Optimizing Medication Dosing After Heart Transplantation

Volume 22, Issue 4

Heart transplantation remains the gold standard surgical treatment modality for end-stage heart failure, with current median survival rates exceeding 13 years. To avoid the competing risks of infection and allograft rejection, patients must take an expertly balanced regimen of immunosuppression for the rest of their lives. Drug-related adverse events must also be carefully managed, as patients often take 2 to 3 medications that suppress the immune system.

Mycophenolate mofetil is one of the cornerstone medications that patients take long term after heart transplant surgery. Unlike tacrolimus, which is titrated according to plasma concentrations, mycophenolate is given as a flat dose of 2 to 3 grams per day in 2 divided doses. Despite this relatively straightforward dosing strategy, a significant number of patients will still experience either rejection or a drug-related side effect on mycophenolate. Furthermore, no studies have directly compared 2 g/day vs 3 g/day of mycophenolate in the current era of heart transplantation.

In this week’s issue of Talking Therapeutics, we look at a new study evaluating 2 mycophenolate dosing regimens after heart transplant surgery.

Point 1: Dose Matters

In the study, for which I was co-first author, we evaluated 168 patients who received either a 2 g/day or 3 g/day dose of mycophenolate after heart transplant. Freedom from neutropenia, which is the most serious side effect of mycophenolate early after transplant, was lower in high-dose group compared with the low-dose group (57% vs 73%, P = .03).

Freedom from cellular rejection was similar between groups; however, low-dose mycophenolate was associated with more severe grades of cellular rejection during the first month (hazard ratio [HR] 3.47, 95% confidence interval [CI] 1.09 to 11.08, P = .03), but less neutropenia between 1 month and 6 months (HR 0.54, 95% CI 0.29 to 1.00, P = .05). 

Point 2: No 'One Dose Fits All'

The results of this paper point to an interesting paradigm. Based on our findings, it seems neither regimen is superior, but rather, the timing of the dosing is the most important feature.

High-dose mycophenolate appears superior within the first month, as this regimen was associated with a reduced risk of more severe rejection episodes. After the first month, the low-dose regimen was superior given the lower risk of neutropenia. Hence the best regimen for mycophenolate after heart transplant appears to be 3 g/day for 1 month, followed by 2 g/day after 1 month.