Does the Dose of Mycophenolate Mofetil Impact Outcome after Heart Transplantation?

Abstract

Mycophenolate mofetil (MMF) is an anti-proliferative agent that is used in heart transplantation (HTx). The multicenter randomized trial of mycophenolate published in Transplantation in 1998 demonstrated that MMF had a survival benefit. The average dose of MMF was 2.8 g/day. It is not clear whether lower doses of MMF also have benefit in terms of control of rejection as well as other outcomes. Between 2010 and 2018, we assessed 240 HTx patients and divided them into categories of MMF dosing in the first year after HTx. The average daily dose of MMF was obtained for all patients in the first year, with an average of 10 MMF dose levels obtained over the first year. Patients were divided into groups based on receiving an average daily dose of <500 mg MMF/day, 500-1000 mg/day, 1001-1500 mg/day, 1501-2000 mg/day, and >2000 mg/day. Endpoints included 1-year survival, 1-year freedom from cardiac allograft vasculopathy (CAV), 1-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke), and 1-year freedom from rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody mediated rejection (AMR)). Patients treated with <500 mg MMF/day and >2000 mg MMF/day had a trend toward decreased freedom from ATR. There was no difference in outcome between all groups in terms of 1-year survival, freedom from CAV, freedom from NF-MACE, and freedom from ACR and AMR. The average daily dose of MMF in the first year after HTx does not appear to have an impact on outcome. Longer follow-up will be necessary to assess whether MMF dosing correlates to long-term complications such as CAV. Larger number of patients will be needed to confirm these findings.