The role of aspirin in the prevention of thrombotic complications of thalidomide and anthracycline-based chemotherapy for multiple myeloma.
OBJECTIVE
To study the efficacy of daily low-dose aspirin (81 mg orally) in decreasing the incidence of venous thromboembolic events (VTEs) in patients with multiple myeloma receiving pegylated doxorubicin, vincristine, and decreased-frequency dexamethasone, plus thalidomide (DVd-T).


METHODS
In this phase 2 clinical trial of DVd-T, conducted by the Cleveland Clinic Foundation from August 2001 to October 2003, 105 patients were enrolled. The first 35 patients experienced increased numbers of VTEs. von Willebrand levels and platelet aggregation to ristocetin before and after treatment with DVd-T increased significantly, suggesting a pathophysiology involving platelet-endothelial interaction. Aspirin was added to the regimen, thus generating 3 patient groups: group 1 received aspirin from the start of DVd-T treatment before the study began (58 patients), group 2 received aspirin after the start of DVd-T treatment and after the study began (26 patients), and group 3 did not receive daily low-dose aspirin during the study (19 patients). Two patients being treated with warfarin for other indications were excluded from the study. The primary end point for this study was the incidence of VTE in the form of either deep venous thrombosis or pulmonary embolism. Secondary end points were the time to the first VTE, time to the composite end point of death or first VTE, and incidence of bleeding complications.


RESULTS
After a median follow-up of 24 months, on an intent-to-treat basis, 26 posttreatment VTEs occurred after a median of 90 days, with 19% occurring in group 1, 15% in group 2, and 58% in group 3. Following multivariate time-to-event analysis, aspirin use continued to be associated with lower relative risk of VTE (hazard ratio, 0.22; confidence interval, 0.10-0.47; P<.001) and of the composite end point (hazard ratio, 0.28; confidence interval, 0.15-0.51; P<.001).


CONCLUSIONS
Daily low-dose aspirin (81 mg orally) given to patients with newly diagnosed and relapsed/refractory multiple myeloma who were receiving DVd-T reduced the incidence of VTEs without an increase in bleeding complications.
Baz
Rachid
R
Cleveland Clinic Myeloma Research Program, Cleveland Clinic Foundation, OH 44195, USA.
Li
Liang
L
Kottke-Marchant
Kandice
K
Srkalovic
Gordan
G
McGowan
Bridget
B
Yiannaki
Erin
E
Karam
Mary Ann
MA
Faiman
Beth
B
Jawde
Rony Abou
RA
Andresen
Steven
S
Zeldis
Jerome
J
Hussein
Mohamad A
MA
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects*; D020246:Venous Thrombosis / Q000139:chemically induced* / Q000517:prevention & control*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D005343:Fibrinolytic Agents; D007166:Immunosuppressive Agents; D013792:Thalidomide; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D001241:Aspirin