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Abstract

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 immunosuppression 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.

A Systematic Review of Adherence to Immunosuppression among Pediatric Heart Transplant Patients

“…Per the International Society for Heart and Lung Transplantation (ISHLT) data, rejection within the first year is associated with CAV development [ 32 ]. However, in adults, tacrolimus intrapatient variability was not associated with cardiac allograft vasculopathy [ 33 ]. Pediatric patients with cardiac allograft vasculopathy have a 50% allograft survival rate at nearly three years [ 34 ].…”

The Role of Intra-Patient Variability of Tacrolimus Drug Concentrations in Solid Organ Transplantation: A Focus on Liver, Heart, Lung and Pancreas

“…In contrast, Shuker et al reported, in an 86 HT recipient cohort co-treated with rATG induction, MMF and CS, the lack of a relationship between IPV of TAC C min and the progression of CAV between two coronary angiographies performed at one and four years post-transplantation, and acute rejection. It is noteworthy that IPV was evaluated after six months, and that the median IPV was low (17.7%), suggesting a very high adherence in the population study [20]. A less commonly explored IPV marker, the TTR has been recently evaluated by Baker and colleagues.…”

Overcoming Compensatory Mechanisms toward Chronic Drug Administration to Ensure Long-Term, Sustainable Beneficial Effects

“… 54 In contrast, the intra-patient variability in tacrolimus exposure had no effect on the outcome of heart transplants. 55 Intra-patient variation in the area under the curve for plasma etoposide concentration versus time following intravenous drug administration is minimal, but increases following oral administration, where high variation in drug toxicity is seen. Mean etoposide bioavailability was 64% in this study, showing both inter- and intra-patient variability.…”