Increased risk of venous thromboembolism with a sirolimus-based immunosuppression regimen in lung transplantation

• Published in: The Journal of heart and lung transplantation Vol. 30; no. 2; pp. 175 - 181
• Main Authors: Ahya, Vivek N., McShane, Pamela J., Baz, Maher A., Valentine, Vincent G., Arcasoy, Selim M., Love, Robert B., Seethamraju, Harish, Garrity, Edward, Alex, Charles G., Bag, Remzi, DeOliveira, Nilto C., Vigneswaran, Wickii T., Charbeneau, Jeff, Krishnan, Jerry A., Durazo-Arvizu, Ramon, Norwick, Lourdes, Bhorade, Sangeeta
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2011; Elsevier
• Subjects: Azathioprine - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Therapy, Combination; drug toxicity; Female; Graft Rejection - immunology; Graft Rejection - prevention & control; Humans; immunosuppression; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Incidence; lung transplantation; Lung Transplantation - immunology; Male; Medical sciences; Middle Aged; mTOR (mammalian target of rapamycin) inhibitors; Prednisone - therapeutic use; Prospective Studies; Risk Factors; sirolimus; Sirolimus - adverse effects; Sirolimus - therapeutic use; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Tacrolimus - therapeutic use; venous thromboembolism; Venous Thromboembolism - epidemiology; immunosuppression; lung transplantation; mTOR (mammalian target of rapamycin) inhibitors; drug toxicity; venous thromboembolism; sirolimus; Antineoplastic agent; Sirolimus; Lung; Cardiovascular disease; Risk; Transplantation; Homotransplantation; Phlebology; Macrocycle; Venous disease; Vascular disease; Surgery; Graft; Venous thrombosis; Protein synthesis inhibitor; Cardiology; Thromboembolism; Deep vein thrombosis; Lactone; Macrolide; Antibiotic; Immunosuppression; Treatment; Risk factor; Circulatory system; Immunosuppressive agent
• ISSN: 1053-2498; 1557-3117; 1557-3117
• DOI: 10.1016/j.healun.2010.08.010

Sirolimus (rapamycin) is a potent anti-proliferative agent with immunosuppressive properties that is increasingly being used in solid-organ and hematopoietic stem cell transplantation. In addition, this drug is being investigated for treatment of a broad range of disorders, including cardiovascular disease, malignancies, tuberous sclerosis, and lymphangeioleiomyomatosis. In this study, we found an increased risk of venous thromboembolism (VTE) in lung transplant recipients treated with a sirolimus (SIR)-based immunosuppressive regimen. One hundred eighty-one lung transplant recipients were enrolled in a prospective, multicenter, randomized, open-label trial comparing a tacrolimus (TAC)/SIR/prednisone immunosuppression regimen with a TAC/azathioprine (AZA)/prednisone immunosuppressive regimen. The differences in rates of VTE were examined. There was a significantly higher occurrence of VTE in the SIR cohort [15 of 87 (17.2%)] compared with the AZA cohort [3 of 94 (3.2%)] (stratified log-rank statistic = 7.44, p < 0.01). When adjusted for pre-transplant diagnosis and stratified by transplant center, this difference remained essentially unchanged (hazard ratio for SIR vs AZA = 5.2, 95% confidence interval 1.4 to 19.5, p = 0.01). Clinicians prescribing SIR should maintain a high level of vigilance for VTE, particularly among patients with other risk factors for this complication.