Everolimus for the Prevention of Allograft Rejection and Vasculopathy in Cardiac-Transplant Recipients

Eisen, Howard J.; Tuzcu, E. Murat; Dorent, Richard; Kobashigawa, Jon A.; Mancini, Donna; Kaeppler, Hannah A. Valantine-von; Starling, Randall C.; Sørensen, Kasper; Hummel, Manfred; Lind, Joan M.; Abeywickrama, Kamal; Bernhardt, Peter

doi:10.1056/nejmoa022171

Cited by 1,088 publications

(780 citation statements)

References 30 publications

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“…It has been reported that immunosuppressive treatment limited the progression of carotid arteriopathy in patients with SLE (3). The predominance of T cells in the arterial inflammatory infiltration observed in this patient and the histopathologic similarity to transplantassociated arteriopathy suggest that immunosuppressive treatment specifically targeting T lymphocytes or approaches aimed at interfering with peripheral T cell recruitment might be particularly effective in the prevention and treatment of this specific complication of SLE (17). 912 CONEN ET AL…”

Section: Discussionmentioning

confidence: 82%

Acute occlusive large vessel disease leading to fatal stroke in a patient with systemic lupus erythematosus: Arteritis or atherosclerosis?

Conen¹,

Jeanneret²,

Hecker³

et al. 2006

Arthritis & Rheumatism

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A woman with a history of systemic lupus erythematosus presented with extensive bilateral strokes due to acute inflammatory, occlusive large vessel disease affecting several aortic branches including the carotid, subclavian, renal, and iliac arteries. We quantitatively characterized the arterial inflammation in this patient and compared it with the inflammatory infiltrates from 22 patients with conventional atherosclerosis. Profound histomorphologic differences from conventional atherosclerosis (predominance of CD8-positive lymphocytes, relative absence of macrophages, no ectopic neovascularization, no signs of plaque hemorrhage, concentric instead of eccentrical stenosis) suggest that this patient's accelerated arteriopathy was precipitated by pathogenic events other than conventional atherosclerosis.

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Section: Discussionmentioning

confidence: 82%

Acute occlusive large vessel disease leading to fatal stroke in a patient with systemic lupus erythematosus: Arteritis or atherosclerosis?

Conen¹,

Jeanneret²,

Hecker³

et al. 2006

Arthritis & Rheumatism

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show abstract

“…Other publications quoted the mortality from cardiovascular disease between 1.5 and 3% of the total number of patients alive at 1 year. In heart transplant recipients, the main causes for late secondary organ loss are vascular diseases and their complications (Abbasoglu et al, 1997;Pruthi et al, 2001;Rabkin et al, 2001;Eisen et al, 2003) It is true that classical cardiovascular risk factors like hypertension, obesity, diabetes mellitus and so on were also responsible for these incidences.…”

Section: Discussionmentioning

confidence: 99%

The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study

Akoglu

Schrott²,

Bolouri

et al. 2007

Eur J Clin Nutr

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Objective: Hyperhomocysteinemia is a described risk factor of cardiovascular diseases. The aim of this study was the treatment of hyperhomocysteinemia in liver transplant recipients with L-5-methyltetrahydrofolate (L-5-MTHF; 1 mg) vs folic acid (1 mg) vs placebo in a double-blind placebo-controlled study and to compare the relative responsiveness of these patients to L-5-MTHF and folic acid. Subjects/Methods: Patients were recruited from Hepatology-Transplantation-Unit at Johann Wolfgang Goethe-University, Frankfurt. Sixty patients were included in this study and 12 patients dropped out for different reasons. The patients were treated over 8 weeks with supplemental L-5-MTHF or folic acid or placebo. Serum homocysteine (HCY) was analyzed with highperformance liquid chromatography (HPLC) beside routine lab tests. Results: We observed only a significant decrease of total serum HCY in the L-5-MTHF group during the study period (at week 0: 1577.7 mM; after 8 weeks treatment: 9.4172.6 mM, Po0.001). There was no significant decrease of total serum HCY neither in the folic acid group nor in the placebo group. Conclusion: The effects of L-5-MTHF are significantly more potent than folic acid itself. Therefore, lowering serum HCY in liver transplant recipients is effective with L-5-MTHF.

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“…Other publications have given the mortality from CVD as between 1.5 and 3% of the total number of patients alive after one year. In heart transplant recipients, the main causes for late secondary organ loss are vascular diseases and their complications (Abbasoglu et al, 1997;Pruthi et al, 2001;Rabkin et al, 2001;Eisen et al, 2003). Classical cardiovascular risk factors such as hypertension, obesity, diabetes mellitus etc., were held responsible for these data.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the methylenetetrahydrofolate reductase gene are determinant for vascular complications after liver transplantation

et al. 2007

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Objective: The aim of this study was to evaluate the role of the C677T-MTHFR (methylenetetrahydrofolate reductase)-polymorphism (CC, CT and TT) for vascular complications in liver transplant recipients. Design: Retrospective study. Setting: Hepatology-Transplantation-Unit, Johann Wolfgang Goethe-University, Frankfurt am Main. Subjects: 48 liver transplant recipients were included, no dropouts. Methods: MTHFR polymorphism was detected by PCR amplification and digestion with Hinfl restriction enzyme. Vascular complications after liver transplantation were detected from the patients' records. The total serum homocysteine (HCY) was analyzed with high-pressure liquid chromatography. Results: In the wild-type group (CC), the HCY levels were slightly high (14.071 mM). Among the patients with the CT polymorphism, the HCY values were elevated (22.573 mM). In the homozygous TT group, there was a significant increase (31.276 mM, Po0.01) of the HCY values. The percentage of vascular complications was higher in the heterozygous CT (47%) and homozygous TT (62.5%) group compared with wild-type CC (21%). Patients with a homozygous TT genotype of the MTHFR polymorphism with a vascular complication had a highly significant elevated HCY level compared to the other genotype groups, both with and without any vascular complications (Po0.001). Recipients with an elevated HCY and the TT polymorphism have a higher probability of developing a vascular complication after transplantation (odds ratio: 4.3 and 11.0; 95% confidence interval: 1.15, 12.25 and 1.41, 85.24). Conclusions: The C677T polymorphism in the MTHFR gene and subsequent elevation of the total serum HCY is significantly associated with an increased incidence of vascular complications in liver transplant recipients. Sponsorship: None.

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Everolimus for the Prevention of Allograft Rejection and Vasculopathy in Cardiac-Transplant Recipients

Abstract: Everolimus was more efficacious than azathioprine in reducing the severity and incidence of cardiac-allograft vasculopathy, suggesting that everolimus therapy may alleviate this serious problem.

Cited by 1,088 publications

References 30 publications

Acute occlusive large vessel disease leading to fatal stroke in a patient with systemic lupus erythematosus: Arteritis or atherosclerosis?

Acute occlusive large vessel disease leading to fatal stroke in a patient with systemic lupus erythematosus: Arteritis or atherosclerosis?

The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study

Polymorphisms in the methylenetetrahydrofolate reductase gene are determinant for vascular complications after liver transplantation

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