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


CONCLUSIONS
Clinicians prescribing SIR should maintain a high level of vigilance for VTE, particularly among patients with other risk factors for this complication.
Ahya
Vivek N
VN
Division of Pulmonary, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. ahyav@uphs.upenn.edu
McShane
Pamela J
PJ
Baz
Maher A
MA
Valentine
Vincent G
VG
Arcasoy
Selim M
SM
Love
Robert B
RB
Seethamraju
Harish
H
Garrity
Edward
E
Alex
Charles G
CG
Bag
Remzi
R
DeOliveira
Nilto C
NC
Vigneswaran
Wickii T
WT
Charbeneau
Jeff
J
Krishnan
Jerry A
JA
Durazo-Arvizu
Ramon
R
Norwick
Lourdes
L
Bhorade
Sangeeta
S
D001379:Azathioprine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects* / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D054556:Venous Thromboembolism / Q000453:epidemiology*
D007166:Immunosuppressive Agents; D001379:Azathioprine; D011241:Prednisone; D020123:Sirolimus; D016559:Tacrolimus