Comparison of sirolimus and everolimus in their effects on blood lipid profiles and haematological parameters in heart transplant recipients

Abstract

The mTOR (mammalian target of rapamycin) inhibitors sirolimus (SRL) and everolimus (EVL) are potent immunosuppressive agents, which allow reducing the dose of the nephrotoxic calcineurin inhibitors cyclosporin and tacrolimus (TAC) in solid organ transplant recipients. However, there is evidence that mTOR inhibitors may lead to myelosuppression and dyslipidemia/hyperlipidemia. We therefore performed a retrospective analysis in heart transplant recipients with renal insufficiency, who received 3.0 mg/d SRL (SRL group; n = 28) or 1.5 mg/d EVL (EVL group; n = 27) each in combination with a reduced TAC dose for at least one yr. Fewer cardiac rejections, but a similar rate of infections occurred in the EVL group compared with the SRL group indicating that the administered EVL dose resulted in a potent immunosuppression. Serum triglyceride and total cholesterol concentrations rose significantly in the SRL group but not in the EVL group. In the SRL group only, the frequency of statin use increased significantly during follow-up. The EVL group showed a significant rise in HDL cholesterol levels during follow-up. There was a slight transient fall in haemoglobin concentrations in the SRL group but not in the EVL group. Leucocyte counts fell significantly in both study groups. However, no cases of leucopenia and also no cases of thrombopenia occurred. In summary, we could demonstrate that in heart transplant recipients with renal insufficiency the introduction of 1.5 mg/d EVL in combination with a reduced TAC dose is effective in preventing cardiac rejections and has less adverse effects on lipid metabolism than the usually prescribed SRL dose, whereas both therapy regimens are not associated with major haematological side-effects.