title: Beneficial effect of early initiation of lipid-lowering therapy following renal transplantation.
abstract: BACKGROUND
  Renal transplant recipients have a significantly reduced life expectancy, largely due to premature cardiovascular disease. The aim of the current analysis was to investigate the importance of time of initiation of therapy after transplantation, on the benefits of statin therapy.
  
  
  METHODS
  2102 renal transplant recipients with total cholesterol levels of 4.0-9.0 mmol/l were randomly assigned to treatment with fluvastatin (n = 1050) or placebo (n = 1052) and followed for a mean time of 5.1 years. The end-points were major cardiac events. The average median time from transplantation to randomization was 4.5 years (range: 0.5-29 years).
  
  
  RESULTS
  In patients starting treatment with fluvastatin <4.5 years after renal transplantation, the incidence of cardiac events was 4.6% over 5.1 years vs 9.2% in those on placebo (P = 0.007). Fluvastatin significantly reduced the risk of cardiac death and non-fatal myocardial infarction by 56% [risk ratio (RR): 0.44; 95% confidence interval (95% CI): 0.26-0.74; P = 0.002]. In a more detailed analysis patients were grouped into 2-year intervals (since the last transplantation). The frequency of cardiac death and non-fatal myocardial infarction was reduced by 3.2%, 5.1%, 9.6% and 8.2% with fluvastatin treatment as compared to 6%, 10.4%, 13.4% and 9.6% with placebo when treatment was initiated at 0-2, 2-4, 4-6 and >6 years, respectively. The risk reduction for patients initiating therapy with fluvastatin at years 0-2 (compared with >6 years) following transplantation was 59% (RR: 0.41; 95% CI: 0.18-0.92; P = 0.0328). This is also reflected in total time on renal replacement therapy: in patients in the first quartile (<47 months) fluvastatin use was associated with a risk reduction of 64% compared with 19% for patients in the fourth quartile (>120 months) (P = 0.033).
  
  
  CONCLUSIONS
  Our data support an early introduction of fluvastatin therapy in a population of transplant recipients at high risk of premature coronary heart disease.
authors.affiliation: Rikshospitalet, Sognsvannsvn 20, Oslo 0072, Norway. hallvard.holdaas@rikshospitalet.no
authors.forename: Hallvard
authors.initials: H
authors.lastname: Holdaas
authors.forename: Bengt
authors.initials: B
authors.lastname: Fellström
authors.forename: Alan G
authors.initials: AG
authors.lastname: Jardine
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nyberg
authors.forename: Carola
authors.initials: C
authors.lastname: Grönhagen-Riska
authors.forename: Sören
authors.initials: S
authors.lastname: Madsen
authors.forename: Hans-Hellmut
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Edward
authors.initials: E
authors.lastname: Cole
authors.forename: Bart
authors.initials: B
authors.lastname: Maes
authors.forename: Patrice
authors.initials: P
authors.lastname: Ambühl
authors.forename: John O
authors.initials: JO
authors.lastname: Logan
authors.forename: Beatrix
authors.initials: B
authors.lastname: Staffler
authors.forename: Claudio
authors.initials: C
authors.lastname: Gimpelewicz
mesh_terms: D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood; D003643:Death; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D040242:Risk Reduction Behavior
chemical_list: D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin