*Purpose: Obesity is common after heart transplant (HT), resulting in increased risk of new onset diabetes, all-cause and cardiovascular mortality and graft failure. Immunosuppressants (ISN) may cause dyslipidemia and weight gain, but effects are class specific. Calcineurin inhibitors increase obesity; however the role of newer ISN, such as mTOR inhibitors on weight gain after HT remains unknown. We assessed the effect of tacrolimus (TAC) versus sirolimus (SRL) ISN on body weight post-HT.

*Methods: This was a tri-site Enterprise institution, retrospective, cohort study of adult post-HT patients on TAC or SRL from 1/2009 to 8/2018. Weight and clinical status were assessed at 1, 3, and 5 years post HT. If a temporary switch between TAC and SRL occurred the patient remained in the initial group unless the change was more than 6 months, then the patient’s data was truncated.

*Results: Change in weight and BMI, respectively, was less in the SRL arm compared to TAC at years 1 and 3 but not at 5 (Table 1). A 2-fold greater decline in HbA1c was seen for patients on SRL than TAC, with SRL reaching a lower HbA1c at year 1 (p=0.011). Among patients not obese (BMI > 30 kg/m²) pre-HT, obesity was more likely in those on TAC at year 1 post HT than those on SRL (24.8% vs 8.5%, p<0.001). Despite overall higher HDL, LDL, triglycerides, and total cholesterol in the SRL group, graft survival and cardiac death were similar, with a trend toward improved outcomes for SRL at 5 years (Table 2).

*Conclusions: SRL significantly decreased new onset obesity and weight gain at 1 and 3 years post-HT. SRL was associated with lower HbA1c but increased lipid biomarkers. There was no difference in graft survival or cardiac death compared to TAC. This supports the role of SRL ISN therapy in HT recipients.

Table 1: Change in weight (kg) and BMI (kg/m²)

Table 2: Survival (hazard ratio, 95% CI)

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