Transplant Trial Watch

Association Between Renal Dysfunction and Major Adverse Cardiac Events After Liver Transplantation: Evidence from an International Randomized Trial of Everolimus-Based Immunosuppression.

Saliba F, Fischer L, et al.

Ann Transplant. 2018; 23:751-7.


Aims
A post-hoc analysis of data from an RCT of de novo liver transplant recipients examining the association between the evolution of renal function and the incidence of major adverse cardiac events over the first 2 years post-transplantation.

Interventions
Patients were randomized at 30 days post-transplant to receive: (i) everolimus [EVR] and reduced tacrolimus [EVR/rTAC], (ii) EVR with tacrolimus discontinued [TAC Elimination], or (iii) standard tacrolimus [TAC Control].

Participants
719 patients were randomized and formed the ITT population (EVR/rTAC, n=245, TAC Elimination, n=231, TAC Controls, n=243).

Outcomes
Trends in renal function from randomization to Month 24 were evaluated using eGFR values documented at each study visit (Months 1, 2, 3, 4, 5, 6, 9, 12, 18, and 24) to calculate the area under the curve (AUC). Information on major cardiac events was collected as part of adverse event reporting procedures at each study visit. The association between eGFR AUC and treatment group, and eGFR AUC as a continuous variable and the occurrence of first major cardiac event was assessed. All analyses were based on the ITT population.

Follow-up
24 months post randomization.

CET Conclusions
This post-hoc analysis investigated whether there is a relationship between renal dysfunction and the incidence of major cardiac events in de novo liver transplant recipients. Data were used from an RCT comparing everolimus/reduced tacrolimus versus everolimus/tacrolimus discontinuation versus standard tacrolimus. Major cardiac events were defined as ischemic heart diseases, cardiac failure, ischemic stroke, and sudden death. The evolution of renal function was determined according to the area under the curve (AUC) of the estimated glomerular filtration rate (eGFR) from baseline to 2 years posttransplant. The analysis included 716 patients for whom data on major cardiac events were available. It was shown that renal function was inversely related to the incidence of major cardiac events in the first 2 years posttransplant.

Jadad score
3

Data analysis
Strict intention-to-treat analysis

Allocation concealment
Yes

Quality notes
SCORE BASED ON ‒ De Simone P, Nevens F, et al. Am J Transplant; 12:3008-20, 2012.

Trial registration
ClinicalTrials.gov - NCT00622869

Funding source
Industry funded