TY - JOUR
T1 - Lessons From Ximelagatran
T2 - Issues for Future Studies Evaluating New Oral Direct Thrombin Inhibitors for Venous Thromboembolism Prophylaxis in Orthopedic Surgery
AU - Lazo-Langner, Alejandro
AU - Rodger, Marc A.
AU - Wells, Philip S.
PY - 2009/6
Y1 - 2009/6
N2 - Venous thromboembolism is a frequent complication of total hip and knee replacement requiring prophylaxis with anticoagulants. A direct thrombin inhibitor— ximelagatran—did not show advantages over other anticoagulants and it was withdrawn from the market; however, new drugs are being developed. We conducted a systematic review and meta-analysis to identify conditions under which ximelagatran might potentially be superior to current standards. Medline, EMBASE, the Cochrane Library, and grey literature were screened for randomized trials comparing ximelagatran with warfarin or low-molecular-weight heparin for thromboprophylaxis in total hip or knee replacement. Two reviewers independently assessed and extracted data. A meta-analysis with especial attention to statistical heterogeneity was conducted. This study suggested that the risk-benefit profile of ximelagatran—and probably other similar agents— depends on the type of surgery, the initial timing of administration, and probably the dose. These issues should be explicitly explored in future trials evaluating new direct thrombin inhibitors.
AB - Venous thromboembolism is a frequent complication of total hip and knee replacement requiring prophylaxis with anticoagulants. A direct thrombin inhibitor— ximelagatran—did not show advantages over other anticoagulants and it was withdrawn from the market; however, new drugs are being developed. We conducted a systematic review and meta-analysis to identify conditions under which ximelagatran might potentially be superior to current standards. Medline, EMBASE, the Cochrane Library, and grey literature were screened for randomized trials comparing ximelagatran with warfarin or low-molecular-weight heparin for thromboprophylaxis in total hip or knee replacement. Two reviewers independently assessed and extracted data. A meta-analysis with especial attention to statistical heterogeneity was conducted. This study suggested that the risk-benefit profile of ximelagatran—and probably other similar agents— depends on the type of surgery, the initial timing of administration, and probably the dose. These issues should be explicitly explored in future trials evaluating new direct thrombin inhibitors.
KW - direct thrombin inhibitors
KW - meta-analysis
KW - orthopedic surgery
KW - prophylaxis
KW - venous thromboembolism
KW - ximelagatran
UR - http://www.scopus.com/inward/record.url?scp=67649992641&partnerID=8YFLogxK
U2 - 10.1177/1076029608326166
DO - 10.1177/1076029608326166
M3 - Article
C2 - 19028773
AN - SCOPUS:67649992641
SN - 1076-0296
VL - 15
SP - 316
EP - 326
JO - Clinical and Applied Thrombosis/Hemostasis
JF - Clinical and Applied Thrombosis/Hemostasis
IS - 3
ER -