Mycophenolate mofetil for secondary prevention of cardiac allograft vasculopathy: Influence on inflammation and progression of intimal hyperplasia

Background: Cardiac allograft vasculopathy (CAV) remains the single most important complication impairing long-term survival after heart transplantation (HTx). Intimal hyperplasia as a response to immunologic and non-immunologic injury is involved,in the pathogenesis. Because improved immunosuppressive properties with mycophenolate mofetil (MMF) have been shown within the first year, beneficial effects on intimal hyperplasia and systemic inflammation might be found late after HTx as well. Methods: After a baseline examination with intravascular ultrasound (IVUS, volumetric assessment) 30 patients (2.0 +/- 1.1 years post-HTx) were prospectively randomized to receive either MMF (2 g/day) or to continue with azathioprine (AZA) as part of a triple immunosuppression protocol with cyclosporine and prednisolone. Markers of systemic inflammation and changes in vascular geometry were evaluated by IVUS after 1 year of follow-up. Results: With regard to inflammation, significantly lower values were found for high-sensitive C-reactive protein (CRP) in the MMF group (AZA 1.8 +/- 1.2 mg/liter. vs MMF 1.0 +/- 4.1 mg/liter, p = 0.02). Tumor necrosis factor (TNF)-alpha, interleukin (IL)10, IL-6 and transforming growth factor (TGF)-beta did not differ between the groups. IVUS revealed no significant differences between groups. There was a weak trend toward a larger increase in plaque volume (AZA 13 +/- 43 mm(3) vs, MMF 27 +/- 41 mm(3), p = 0.33), whereas MMF-treated patients tended to show a small increase in vessel dimensions (AZA +10 +/- 63 mm(3) vs MMF +50 +/- 87 mm(3), p = 0.17). Conclusions: Changing immunosuppression from a standard AZA-based regimen to MMF resulted in a decrease in systemic inflammatory activity as indicated by levels of high-sensitive CRP. However, progression of intimal hyperplasia did not differ significantly, and the weak trend toward vascular enlargement could indicate some influence on vascular geometry. J Heart Lung Transplant 2004;23:61-66.