology·Amir Abbas MomtaziAmirhossein Sahebkar
Jun 16, 2017·Expert Opinion on Biological Therapy·Giacomo PucciGiuseppe Schillaci

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