TY - JOUR
T1 - Increased risk of venous thromboembolism with a sirolimus-based immunosuppression regimen in lung transplantation
AU - Ahya, Vivek N.
AU - McShane, Pamela J.
AU - Baz, Maher A.
AU - Valentine, Vincent G.
AU - Arcasoy, Selim M.
AU - Love, Robert B.
AU - Seethamraju, Harish
AU - Garrity, Edward
AU - Alex, Charles G.
AU - Bag, Remzi
AU - Deoliveira, Nilto C.
AU - Vigneswaran, Wickii T.
AU - Charbeneau, Jeff
AU - Krishnan, Jerry A.
AU - Durazo-Arvizu, Ramon
AU - Norwick, Lourdes
AU - Bhorade, Sangeeta
N1 - Funding Information:
Financial support was provided by Astellas, Pharma, Inc . None of the authors has personal or financial conflicts of interest related to the topics discussed in this manuscript. This study, however, was an investigator-initiated industry sponsored study.
PY - 2011/2
Y1 - 2011/2
N2 - Background 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. Methods 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. Results 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). Conclusion Clinicians prescribing SIR should maintain a high level of vigilance for VTE, particularly among patients with other risk factors for this complication.
AB - Background 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. Methods 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. Results 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). Conclusion Clinicians prescribing SIR should maintain a high level of vigilance for VTE, particularly among patients with other risk factors for this complication.
KW - drug toxicity
KW - immunosuppression
KW - lung transplantation
KW - mTOR (mammalian target of rapamycin) inhibitors
KW - sirolimus
KW - venous thromboembolism
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U2 - 10.1016/j.healun.2010.08.010
DO - 10.1016/j.healun.2010.08.010
M3 - Article
C2 - 20947384
AN - SCOPUS:78650961986
SN - 1053-2498
VL - 30
SP - 175
EP - 181
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 2
ER -