A double-blind placebo controlled trial of simvastatin for the treatment of dyslipidaemia in renal allograft recipients

Background: With current techniques, renal failure patients are now able to regain near-normal health following renal transplantation. However, the de velopment of premature cardiovascular disease is a major problem. Dyslipida emia may be an important contributor to this. The use of lipid lowering age nts in renal allograft recipients has been limited by potential interaction of these agents with the now widely used immunosuppressive agent, cyclospo rine. Aim: This study was designed to investigate efficacy and safety of simvasta tin in subjects taking either cyclosporine or azothioprine post renal trans plantation. Methods: Fifty-one subjects (32 females, 19 males - mean age 51 +/- 12.5 yr ) who were at least 1 yr post transplant, had creatinine less than or equal to 2.5 mmol/L and a total cholesterol greater than or equal to 6 mmol/L we re enrolled in a prospective, double-blind, placebo-controlled study. After an initial 10-wk dietary period, the last 4 wk on placebo, subjects were r andomised to receive either 5 mg simvastatin/d for 6 wk followed by 10 mg s imvastatin/d for 6 wk, or matching placebo. After this 12-wk double-blind p hase, there was an open-label phase when ail subjects were treated with 10 mg simvastatin/d for a period of 36 wk. Results: Compared to placebo, 5 mg simvastatin/d significantly decreased to tal cholesterol by 20% (p < 0.01), low-density lipoprotein cholesterol (LDL cholesterol) by 29% (p < 0.01), and Apolipoprotein B (ApoB) by 26% (p < 0. 01). Increasing simvastatin to 10 mg/d did not lead to further significant changes. But high-density lipoprotein cholesterol (HDL cholesterol) increas ed by 9% (p < 0.01) and Apolipoprotein Al (ApoAl) by 7% (p < 0.01) only on 10 mg simvastatin/d. During the open-label phase, subjects previously rando mised to placebo achieved similar significant changes to their lipoprotein profile. The benefits achieved from simvastatin were maintained to the end of the study. There were three withdrawals from the study, all from the sim vastatin/cyclosporine group. Two subjects had musculoskeletal pain and 1 ha d abdominal pain Minor adverse events were similar in both the simvastatin- and placebo-treated groups. Conclusion: Low-dose simvastatin is an effective and well-tolerated agent i n the treatment of dyslipidaemia in renal allograft recipients.