Evaluation of the Major Adverse Cardiac Events Risk with Everolimus-Based Calcineurin Inhibitor Reduction or Withdrawal Regimen in Liver Transplant Recipients: 3-Year Post-Hoc Analysis of the Randomized H2304 Extension Study.
1Novartis Pharma AG, Basel, Switzerland
2Novartis Pharmaceuticals Corporation, East Hannover.
Meeting: 2016 American Transplant Congress
Abstract number: 82
Keywords: Immunosuppression, Liver transplantation, Outcome, Renal function
Session Information
Session Name: Concurrent Session: The Kidney in Liver Transplantation
Session Type: Concurrent Session
Date: Sunday, June 12, 2016
Session Time: 2:30pm-4:00pm
Presentation Time: 3:42pm-3:54pm
Location: Room 302
Purpose:
Cardiovascular disease (CVD) is one of the leading causes of death in liver transplant recipients (LTxRs). Impaired glomerular filtration rate (GFR) is a risk factor for CVD. In the 24 month (M) post-hoc analysis of the H2304 study, everolimus (EVR) with reduced tacrolimus (rTAC) or tacrolimus withdrawal (TAC-WD) provided adequate immunosuppression, improved renal function and reduced the incidence of major adverse cardiac events (MACE) compared with standard TAC (TAC-C). Here we present the post-hoc analysis of the CVD risk at 36M post LTx, from the randomized H2304 extension study.
Methods:
H2304 is a 24M, randomized, open-label, multicenter study in which LTxRs on day 30 post-Tx were randomized to receive either EVR+rTAC (n = 245), EVR+TAC-WD (n = 229) or TAC-C (n = 242). After the core study, LTxRs were followed up for additional 12M. Renal function was measured by estimated glomerular filtration rate (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD4) formula. Adverse events (AEs) associated with MACE (ischaemic heart disease, cardiac failure, sudden death and ischaemic stroke) were used to determine the CV risk of this extension study population.
Results:
Of the 716 randomized LTxRs, 282 were followed up till M36. At M36, eGFR values for TAC-WD, EVR+rTAC and TAC-C arms were 86 ± 27.4, 85.2 ± 30.5 and 70.8 ± 22.9 mL/min/1.73 m2. The cumulative incidence of MACE was lower in the TAC-WD arm (n = 3; 15.6/1000 patient-years [PY]) compared with EVR+rTAC (n = 8; 22.5/1000 PY) and TAC-C (n = 13; 59.8/1000 PY) arms. The risk of MACE was also significantly lower (P = 0.0105) in the TAC-WD arm compared with the TAC-C arm.
Conclusion:
This M36 follow-up post-hoc analysis suggests that compared with TAC-C, EVR facilitated reduction or withdrawal of TAC, provides better renal function and is associated with lower incidence of MACE.
CITATION INFORMATION: Bernhardt P, Dong G, Lopez P, Hustache G, Bader G. Evaluation of the Major Adverse Cardiac Events Risk with Everolimus-Based Calcineurin Inhibitor Reduction or Withdrawal Regimen in Liver Transplant Recipients: 3-Year Post-Hoc Analysis of the Randomized H2304 Extension Study. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Bernhardt P, Dong G, Lopez P, Hustache G, Bader G. Evaluation of the Major Adverse Cardiac Events Risk with Everolimus-Based Calcineurin Inhibitor Reduction or Withdrawal Regimen in Liver Transplant Recipients: 3-Year Post-Hoc Analysis of the Randomized H2304 Extension Study. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/evaluation-of-the-major-adverse-cardiac-events-risk-with-everolimus-based-calcineurin-inhibitor-reduction-or-withdrawal-regimen-in-liver-transplant-recipients-3-year-post-hoc-analysis-of-the-randomiz/. Accessed July 3, 2025.« Back to 2016 American Transplant Congress