Does a longer duration of oral factor Xa therapy increase the risk of bleeding or transaminitis?

BACKGROUND: There is little data regarding the risk of bleeding or transaminitis with a longer duration of oral factor Xa therapy. Our goal was to analyze data from randomized trials to better define the relationship between drug duration and drug safety.

METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and several internet sources of data from 1988 through the second week of March 2010. We identified (1) randomized controlled trials that (2) compared oral factor Xa inhibitors to low molecular weight heparin (LMWH) or vitamin-K antagonists (3) in humans. There were no restrictions on journal type or population studied. The primary outcomes were any bleeding and transaminitis defined as an on treatment alanine aminotransferase increase greater than three times the upper limit of normal. All data was stratified into two groups: short duration (< 1 month of therapy) and long duration (> 1 month of therapy).

RESULTS: Seventeen randomized studies were identified which included a total of 24,979 patients for safety analysis. The relative risk of bleeding among patients treated with short duration therapy was 1.10 (95% CI=0.86-1.40; P=0.46) and long duration 0.99 (95% CI=0.82-1.20; P=0.94); there was no difference in the relative risk of bleeding between the duration groups (P=0.50). The relative risk of transaminitis among patients treated with short duration therapy was 0.75 (95% CI=0.55-1.04; P=0.08) and long duration 0.37 (95% CI=0.14-0.97; P=0.02); there was no difference in the relative risk of transaminitis between the duration groups (P=0.17).

CONCLUSIONS: In this analysis longer treatment duration does not increase either bleeding risk or the risk of liver injury.