The combination of sirolimus and tacrolimus for primary immunosuppression after heart transplantation –3-year-results

Objectives: Sirolimus and tacrolimus are immunosuppressants competing for the same binding-protein. This study evaluated the efficacy and safety of the immunosuppressive combination tacrolimus and sirolimus after heart transplantation using subtherapeutic trough levels for each compound.

Methods: 33 patients were included into a prospective pilot-study. Target trough levels for sirolimus and tacrolimus were 6–8ng/ml for the first year and 5–6ng/ml for the further course. Steroids were completely withdrawn 6 months after HTx. Mean follow-up was 1100±226 days.

Results: Survival was 100%. The immunosuppressive regimen was switched in 6 patients (2 renal insufficiency, 2 polineuropathy, diarrhea, neoplasm). One acute rejection episode was detected and successfully treated 54 days after HTx. Mean trough levels for tacrolimus und sirolimus were 8.28±1.74 and 6.27±1.02ng/ml, respectively. The incidence of infections was comparable to other combinations (1.5±1.39/pat) while a low incidence of viral infections was observed (0.19±0.4/pat). Side-effects occurred frequently (edema, aphtae, acne). 3 patients underwent pericardial drainage, 1 patient pleural drainage due to refractory effusions. After steroid-withdrawal the initially increased total cholesterol levels declined while creatinine levels increased steadily over time. 3 patients (9%) developed neoplasms (malign melanoma, PTLD, bronchial carcinoma). No new onset of macrovasculopathic changes was detected in the 3-year-angiograms.

Conclusion: The combination of tacrolimus and sirolimus is effective in the prevention of acute rejection and early onset vasculopathy even in low trough level ranges. Side effects were common and in some cases severe. Creatinine levels increased steadily despite low CNI-levels. Further randomized studies are needed to add further evidence to these data.