Change in Maximum Intimal Thickness with Everolimus-Based Immunosuppression after Heart Transplantation in Patients at Increased Risk of Cardiac Allograft Vasculopathy

Abstract

Purpose Heart transplant (HTx) patients (pts) on everolimus(EVR) have less change in maximum intimal thickness (MIT) over 12 m in the A2310 and B253 studies compared to pts on mycophenolate mofetil (MMF) or azathioprine (AZA). In A2310 this benefit was also seen in distinct pt subpopulations at increased risk of cardiac allograft vasculopathy (CAV). The purpose of the current study was to determine the effect of EVR on MIT change in the B253 study. Methods and Materials B253 was a randomized, 24m (12m double-blind), multicenter study comparing fixed-dose EVR (1.5mg or 3mg/day) to AZA (1-3mg/kg/day) with cyclosporine (CsA) and corticosteroids in 634 pts. The IVUS substudy included 211 pts. MIT was analyzed retrospectively for pt subgroups divided by age, gender, presence of diabetes, presence of donor disease (MIT≥0.5 mm at baseline (BL)), and based on Time-normalized lipid profiles. Results were compared to results from A2310. Results As in A2310, average MIT change from baseline to 12m was smaller in the EVR 1.5mg arm of study B253 for pts who were ≥50 years, male, diabetic, had donor disease, high triglycerides, or low HDL ( Table ). MIT change in pts with high total cholesterol was comparable in EVR 1.5mg and AZA, whereas in A2310 it had been smaller for the EVR group ( Table ). Conclusions HTx subgroups at increased risk of CAV treated with EVR in study B253 had less increase in MIT. Although EVR is known to raise lipid levels, there was either less or comparable change in MIT with EVR. These results confirm the findings from study A2310. Mean change in MIT (mm) from baseline to M12 Study B253 Study A2310 Baseline characteristic EVR 1.5mg (n=88) AZA (n=101) EVR 1.5mg (n=70) MMF (N=72) Age ≥ 50 years 0.04 0.15 0.03 0.08 Male gender 0.03 0.11 0.03 0.07 Diabetes 0.06 0.09 0.04 0.08 Donor disease -0.10 -0.05 0.03 0.09 Time-normalized lipids categorized by AHA classification EVR 1.5mg AZA EVR 1.5mg MMF High total cholesterol 0.05 0.06 0.04 0.15 Low HDL-C 0.02 0.05 0.02 0.10 High triglycerides 0.04 0.13 0.03 0.10