Favorable results of 24 month study of everolimus vs. AZA presented
Late breaking trial data examining intravascular ultrasound (IVUS) and treatment benefits in cardiac allograft vasculopathy (thickening of arterial walls) were presented yesterday at the 24th Annual Meeting of the International Society for Heart and Lung Transplantation.
One-year vasculopathy, as defined by an increase in Maximal Intimal Thickness (MIT) of > 0.5mm by intravascular ultrasound was shown to be predictive of 5-year clinical events. This data was presented by Jon Kobashigawa, MD, UCLA Medical School, during the session entitled "Multi-Center Intravascular Ultrasound Validation Study Among Heart Transplant Recipients: Outcomes after 5 years."
Patients with first-year change in MIT ³ 0.5 mm compared to those patients with MIT < 0.5mm had higher incidence of death or graft loss (20.8% vs. 5.9%, p=0.007), more Non-Fatal cardiac events, or more newly occurring angiographic luminal irregularities (65.2% vs. 32.6%, p=0.004).
In a second presentation, Randall Starling, MD, of the Cleveland Clinic Foundation, described the favorable effect of the proliferation signal inhibitor everolimus on cardiac allograft vasculopathy, and its concomitant reduction in acute rejection rates, is maintained through 24 months.
In this 634-patient study conducted in 54 centers worldwide, prospective analysis of the IVUS-population (matched analysis, n=149) was performed. This study, using rigorous IVUS techniques, revealed that the early findings of attenuation of development of intimal thickening by using everolimus remained even on analysis of 2 year end-points.
Dr. Javier Segovia, Clinic Puerta de Hierro, Madrid, reported in a third study that sirolimus, another proliferation signal inhibitor, reduced coronary lesions of patients with established cardiac allograft vasculopathy. In this small trial, there was suggestion of a plaque regression in those treated as compared with conventional immunosuppressive regimens.
During the panel discussion, following the presentations, chaired by Mandeep Mehra, MD, Ochsner Clinic Foundation, New Orleans, Dr. Mehra discussed the importance of the choice of using a threshold of intimal thickness of > 0.5mm versus > 0.3mm (as used in the MMF versus AZA study presented earlier in the congress). The panel responded that an increase of at least 0.5mm has been more robustly validated as a clinically relevant measurement and represents an "unequivocal" threshold of abnormality.
Panelist Javier Segovia, MD, added that "a cut-off of 0.3mm MIT may be too close to the limit of precision of this technique (0.2mm). Furthermore, 0.3mm MIT is sometimes observed in the donor heart early after transplantation."
The value of IVUS end-points as a valid surrogate in the context of a therapeutic intervention was also debated. While most panel members agreed that discrepancies exist in the data to date, clinical decisions cannot be delayed for several years until the long term evidence is available.
Dr. Starling, co-moderator for the session, stated in conclusion, "What is striking in the results presented today is that the direction and magnitude of all intravascular ultrasound measurements were concordant in favor of everolimus as a preventative strategy and sirolimus in the regression of cardiac allograft vasculopathy."
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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