Highly effectve thromboembolism prophylaxis is underused because of concern about excessive bleeding risk and doubt about the clinical relevance of studies which reported asymptomatic venographic outcomes. One popular review concludes prophylaxis must be given close to surgery for optimum effectiveness. To address these issues, we tested the highly effective sq antithrombotic fondaparinux, a factor Xa inhibitor, initiated either 6-8 h after surgery (“early”) vs the next morning (“delayed”) in joint replacement patients.
Drug administration and observations were unblinded but adjudication of thromboembolism (VTE), bleeding, and cause of death were blinded. Outcomes were clinically symptomatic and objectively documented thromboembolism, major and clinically relevant non-major bleeding, and death due to complications of bleeding or thrombosis during the 6 weeks after surgery.
2000 patients, 1003 early and 997 delayed, were randomized and received at least one dose of assigned treatment. Among the early group, 19 had VTE (1.9%; 10 DVTs and 9 PEs). Among the delayed group, 18 had VTE (1.8%; 11 DVTs and 9 PEs, 2 patients with both). There were 4 deaths in the early group vs 1 in the delayed group (P=0.4), none related to VTE or bleeding. There were 12 major and 14 clinically relevant non-major bleeds in the early group, vs 7 and 19 respectively for the delayed group (P=0.4 for major bleeding). The early and late dosed groups appeared similar in other respects also.
In 2000 surgical patients, clinically evident thromboembolism risk over 6 weeks was no higher if initiation of highly effective prophylaxis was delayed until the morning after surgery. Clinically relevant bleeding rates were similar, but a trend suggested fewer major bleeds with initiation of fondaparinux delayed to the morning after surgery.
For this highly effective antithrombotic, delaying the first post-surgical dose until the morning after surgery did not appear to lessen clinical efficacy and may reduce major bleeding rates.
B. Davidson, Clinical research funds from Sanofi-Synthelabo