Risk factors for acute rejection and vasculopathy among 634 patients treated with everolimus or azathioprine

Abstract

The goal of this study is to determine the effect of multiple pre- and post-transplant risk and protective factors on the incidence of acute cardiac allograft rejection ISHLT grade 3A (AR) among 634 patients participating in a multi-center double-blind comparator-controlled trial, randomized to either everolimus (EV) or azathioprine (AZA). Univariate logistic regression modeling of effect on AR was performed for risk factors: PRA, donor age, recipient age, recipient coronary artery disease (CD), body mass index (BMI), cold ischemia time (IT), use of LVAD, and hypertension. Of these, the use of LVAD was significantly associated with AR (p = 0.002, odds ratio [OR] =-3.2, 95% CI 11.5-6.7). We also determine whether the above risk factors plus AR, mean CsA trough, mean steroid dose, creatinine level >200umol/mL, triglyceride 4.5 mmol/L, cholesterol 6.2 mmol/L, CMV, statin, ACE inhibitor, or calcium channel blockers (CCB) influenced the subsequent occurrence of IVUS-defined cardiac allograft vasculopathy (CAV) at one year (y), an endpoint studied because of its value as a surrogate for survival and MACE at 5 y after transplant. CAV was defined as an increase in maximal intimal thickness of 0.5 mm or more in any segment studied at both baseline and 1 y. Among the 211 patients with baseline and 1 y IVUS, there were too few patients with CMV or without statin use to determine whether these factors affected CAV. AR, and choice of statin were not risk factors for the occurrence of CAV. Of the risk factors analyzed donor age >50 y ((p = 0.005, OR = 3.6, CI = 1.5-9.0) was associated with increased risk of CAV as was recipient CD (p = 0.04, OR = 1.83, CI = 1.02-3.25)