Late-Breaking Clinical Trial: 10-Year Follow-Up of the Everolimus versus Azathioprine Multi-National Study

Purpose This study is the 10-year follow-up of a randomized double-blind prospective trial that compared everolimus (1.5 mg or 3 mg) to azathioprine. In the original study of 634 heart transplant patients, there were significantly fewer patients on everolimus who reached the 6 month composite endpoint of death, graft loss or re-transplantation, loss to followup, biopsy-proven acute rejection, or rejection with hemodynamic compromise (36.4% and 27.0%, compared to 46.0%, p<0.03). Further, a decrease in the development of cardiac allograft vasculopathy (CAV), as assessed by intravascular ultrasound (IVUS) at 12 months, was observed in the everolimus groups compared to those on azathioprine. The purpose of this study is to assess for the clinical outcome of the early treatment of everolimus vs azathioprine at 10-years and to assess whether first-year intravascular ultrasound (IVUS) predicts long-term clinical outcome at 10-years. Methods This 10-year follow-up study included 364 patients (57% of the original patients) with 116 and 124 patients assigned to everolimus 1.5 mg and 3 mg respectively, and 124 patients assigned to azathioprine. The first analysis includes intent-to-treat by study drug with 10-year endpoint of freedom from a composite endpoint of death, re-transplant, experiencing a coronary stent, myocardial infarction, or development of angiographic CAV. In addition, on-treatment by study drug at 10-years is analyzed for the composite endpoint, individual components of the composite endpoint, left ventricular dysfunction and non-fatal major adverse cardiac events. There were 138 patients with paired IVUS studies (at baseline and 1-year) with 54 patients having first-year change in maximal intimal thickness (MIT) >0.5mm and 84 patients without. Study endpoints for the 2 IVUS groups were the same as above. Further IVUS analysis is performed by study drug assignment and the presence of baseline donor disease. Results 10-year survival, freedom from angiographic CAV or NF-MACE by the intent-to-treat and on-treatment analyses by study drugs (everolimus vs azathioprine) will be revealed. Whether the change in first-year IVUS parameters (specifically change in MIT>0.5mm) can predict 10-year outcome (survival, angiographic CAV or NF-MACE) will also be revealed. Conclusion Findings with conclusions will be discussed at the late-breaking session. This study is the 10-year follow-up of a randomized double-blind prospective trial that compared everolimus (1.5 mg or 3 mg) to azathioprine. In the original study of 634 heart transplant patients, there were significantly fewer patients on everolimus who reached the 6 month composite endpoint of death, graft loss or re-transplantation, loss to followup, biopsy-proven acute rejection, or rejection with hemodynamic compromise (36.4% and 27.0%, compared to 46.0%, p<0.03). Further, a decrease in the development of cardiac allograft vasculopathy (CAV), as assessed by intravascular ultrasound (IVUS) at 12 months, was observed in the everolimus groups compared to those on azathioprine. The purpose of this study is to assess for the clinical outcome of the early treatment of everolimus vs azathioprine at 10-years and to assess whether first-year intravascular ultrasound (IVUS) predicts long-term clinical outcome at 10-years. This 10-year follow-up study included 364 patients (57% of the original patients) with 116 and 124 patients assigned to everolimus 1.5 mg and 3 mg respectively, and 124 patients assigned to azathioprine. The first analysis includes intent-to-treat by study drug with 10-year endpoint of freedom from a composite endpoint of death, re-transplant, experiencing a coronary stent, myocardial infarction, or development of angiographic CAV. In addition, on-treatment by study drug at 10-years is analyzed for the composite endpoint, individual components of the composite endpoint, left ventricular dysfunction and non-fatal major adverse cardiac events. There were 138 patients with paired IVUS studies (at baseline and 1-year) with 54 patients having first-year change in maximal intimal thickness (MIT) >0.5mm and 84 patients without. Study endpoints for the 2 IVUS groups were the same as above. Further IVUS analysis is performed by study drug assignment and the presence of baseline donor disease. 10-year survival, freedom from angiographic CAV or NF-MACE by the intent-to-treat and on-treatment analyses by study drugs (everolimus vs azathioprine) will be revealed. Whether the change in first-year IVUS parameters (specifically change in MIT>0.5mm) can predict 10-year outcome (survival, angiographic CAV or NF-MACE) will also be revealed. Findings with conclusions will be discussed at the late-breaking session.