Conversion to Sirolimus as Primary Immunosuppression Attenuates the Progression of Allograft Vasculopathy After Cardiac Transplantation

Abstract

Background-We investigated the potential of conversion to sirolimus (SRL) as a primary immunosuppressant in attenuating cardiac allograft vasculopathy progression. Methods and Results-Twenty-nine cardiac transplant recipients were converted to SRL 3.8Ϯ3.4 years after transplantation with complete calcineurin inhibitor (CNI) withdrawal. Secondary immunosuppressants (azathioprine or mycophenolate) and steroids remained unchanged. Forty patients (controls) 4.8Ϯ4.0 years from transplantation were maintained on CNIs. Three-dimensional intravascular ultrasound studies were performed at baseline and 12.1Ϯ2.6 months later.

Canadian Cardiovascular Society Consensus Conference update on cardiac transplantation 2008: Executive Summary

“…Attenuation of the progression of ACAD has been seen in patients with established ACAD in whom sirolimus was added to CNI therapy (91). Similar results were seen in another study (92) in which rapamycin was used to replace CNI therapy; however, the incidence of rejection in the absence of CNI increased significantly. Based on these findings, many centres consider adding rapamycin in patients with documented ACAD.…”

The Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Recipients: One-Year Results of a Scandinavian Randomized Trial

“…The pathology slides were reported at each center as per the clinical reports in an unblinded fashion and the majority of BPAR episodes occurred within the first 150 days after randomization (17). The incidence of biopsy proven acute rejection (BPAR) in the IVUS study population was 76.6% in the everolimus group versus 62.5% in the cyclosporine group (p ¼ 0.14).…”

“…can attenuate the progression of CAV after HTx (17,18). However, there have only been two previous trials investigating the effect of everolimus on CAV progression among de novo HTx recipients (6,7), and both studies investigated the effect of such therapy in combination with either full-dose or reduced CNI exposure.…”

Myocardial perfusion imaging for cardiac allograft vasculopathy assessment: Evidence grows, but questions remain

“…1 Risk factor modification and early therapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus may attenuate CAV progression. 2,3 Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) are useful for focal lesions but suboptimal in advanced disease because of diffuse disease, poor targets, and high restenosis rates. Retransplantation is effective, but raises ethical concerns, is severely hampered by organ shortage, and requires planning and waiting during which time clinical events can occur.…”

“…While late CAV is an important contributor to mortality, CAV can also progress rapidly early after transplant, and the benefit of tailored immunosuppression for CAV is most effective when initiated within the first 2 years after transplantation. 3,15 The role of SPECT in early CAV diagnosis remains uncertain.…”