Objectives: A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcomes after kidney transplant. We hypothesized that a high intrapatient variability of tacrolimus exposure after heart transplant may be associated with cardiac allograft vasculopathy as a determinant of long-term survival of heart transplant recipients. Materials and Methods: Eighty-six heart transplant recipients were included. Patients underwent coronary angiography at years 1 and 4 after transplant and were divided according to low and high intrapatient variability of tacrolimus exposure, with the median variability as cut-off. The primary outcome was the association between tacrolimus intrapatient variability and the progression of cardiac allograft vasculopathy score between years 1 and 4. Secondary outcome was this association with acute cellular rejection. Results: There was no significant difference in the proportion of patients with high tacrolimus intrapatient variability in the group that progressed to higher grades of cardiac allograft vasculopathy (n = 15) versus the group without progression (n = 71) at 4-year follow-up (60.0% vs 47.9%; P =.57). There was no significant difference in the proportion of patients with high tacrolimus intrapatient variability between the 58 patients with 1 or more acute cellular rejection episodes and the 28 patients without rejection (51.7% vs 46.4%; P =.82). Conclusions: A high intrapatient variability in tacrolimus exposure does not appear to influence heart transplant outcomes, unlike its influence on kidney transplant function. A higher immunosup - pression exposure after heart transplant, including the use of prednisone often in a combination of 3 immunosuppressive drugs, may protect against the effects of high intrapatient tacrolimus variability.

Additional Metadata
Keywords Acute cellular rejection, Immunosuppression
Persistent URL dx.doi.org/10.6002/ect.2016.0366, hdl.handle.net/1765/107341
Journal Experimental and Clinical Transplantation
Citation
Shuker, N.M, Bouamar, R, Hesselink, D.A, van Gelder, T, Caliskan, K, Manintveld, O.C, … Constantinescu, A.A. (2018). Intrapatient variability in tacrolimus exposure does not predict the development of cardiac allograft vasculopathy after heart transplant. Experimental and Clinical Transplantation, 16(3), 326–332. doi:10.6002/ect.2016.0366