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.
Division of Pulmonary, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. ahyav@uphs.upenn.edu
Vivek N
VN
Ahya
Pamela J
PJ
McShane
Maher A
MA
Baz
Vincent G
VG
Valentine
Selim M
SM
Arcasoy
Robert B
RB
Love
Harish
H
Seethamraju
Edward
E
Garrity
Charles G
CG
Alex
Remzi
R
Bag
Nilto C
NC
DeOliveira
Wickii T
WT
Vigneswaran
Jeff
J
Charbeneau
Jerry A
JA
Krishnan
Ramon
R
Durazo-Arvizu
Lourdes
L
Norwick
Sangeeta
S
Bhorade
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