A Novel Immunosuppressive Regiment for Cardiac Transplant Patients

Abstract

Heart transplantation remains curative for end-stage heart failure. The choice between immunosuppressive regimens is guided by several principles: mitigating the risk of rejection early after transplantation, limiting drug toxicity of immunosuppressants, and minimizing over-suppression. We sought to investigate the efficacy of a novel immunosuppressive regimen targeting a lower therapeutic range (LTR) for Tacrolimus without antecedent induction therapy compared with a standard therapeutic range (STR). The protocol was implemented after 2016 and included the administration of Tacrolimus to a goal trough of 6-8 ng/mL immediately post transplant, Mycophenolate mofetil 1000-15000 mg BID, and Prednisone 1 mg/kg/day post-op divided into two doses and tapered by 5 mg Daily. A retrospective chart review was performed comparing transplant outcomes utilizing the novel LTR immunosuppression regimen compared to STR from 2008-2019. Primary outcomes included infection, bone marrow suppression and rejection within the first 3 years of transplantation. Of the 83 patients analyzed, 25 (30%) received the lower Tacrolimus dosing regimen (LDR), and 58 received the standard dosing regimen (SDR). Patients in the LDR group were younger (56.2 +/- 12.2 years vs 61.8 +/- 10.4 years) and less likely to be male (68% vs 87.9%). Rates of high risk CMV donor/recipient status was similar between the two groups. There was no statistically significant difference between the LDR group and SDR group with respect to rates of infection (44% vs 34.5%, p=0.41), bone marrow suppression (20% vs 13.8%, p=0.47), or > 2R CMR (24% vs 32.8%, p=0.42). In this single-center study we compared a conventional post-transplant immunosuppression regimen with one that utilized a lower Tacrolimus trough goal (6-8ng/mL). There was no statistical difference between the two groups in rates of rejection, bone marrow suppression, or infectious complications. We present a successful novel immunosuppression regiment that could serve to benefit patients with intolerance to higher doses of calcineurin inhibitors with no adverse outcomes. Future studies are needed to determine the impact of LTR on renal function.