Background: The multicenter randomized trials of everolimus have demonstrated a significant reduction in 1st Year maximal intimal thickness. It has been demonstrated from a validation study that 1st year maximal intimal thickness > 0.5 mm results in more angiographic abnormalities at 5 years after transplant. We sought to verify this finding by following our patients on everolimus at the time of heart transplant for 5 years and comparing them to age-match-sex controls.
Methods: Between 1994 and 2010, we evaluated 800 heart transplant patients and divided them into initial immunosuppression groups which included: Cyclosporine (CYA)/Mycophenolate (MMF), tacrolimus (TAC)/MMF and CYA/everolimus (EVR). Patients were followed for 5 years after heart transplantation for survival, freedom from cardiac allograft vasculopathy (CAV: any angiographic stenosis ≥ 30%, including grades of CAV), freedom from non-fatal major adverse cardiac events (NF-MACE: MI, stroke, new onset CHF, percutaneous cardiac intervention, need for defibrillator/pacemaker), and 1-year freedom from rejection.
Results: There was no significant difference in 5 year survival and freedom from CAV or NF-MACE among the 3 groups. However, review of CAV severity found no ISHLT grade 2-3 CAV in the CYA/EVR group compared to the CYA/MMF and TAC/MMF groups (0% vs 38% vs 31%) but numbers are small.
|Outcomes||CYA/MMF (N=243)||TAC/MMF (N=528)||CYA/EVR (N=29)||Log-Rank p-value|
|1-Year Freedom from Any-Treated Rejection||90%||87%||83%||0.417|
|5-Year Actuarial Survival||77%||83%||76%||0.106|
|5-Year Freedom from NF-MACE||84%||85%||83%||0.913|
|5-Year Freedom from CAV||83%||85%||93%||0.318|
|Total with CAV, n||42||79||2||–|
|CAV1, n (%)||26 (62%)||54 (69%)||2 (100%)||–|
|CAV2, n (%)||8 (19%)||13 (16%)||0 (0%)||–|
|CAV3, n (%)||8 (19%)||12 (15%)||0 (0%)||–|
Conclusion: Patients treated with proliferation signal inhibitors at the time of heart transplantation appear to develop less severe CAV compared to patients not on proliferation signal inhibitors. A larger study is warranted to confirm these findings.
Patel, J.: Grant/Research Support, Alexion Pharma. Kobashigawa, J.: Grant/Research Support, Novartis Pharmaceuticals, Other, Novartis Pharmaceuticals, Data Safety Monitoring Board.
To cite this abstract in AMA style:Patel J, Kittleson M, Rafiei M, Osborne A, Chang D, Czer L, Kobashigawa J. Severity of Cardiac Allograft Vasculopathy after Heart Transplant Is Reduced with Proliferation Signal Inhibitors [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/severity-of-cardiac-allograft-vasculopathy-after-heart-transplant-is-reduced-with-proliferation-signal-inhibitors/. Accessed January 27, 2021.
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