Effect of Atorvastatin on Postcardiac Transplant Increase in Low-Density Lipoprotein Cholesterol Reduces Development of Intimal Hyperplasia and Progression of Endothelial Dysfunction Vincent Y. See, Jr., MD, David DeNofrio, MD, Lee Goldberg, MD, Gene Chang, MD, Brett Sasseen, MD, Daniel M. Kolansky, MD, Faith Pickering, RN, Andrew Kao, MD, Evan Loh, MD, and Robert L. Wilensky, MD Following cardiac transplantation, accelerated coronary disease limits long-term survival. Because statins may reduce the progression of the disease in part by their anti-inflammatory effects, this study was designed to assess if atorvastatin prevented neointimal hyperplasia and endothelial dysfunction independently of baseline cholesterol levels. Patients were randomized to usual therapy (n  13) or to 10 to 20 mg of atorvastatin (n  12). Control subjects received niacin when their low- density lipoprotein (LDL) cholesterol levels were >130 mg/dl (n  4). Neointimal hyperplasia by intracoronary ultrasonography, endothelial dependent vascular reac- tivity, and coronary flow reserve were measured at baseline and 1 year. Control group total cholesterol (203  11 to 200  13 mg/dl) and LDL (116  10 to 119  11 mg/dl) remained stable, whereas there was a non- significant reduction at 12 months in the atorvastatin group (total cholesterol 216  28 to 178  21 mg/dl; LDL 126  17 to 100  18 mg/dl). At 2 to 3 months there was a significant increase in total cholesterol and LDL cholesterol that was reduced with atorvastatin. At 1 year, patients taking atorvastatin showed a decrease in new or progressing lesions (2.5  1.7 vs 4.2  1.8 lesions/patient, p  0.02), progression of maximal in- timal thickness (0.12  0.07 vs 0.52  0.17 mm, p  0.04), and percent area stenosis (5.9  2.2% vs 19.0  5.5%, p  0.04). Atorvastatin ameliorated progressive endothelial dysfunction, whereas coronary flow reserve was unchanged in both groups. Atorvastatin adminis- tered to patients with normal or mild hypercholesterol- emia in the initial year after transplant reduced the initial increase in LDL cholesterol, and, by doing so, prevented the development and progression of coronary artery lesions and endothelial dysfunction with only mild long-term decreases in cholesterol levels. 2003 by Excerpta Medica, Inc. (Am J Cardiol 2003;92:11–15) T he aim of the present study was to evaluate the effect of atorvastatin on coronary lesion develop- ment and endothelial function in the initial year after transplantation, regardless of baseline cholesterol level. METHODS Twenty-five patients who underwent cardiac trans- plantation at the Hospital of the University of Penn- sylvania between December 1997 and September 1999 were prospectively enrolled and randomized. Patients were excluded if they were taking a statin or had a history of statin sensitivity, liver dysfunction, myositis, or active infection. Before discharge, pa- tients randomized to atorvastatin were started on 10 mg/day regardless of their low-density lipoprotein (LDL) cholesterol levels. The dose was increased at follow-up to achieve a LDL cholesterol level of  100 mg/dl. Control subjects received niacin to treat LDL cholesterol levels 130 mg/dl. All patients provided signed informed consent and the study was approved by the institutional review board of the University of Pennsylvania. All patients received standard immunosuppression with cyclosporine, mycophenolate mofetil, and pred- nisone. Two patients who could not tolerate mycophe- nolate were switched to azathioprine, and tacrolimus was substituted in 1 patient who could not tolerate cyclosporine. An early prednisone taper was initiated, with the goal of having all patients steroid-free 9 months after transplant. Routine surveillance endo- myocardial biopsy scored by International Society of Heart and Lung Transplantation criteria determined rejection. Early ischemia was not evaluated in these biopsy samples. Two patients who developed rejec- tion associated with hemodynamic compromise were treated with pulse steroids, and 1 required additional From the Cardiovascular Division, Hospital of the University of Penn- sylvania, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and Division of Cardiology, Tufts-New England Medi- cal Center, Boston, Massachusetts. Dr. See was supported by an Student Scholars in Cardiovascular Disease and Stroke Award from the American Heart Association, Dallas, Texas. Manuscript received January 7, 2003; revised manuscript received and accepted March 27, 2003. Address for reprints: Robert L. Wilensky, MD, Cardiovascular Division, Hospital of the University of Pennsylvania, 3400 Spruce Street, 9 Gates, Philadelphia, Pennsylvania 19104-4024. E-mail: robert.wilensky@uphs.upenn.edu. 11 ©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matter The American Journal of Cardiology Vol. 92 July 1, 2003 doi:10.1016/S0002-9149(03)00456-9