The CECARI Study: Everolimus (Certican®) Initiation and Calcineurin Inhibitor Withdrawal in Maintenance Heart...

Area of Science:

• Nephrology
• Cardiology
• Transplantation

Background:

• Calcineurin inhibitors (CNIs) are standard immunosuppressants post-heart transplant but can cause renal insufficiency.
• Renal impairment is a significant long-term complication in heart transplant recipients.
• Exploring alternative immunosuppressive strategies is crucial for improving patient outcomes.

Purpose of the Study:

• To evaluate the efficacy of everolimus with CNI withdrawal versus continued CNI-based immunosuppression on renal function in heart transplant recipients.
• To assess the safety and tolerability of everolimus in this patient population.

Main Methods:

• A 3-year, open-label, multicenter study randomized 57 heart transplant recipients with renal insufficiency to everolimus with CNI withdrawal or continue CNI therapy.
• The primary endpoint was the change in measured glomerular filtration rate (mGFR) from baseline to year 3.
• Safety endpoints included mortality, major adverse cardiovascular events, acute rejection, and adverse events.

Main Results:

• The primary endpoint, change in mGFR, did not differ significantly between groups at 3 years (p=0.18).
• An on-treatment analysis showed a statistically significant improvement in mGFR in the everolimus group (p=0.047).
• The everolimus group experienced a higher incidence of nonfatal adverse events (96.6% vs 57.1%) and drug discontinuation (34.5%) due to adverse events.

Conclusions:

• CNI withdrawal with everolimus did not demonstrate a significant benefit in renal function compared to continued CNI therapy in the intention-to-treat analysis.
• Poor adherence to everolimus therapy may have confounded the results, potentially masking a renal benefit.
• Alternative immunosuppression strategies require careful consideration of efficacy and tolerability in heart transplant recipients with renal insufficiency.