Journal Article

Two-Year Statin Therapy Does Not Alter the Progression of Intima-Media Thickness in Patients With Type 2 Diabetes Without Manifest Cardiovascular Disease

Hein Putter, Edith D. Beishuizen, Jouke T. Tamsma, Marcel A. van de Ree, A. Edo Meinders, J. Wouter Jukema, J. Carel M. van der Vijver, Menno V. Huisman

2004

Overview

Two-Year Statin Therapy Does Not Alter the Progression of Intima-Media Thickness in Patients With Type 2 Diabetes Without Manifest Cardiovascular Disease Edith D. Beishuizen , MD 1 , Marcel A. van de Ree , MD, PHD 2 , J. Wouter Jukema , MD, PHD 3 , Jouke T. Tamsma , MD, PHD 1 , J. Carel M. van der Vijver , MD, PHD 4 , A. Edo Meinders , MD, PHD 1 , Hein Putter , PHD 5 and Menno V. Huisman , MD, PHD 1 1 Department of General Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands 2 Department of Internal Medicine, Diakonessenhuis, Utrecht, the Netherlands 3 Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands 4 Department of Internal Medicine, Leyenburg Hospital, the Hague, the Netherlands 5 Department of Biostatistics, Leiden University Medical Center, Leiden, the Netherlands Address correspondence and reprint requests to E.D. Beishuizen, Department of General Internal Medicine, C1-R41, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands. E-mail: e.d.beishuizen{at}lumc.nl or m.v.huisman{at}lumc.nl Abstract OBJECTIVE —Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness (IMT) in type 2 diabetic patients without manifest CVD. RESEARCH DESIGN AND METHODS —A randomized, placebo-controlled, double-blind clinical trial was performed in 250 patients with type 2 diabetes. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change of mean common carotid IMT, as measured by B-mode ultrasound, over 2 years. RESULTS —Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years. There was no significant difference in IMT change in any carotid segment between the groups. LDL cholesterol was reduced by 25% in the statin group and increased by 8% in the placebo group ( P < 0.001). Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group ( P = 0.006). CONCLUSIONS —There was no effect of 2 years’ statin therapy on carotid IMT in type 2 diabetic subjects. The natural history of IMT in our patients was milder than anticipated. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. Prognostic tools other than IMT should be explored in this patient group. ALT, alanine aminotransferase CAD, coronary artery disease CVD, cardiovascular disease IMT, intima-media thickness Footnotes A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Accepted September 11, 2004. Received June 25, 2004. DIABETES CARE

• Publisher: American Diabetes Association
• Subject: Associated diseases and complications / Biological and medical sciences / Body Mass Index / Cardiovascular disease / Cardiovascular diseases / Carotid Arteries - drug effects / Carotid Arteries - pathology / Cholesterol - blood / Diabetes / Diabetes Mellitus, Type 2 - drug therapy / Diabetes Mellitus, Type 2 - physiopathology / Diabetes. Impaired glucose tolerance / Diabetic Angiopathies - epidemiology / Diabetic Angiopathies - physiopathology / Disease Progression / Dosage and administration / Double-Blind Method / Drug therapy / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Female / General and cellular metabolism. Vitamins / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use / Lipids - blood / Male / Medical sciences / Middle Aged / Pharmacology. Drug treatments / Placebo effect / Placebos / Pyridines - therapeutic use / Side effects / Statins / Time Factors / Triglycerides - blood / Tunica Intima - drug effects / Tunica Intima - pathology / Tunica Media - drug effects / Tunica Media - pathology / Type 2 diabetes