Beneficial effect of early initiation of lipid-lowering therapy following renal transplantation.
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.
Holdaas
Hallvard
H
Rikshospitalet, Sognsvannsvn 20, Oslo 0072, Norway. hallvard.holdaas@rikshospitalet.no
Fellström
Bengt
B
Jardine
Alan G
AG
Nyberg
Gudrun
G
Grönhagen-Riska
Carola
C
Madsen
Sören
S
Neumayer
Hans-Hellmut
HH
Cole
Edward
E
Maes
Bart
B
Ambühl
Patrice
P
Logan
John O
JO
Staffler
Beatrix
B
Gimpelewicz
Claudio
C
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
D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin