We read with interest the meta-analysis by Komócsi et al, which reported that the use of factor Xa and direct thrombin inhibitors in patients receiving antiplatelet therapy after an acute coronary syndrome (ACS) was associated with a substantial increase in major bleeding and moderate reduction in ischemic events.1 However, there are a few issues we would like to highlight.
Although a lack of publication bias was reported, a highly relevant source for retrieving randomized clinical trials (RCTs), the Cochrane Central Register of Controlled Trials (CENTRAL), should have been searched for completeness. Furthermore, an eligible study that is missing is a phase 2, 3-stage RCT by Goldstein et al,2 which randomized 2753 patients with ACS to either placebo or letaxaban, a factor Xa inhibitor (doses from 10 mg twice daily to 120 mg twice daily). A significant dose-dependent increase in major bleeding and a clinically significant increase in nonmajor bleeding were observed with letaxaban compared with placebo. Although the full publication of this trial is pending, it should be referred to in the article by Komócsi et al1 as a study awaiting classification.