Beneficial effect of omega-3 fatty acids on sirolimus- or everolimus-induced hypertriglyceridemia in heart transplant recipients

Background. Hyperlipidemia is an important complication after organ transplantation and may contribute to the development of posttransplant-accelerated coronary artery disease. Immunosuppressive therapy, especially mammalian target of rapamycin inhibitors, induces a considerable increase in cholesterol and triglyceride plasma levels. Omega-3 fatty acids (FAs) exert cardioprotective effects supporting a therapeutic role in cardiovascular conditions. Methods. An observational study of omega-3 FAs 4 g/day was performed in 15 heart transplant recipients with hypertriglyceridemia. Six patients received rapamycin, and nine received everolimus. Apart from one patient the immunosuppressive therapy was combined with mycophenolate mofetil, only one patient received steroids; two patients presented with diabetes. Results. Mean triglyceride levels before heart transplantation (HTx) were 137 +/- 54 mg/dL. After HTx, before sirolimus or everolimus treatment triglyceride level had increased to 188 +/- 67 mg/dL (P<0.05). Treatment with sirolimus or everolimus induced an increase in triglycerides to 354 +/- 107 mg/dL (P<0.001). Subsequent treatment with omega-3 FAs for 4 months resulted in a marked decrease in triglycerides to 226 +/- 74 mg/dL (P<0.001). All patients (100%) showed a reduction in triglyceride by more than 20% (responders). In 10 of 15 patients available 12-month data confirmed the long-term efficacy of omega-3 FAs treatment. There were no adverse events or any discontinuations; no changes in immunosuppression were required. Conclusions. Treatment with mammalian target of rapamycin inhibitors after HTx induces marked increase in serum levels of triglycerides. Omega-3 FAs significantly lower triglyceride levels and seem to be effective, safe, and well-tolerated in sirolimus- or everolimus-treated heart transplant recipients.