To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Routine Use of Cholesterol-Lowering Drug Improves Outcomes for Heart Transplant Recipients URL: http://www.pslgroup.com/dg/5D42.htm Doctor's Guide September 6, 1995
LOS ANGELES, Sept. 6, 1995 -- Treating heart transplant patients with a common cholesterol-lowering medication can significantly reduce post-transplant atherosclerosis, the major obstacle to increasing the long-term survival of transplant recipients, according to a study from the UCLA School of Medicine. Patients who received the drug pravastatin (Pravachol) had fewer signs of organ rejection, sharply cut their cholesterol levels and had significantly higher one-year survival rates, according to a report in the Sept. 7 edition of the New England Journal of Medicine. "These findings are very exciting and hold the promise of showing us how to increase the long-term survival of heart transplant recipients," said Dr. Jon Kobashigawa, lead author of the report and medical director of the UCLA Heart Transplant Program. Heart transplant recipients typically have high cholesterol levels, a result of the antirejection medicines they take and the familial histories that cause them to develop severe heart disease. Half of all heart transplant patients have significant coronary blockages within five years of surgery and the problem is one of the leading causes of death among heart transplant recipients. Researchers have long been interested in cholesterol-lowering drugs as a possible treatment for the atherosclerosis that occurs in most heart transplant recipients. Tests with other cholesterol-lowering drugs have been concerning because the agents can trigger the loss of muscle tissue by interacting with cyclosporine, an important immunosuppressant given to all transplant recipients. Pravastatin was found to be safe to give to transplant recipients, probably because it is less likely to enter muscle tissue, Kobashigawa said. The dramatic improvements triggered by pravastatin appear to be caused not just by the drug's cholesterol-lowering properties, but by a newly discovered mechanism that suppresses immune activity when taken along with cyclosporine, given to transplant recipients to fight organ rejection. However, there is no evidence that pravastatin decreases immune system activity in nontransplant patients, Kobashigawa said. The drug's success in combating post-transplant atherosclerosis holds implications for kidney, liver and lung transplants because similar mechanisms are a problem in those transplants. UCLA researchers followed 97 heart transplant patients for one year following their surgery, with half receiving pravastatin in addition to all usual post-transplant medications. They studied the patients for four factors: survival one year after transplant, clinical indicators of organ rejection, cholesterol levels and the progression of transplant coronary artery disease, the atherosclerosis that occurs in most heart transplant recipients. The key findings were: -- The number of clinically important rejection episodes were 70 percent lower in the group taking pravastatin. -- Cholesterol levels dropped by about 20 percent, from an average of 248 in the control group to an average of 193 in those taking the drug. -- Survival one year after primary transplant jumped to 95 percent for those who received the pravastatin versus 81 percent for those not taking the drug. -- Evidence of atherosclerosis in the patients taking the drug dropped by 50 percent as measured in a subgroup with a new imaging technology called intravascular ultrasound, which is more sensitive than standard angiography. Researchers also examined the activity of natural killer cells, a part of the immune system, in a subset of patients and found that patients taking pravastatin had fewer than half as many functioning as other patients. The results confirm that pravastatin acts to lower the immune system of the transplant patients. Based on the findings reported in the study, all new heart transplant recipients at UCLA are now placed on maintenance doses of pravastatin immediately following surgery. Kobashigawa is studying the long-term effects of pravastatin and other UCLA researchers have begun work to assess the drug's usefulness for kidney and liver transplants. Partial support for the study was provided by an unrestricted grant from Bristol-Myers Squibb, manufacturers of Pravachol. Other authors of the report are Dr. Steven Kalznelson, Dr. Hillel Laks, Dr. Jay Johnson, Dr. Lawrence Yeatman, Dr. Xiu Ming Wang, Dr. David Chia, Dr. Paul Terasaki, Alejandro Sabad, Gregory Cogert, Kevin Trosian, Dr. Michele Hamilton, Dr. Jaime Moriguchi, Dr. Nobuyuki Kawata, Dr. Antoine Hage and Dr. Davis Drinkwater of the UCLA School of Medicine; and Dr. Lynne Stevenson of Brigham and Women's Hospital, Boston. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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