Lancet. 2003 Jun 14;361(9374):2024-31. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre， randomised， placebo-controlled trial. (ALERT) Holdaas H， Fellstrom B， Jardine AG， Holme I， Nyberg G， Fauchald P， Gronhagen-Riska C， Madsen S， Neumayer HH， Cole E， Maes B， Ambuhl P， Olsson AG， Hartmann A， Solbu DO， Pedersen TR; Assessment of LEscol in Renal Transplantation (ALERT) Study Investigators. hallvard.holdaas@rikshospitalet.no
BACKGROUND: Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population， their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population.
METHODS: We did a multicentre， randomised， double-blind， placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event， defined as cardiac death， non-fatal myocardial infarction (MI)， or coronary intervention procedure. Secondary endpoints were individual cardiac events， combined cardiac death or non-fatal MI， cerebrovascular events， non-cardiovascular death， all-cause mortality， and graft loss or doubling of serum creatinine. Analysis was by intention to treat.
FINDINGS: After a mean follow-up of 5.1 years， fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06]， p=0.139) was not significant， although there were fewer cardiac deaths or non-fatal MI (70 vs 104， 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups.
INTERPRETATION: Although cardiac deaths and non-fatal MI seemed to be reduced， fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.