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

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• 作者：Vivek N. Ahya MD^a ; ^{ahyav@uphs.upenn.edu} ; Pamela J. McShane MD^b ; Maher A. Baz MD^c ; Vincent G. Valentine MD^d ; Selim M. Arcasoy MD^e ; Robert B. Love MD^f ; Harish Seethamraju MD^g ; Edward Garrity MD^b ; Charles G. Alex MD^h ; Remzi Bag MDⁱ ; Nilto C. DeOliveira MD^j ; Wickii T. Vigneswaran MD^k ; Jeff Charbeneau MS^l ; Jerry A. Krishnan MD ; PhD^b ; Ramon Durazo-Arvizu PhD^m ; Lourdes Norwick BSN ; RN^b ; Sangeeta Bhorade MD^b
• 关键词：lung transplantation ; immunosuppression ; sirolimus ; venous thromboembolism ; mTOR (mammalian target of rapamycin) inhibitors
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：30
• 期：2
• 页码：175-181
• 全文大小：289 K

文摘

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.