The effectiveness and safety of direct oral anticoagulants compared to conventional pharmacologic thromboprophylaxis in hip fracture patients: A systematic review and meta-analysis of randomized controlled trials

Abstract

BackgroundDirect oral anticoagulants (DOACs) are recommended as a possible pharmacologic venous thromboembolism (VTE) prophylaxis in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, current guidelines did not introduce recommendations for administration of DOACs as an option for pharmacologic VTE prophylaxis in patients undergoing hip fracture surgery (HFS). The purpose of this study is to compare the effectiveness and safety of DOACs administered for pharmacologic VTE prophylaxis in patients undergoing HFS to conventional pharmacologic VTE prophylaxis, as well as mortality between these thromboprophylaxis medications. MethodsWe performed a systematic review of multiple electronic databases for randomized controlled trials (RCTs) including patients who were subjected to HFS and prescribed either DOACs as pharmacologic VTE prophylaxis or a conventional VTE prophylaxis drug. We conducted a meta-analysis comparing effectiveness, safety and mortality of these agents between the patient groups studied. Three endpoints were studied. The first one regarding the effectiveness of the agents included clinical manifestations of VTE. The second one regarding the safety of the agents included clinical presentation of bleeding. The latter endpoint studied was mortality of patient groups studied. We generated forest plots to depict the relative risk of the above clinical manifestations between the two studied patient groups and to investigate if there is statistical significance for each patient group to present any of these clinical manifestations. Additionally, we calculated the inconsistency (I2) statistic and assessed the risk of bias of RCTs included in our meta-analysis by using the modified Cochrane collaboration tool. ResultsWe selected 2 RCTs in this review including 279 patients totally. Patients of control groups in both eligible studies were administered enoxaparin, which is a low molecular weight heparin (LMWH). The meta-analysis found no statistically significant difference between patients prescribed DOACs and patients prescribed LMWH for VTE (95% CI 0.19 to 1.13, RR=0.46, p=0.09), deep vein thrombosis (DVT) (95% CI 0.21 to 1.32, RR=0.53, p=0.17) and pulmonary embolism (PE) (95% CI 0.03 to 3.12, RR=0.33, p=0.33), major bleeding events (95% CI 0.57 to 1.78, RR=1.01, p=0.97), minor bleeding events (95% CI 0.72 to 1.64, RR=1.09, p=0.69), all bleeding events (95% CI 0.79 to 1.38, RR=1.05, p=0.74) and mortality (95% CI 0.01 to 8.0, RR=0.33, p=0.5). The major risk of bias of the selected RCTs was the fact that either the researchers or the patients could have knowledge whether the latter were administered DOACs or LMWHs. DiscussionDOACs are not inferior compared to LMWHs regarding their effectiveness, safety and mortality in patients subjected to HFS. Further studies with larger patient samples should be conducted in the future, so that safer results and conclusions could be reached.