Transplant Trial Watch

Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Heart Transplant Recipients.

Arora S, Andreassen AK, et al.

Circ Heart Fail. 2018; 11(9):e004050.

To evaluated whether initiation of everolimus and early cyclosporine elimination can reduce cardiac allograft vasculopathy (CAV) development in heart transplantation recipients.

Patients were randomized to everolimus with complete cyclosporine withdrawal 7 to 11 weeks after heart transplantation or standard cyclosporine-based immunosuppression. Intravascular ultrasound recordings were obtained at baseline, 12 and 36 months.

115 de novo heart transplantation recipients were randomized. Seventy-six patients had matched intravascular ultrasound examinations at baseline, 12 and 36 months.

Effect of everolimus initiation and CNI elimination on CAV at 12 and 36 months assessed by assessing percent atheroma volume (PAV) and total atheroma volume (TAV) (as alternative end points to maximal intimal thickness) as well as angiographic data. Inflammatory markers were measured in parallel. Plaque morphology was qualitatively assessed by virtual histology analysis at 12 and 36 months post randomization.

36 months.

CET Conclusions
This was an open-label, multicentre RCT in cardiac transplantation. Unfortunately, only 66% of those randomised went on to have matched intravascular ultrasound at both 12 and 36 months, the most common reason for dropout was logistical/technical issues. Patients in the everolimus arm had a greater risk of progression in cardiac allograft vasculopathy (CAV, as defined on intravascular ultrasound), and in multivariate analysis everolimus was an independent predictor of CAV progression, along with recipient sex and donor age. Worryingly there was a significantly higher risk of rejection graded ≥2R in the everolimus group (41% versus 13%), but there were no cases of humoral rejection or rejection with haemodynamic compromise and there were slightly more deaths in the ciclosporin arm (7 versus 3). Angiographic assessment of CAV progression did not show a significant difference between the two study arms, possibly due to the short follow-up period.

Jadad score

Data analysis
Available case analysis

Allocation concealment

Quality notes
Previously assessed as Andreassen AK, Andersson B, et al. Am J Transplant; 14:1828-38, 2014.

Trial registration - NCT01266148.

Funding source
Industry funded