Kidney-transplant patients are at an increased risk of premature cardiovascular disease; many transplant recipients have pre-existing cardiovascular disease at the time of transplantation and immunosuppressive therapy may aggravate existing risk factors or promote the development of new ones, notably high cholesterol concentration and high blood pressure. Statins have known benefits in reducing cardiovascular disease (including risk reduction among people with normal cholesterol concentrations), although their effect among kidney-transplant patients has not been proven.
In an international multicentre study, Hallvard Holdaas from Norway's National hospital, Oslo, and colleagues investigated the effects of the statin fluvastatin in around 2100 people (from Belgium, Denmark, Finland, Germany, Norway, Sweden, Switzerland, the UK, and Canada) who had previously undergone kidney transplantation. All participants had baseline cholesterol concentrations between 4 and 9 millimols per litre; half were randomised to receive fluvastatin, the other half to placebo. Follow-up was done five to six years later. 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 included individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, and all-cause mortality.
People in the fluvastatin group had their cholesterol concentrations reduced by around a third compared with individuals given placebo. There were fewer cardiac deaths or non-fatal MI (70 compared with 104) in the fluvastatin group compared with placebo, although the overall difference in primary endpoints (including coronary intervention procedures) was not statistically significant compared with placebo.
Hallvard Holdaas comments: "As many as 50% of renal transplant recipients are now treated with statins, which reflects the widespread acceptance of data from other populations, particularly for the secondary prevention of cardiac disease and in diabetes. These other statin studies have shown that statins are effective in patients with mild renal failure who are at increased cardiovascular risk, some of whom may ultimately require renal transplantation. This study shows a similar beneficial effect for fluvastatin, a statin that has minimal interaction with immunosuppressive therapy, in patients at the opposite end of the spectrum of renal failure."
Contact: Dr Hallvard Holdaas, Medical Department, National Hospital, 0027 Oslo, Norway;
T) +47 230 71700;
F) +47 230 71246;
E) hallvard.holdaas@rikshospitalet.no
Journal
The Lancet