SAN DIEGO, Nov. 16 /PRNewswire/ -- Results from separate analyses from the Assessment of Lescol in Renal Transplantation (ALERT) study demonstrate that lipid levels are key risk factors for myocardial infarction (MI) and cardiac death in renal transplant recipients. In addition, early introduction of fluvastatin shortly following transplantation significantly reduced the risk of coronary heart disease (CHD).
These findings were presented at the 36th Annual Meeting of the American Society of Nephrology (ASN) in San Diego by Hallvard Holdaas, MD, Department of Medicine, Rikshospitalet University Hospital (National Hospital), Oslo, Norway and principal ALERT investigator.
“Cardiovascular disease is the leading cause of death, responsible for up to 70%, in renal transplant patients. Findings from ALERT are important as the relationship between lipid profile and cardiac events had not been clearly established in this high-risk patient population,” said Dr. Holdaas.
ALERT Subgroup Analyses
In renal transplant patients subtle changes in lipid levels are key risk factors for cardiovascular disease and cardiac death. In the ALERT study 2,102 patients with cholesterol levels between 4.0 to 9.0 mmol/l were randomized to receive double blind treatment with fluvastatin or placebo. An increase of 1 mmol/l in total cholesterol and low-density lipoprotein (LDL) cholesterol was associated with an increase in risk for CHD of 31 percent (p=0.0011) and 41 percent (p=0.0002), respectively; while an increase of 1 mmoml/l of high-density lipoprotein (HDL) cholesterol decrease in risk of CHD of 45 percent (p=0.0169); and lastly, a one unit increase in triglycerides resulted in only a 11 percent increase in CHD (p=0.0041).
A second ALERT subgroup analysis assessed the effect of time from last transplantation to introduction of fluvastatin treatment. In patients starting fluvastatin less than 4.5 years after transplantation, the risk of coronary heart disease was significantly reduced by 56% (p=0.002) compared with those on placebo.
When patients were categorized into groups divided by two-year intervals since their last transplant, fluvastatin reduced the relative risk for coronary heart disease by 54%, 64%, 45% and 14% when treatment was initiated at 0-2, 2-4, 4-6 and more than six years respectively. The risk reduction for patients initiating therapy at 0-2 years versus those initiating more than six years after transplantation was 59% (p=0.0328). The findings also demonstrated that fluvastatin is safe in this complicated patient population and early intervention provides the greatest benefit.
“Results of the subgroup analysis confirm that treatment with fluvastatin introduced shortly after renal transplantation significantly reduces the risk of coronary heart disease and did not increase the likelihood of experiencing side effects. Fluvastatin has proven to be uniquely safe in renal transplant patients on multiple medication including immunosuppressive therapy with cyclosporin,” said Dr. Holdaas.
ALERT Trial Design
The ALERT trial is the largest prospective study in renal transplant recipients and the first to study cardiac and renal outcomes in this patient population. Investigators compared the long-term effect of fluvastatin (40-80 mg daily) versus placebo on major adverse cardiac event (MACE)-free survival in renal-transplant patients with mild to moderate hypercholesterolemia receiving immunosuppressive therapy containing cyclosporin. ALERT enrolled 2,102 patients in nine countries. Patients were followed for a minimum of five and a maximum of six years. Novartis Pharma AG, manufacturers of Lescol(R) (fluvastatin), supported the ALERT trial with a research grant and provision of study medications.
Treatment with Lescol demonstrated a favorable trend towards reduction in the risk of MACE, the primary endpoint for this trial, although the difference compared to placebo was not statistically significant (p=0.139). On the hard cardiovascular endpoints, treatment with Lescol (40-80 mg daily) demonstrated a significant 38% reduction in the risk of cardiac death (p=0.031), a 32% reduction in the risk of non-fatal MI (p=0.050) and a 35% reduction in the cumulative incidence of cardiac death or first non-fatal MI (p=0.005).
Rikshospitalet University Hospital (National Hospital), founded in 1826, has special assignments in research and the development of new methods of treatment. In Norway, Rikshospitalet plays an important part as a highly specialized hospital with expert knowledge of the treatment of rare and complicated disorders. Rikshospitalet covers the whole country in various fields, including organ and bone marrow transplants, advanced neurosurgery, and treatment of children with congenital malformations.
Contact: Karen Dombek (MCS Public Relations) Office: 1-800-477-9626 Cell: 1-908-244-6411
Rikshospitalet University Hospital
CONTACT: Karen Dombek of MCS Public Relations, Office, 1-800-477-9626,or Cell, +1-908-244-6411, for Rikshospitalet University Hospital
Web site: http://www.mcspr.com/
