Impact of tacrolimus and mycophenolate mofetil regimen versus a conventional therapy with steroids on cardiovascular risk in liver transplant patients

Clinical Transplantation 2015 Aug;29(8):667-77.

Aims
To evaluate the impact of a steroid-free regimen with tacrolimus and mycophenolate mofetil (modified therapy) versus a standard regimen of tacrolimus and steroids on the cardiovascular risk score of liver transplant recipients.

Interventions
Patients received either a steroid-free regimen with tacrolimus and mycophenolate mofetil (MMF) (modified regimen) or a conventional regimen with tacrolimus and steroids (standard regimen)

Participants
Adult (18-70 years) recipients of a primary liver transplant

Outcomes
The primary endpoint was estimated cardiovascular risk score at 10 years assessed at baseline and at 12 months post-transplantation. Secondary endpoints included prevalence of new-onset CVRFs, renal function, graft rejection, opportunistic infection rate and patient and graft survival.

Follow-up
1 year

CET Conclusions
This multicentre trial from Spain randomised patients to standard immunosuppression (Tac and steroids tapered to 6 months) or a modified steroid-free regimen of Tac and MMF. The authors claim “trends” towards a lower cardiovascular risk score (the primary endpoint) and improved renal function at 1 year. The choice of primary endpoint for this study is puzzling – it uses the Framingham risk calculator for 10-year cardiovascular risk (modified for the Spanish population). The use of a predictive risk score as a surrogate primary endpoint is unusual, especially as the risk score is only moderately predictive at best for risk in the liver transplant population (Liver Transpl. 2006;12(3):394-401). The power calculation is based upon a 3% difference between groups in this score, allowing for a 15% dropout rate. In reality, around 50% patients in each group failed to complete the study meaning that it is likely underpowered. None of the recorded differences (either in FRS or renal function) are statistically significant, meaning that no useful conclusions can be drawn from this trial.

Jadad score
2

Data analysis
Available case analysis

Allocation concealment
No

Trial registration
None

Funding source
Industry funded