Benefit of Tacrolimus/Myocophenolate To Reduce Cardiac Allograft Vasculopathy after Heart Transplantation

Abstract

Purpose Over the past 2 decades, the development of cardiac allograft vasculopathy (CAV) in heart transplant (HTx) patients (pts) has not significantly changed. Randomized clinical trials comparing cyclosporine (CSA) and tacrolimus (TAC)-based regimens have not demonstrated significant differences in CAV development, but followup time has been short (2 years). Mycophenolate (MMF) has been shown in a large randomized trial to decrease first year intimal thickening in HTx pts compared to azathioprine (both groups with CSA). TAC/MMF vs CSA/MMF in the 3-Arm Trial significantly reduced rejection but followup time was insufficient to assess for CAV. To assess for a possible CAV benefit, we reviewed our pts maintained on TAC/MMF vs CSA/MMF for development of CAV over 5 years. Methods and Materials Between 1994-2010, we evaluated 728 HTx pts. CAV was defined as any angiographic stenosis ≥30%. Pts were divided into those maintained on CSA/MMF(n=273) and TAC/MMF(n=455). 5 year actuarial survival, freedom from CAV and freedom from non-fatal major adverse cardiac events (NF-MACE) were assessed. Results Pts treated with TAC/MMF vs CSA/MMF had significantly greater freedom from CAV(81% vs 74%, p=0.044). Survival and NF-MACE were similar ( table ). CAV severity according to the ISHLT CAV nomenclature was similar in CSA/MMF vs TAC/MMF (CAV1: 59% vs 65%, p=0.57; CAV2: 19% vs. 14%, p=0.52; CAV3: 22% vs 21%, p=0.92). Conclusions TAC/MMF compared to CSA/MMF appears to have a beneficial effect in decreasing the incidence of CAV post-HTx. Outcomes CSA/MMF (n=273] TAC/MMF (n=455) p-value 5-Year Actuarial Survival 78% 83% 0.133 5-Year Freedom from CAV 74% 81% 0.044 5-Year Freedom from NF-MACE 84% 84% 0.868 1-Year Freedom from Any-Treated Rejection 88% 85% 0.349