Purpose: 24-month (M) results of a randomized, open-label, multinational study (A2310) comparing efficacy and safety of everolimus (EVR) and mycophenolate mofetil (MMF) in de novo heart transplant recipients (HTxR) are available. HTxR in North America (NA) compared to Overall (OVR) had increased diabetes, hypertension, hyperlipidemia, high body mass index; greater ventricular assist device use and less induction therapy. We examined efficacy and adverse events (AEs) for NA HTxR in the A2310 study.
Methods: HTxR were randomized to 1.5mg (N=155) vs 3mg/day (N=99) EVR (goal C0: 3-8 or 6-12ng/mL) w/reduced-dose cyclosporine (rdCsA) or 3g/day MMF w/standard-dose CsA (sdCsA) (N=157) + steroids. The EVR 3mg arm was prematurely terminated due to high mortality. The 24M analysis assessed composite efficacy failure (CEF) and AEs.
Results: 48% NA HTxR (vs. 34% OVR) did not receive induction; and 17% NA (vs. 29% OVR) received thymoglobulin. In all HTxR at 24M, EVR 1.5mg was comparable to MMF for CEF, but inferior for renal function (Table). The incidence of AEs was lower in NA HTxR (EVR/MMF) vs OVR HTxR: neutropenia (5.3%/8.3% vs 17.9%/40.3%); hyperlipidemia (11.8%/5.8% vs 37.3%/26.9%); edema (48.7%/47.4% vs 57.7%/57.1%) & CMV infection (5.3%/16.0% vs 7.2%/21.6%).
|Parameter, n (%)||EVR 1.5mg (N=155)||MMF (N=157)|
|Composite efficacy failure (CEF)||54 (34.8)*||65 (41.4)|
|Acute rejection with hemodyamic compromise||8 (5.2)||10 (6.4)|
|BPAR ≥ 3a (2R)||38 (24.5)||46 (29.3)|
|Death||12 (7.7)||12 (7.6)|
|Graft loss/re-transplant||3 (1.9)||4 (2.5)|
|Loss to follow-up||3 (1.9)||8 (5.1)|
|Mean eGFR (MDRD), mL/min/1.73²||58.7**||65.3|
Conclusion: Despite differences in baseline demographics in NA HTxR, especially less frequent induction, de novo use of EVR 1.5mg + rdCsA has comparable efficacy to MMF + sdCsA. EVR 1.5mg or MMF was better tolerated in NA HTxR vs the OVR population, perhaps due to differences in induction therapy.
Kobashigawa, J.: Grant/Research Support, Novartis Pharmaceuticals, Other, Novartis Pharmaceuticals, Data Safety Monitoring Board. Pauly, D.: Grant/Research Support, Novartis Pharmaceuticals. Ross, H.: Other, Novartis Pharmaceuticals, Principal Investigator. Kfoury, A.: Grant/Research Support, Novartis Pharmaceuticals. Van Bakel, A.: Grant/Research Support, Novartis Pharmaceuticals. Patel, D.: Employee, Novartis. Wiland, A.: Employee, Novartis. Lopez, P.: Employee, Novartis. Balfour, A.: Employee, Novartis. Starling, R.: Grant/Research Support, Novartis. Eisen, H.: Grant/Research Support, Novartis.
To cite this abstract in AMA style:Kobashigawa J, Pauly D, Ross H, Kfoury A, Bakel AVan, Patel D, Wiland A, Lopez P, Balfour A, Starling R, Eisen H. North American Results from the Multicenter Randomized Trial of Everolimus vs Mycophenolate Mofetil in Heart Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/north-american-results-from-the-multicenter-randomized-trial-of-everolimus-vs-mycophenolate-mofetil-in-heart-transplantation/. Accessed May 27, 2020.
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