Reversal of direct oral anticoagulants in adult hip fracture patients. A systematic review and meta-analysis.

BACKGROUND: Increasing numbers of patients are taking Direct Oral Anticoagulants at the time of hip fracture. Evidence is limited on how and if the effects of DOAC's should be reversed before surgical fixation. Wide variations in practice exist. We conducted a systematic review to investigate outcomes for three reversal strategies. These were: "watch and wait" (also referred to as "time-reversal"), plasma product reversal and reversal with specific antidotes.

METHODS: A systematic search was conducted using multiple databases. Results were obtained for studies directly comparing different DOAC reversal strategies in hip fracture patients and for studies comparing DOAC-taking hip fracture patients (including patients "reversed" using any method and "non-reversed" patients) against matched controls taking either a vitamin-K antagonist or not receiving anticoagulation therapy. This allowed construction of a network meta-analysis to indirectly compare outcomes between "reversed" and "non-reversed" DOAC patients. With respect to "watch and wait"/"time-reversal", a cut-off time to surgery of 36 hours was used to distinguish between "time-reversed" and "non time-reversed" DOAC patients. The primary outcome was early/inpatient mortality, reported as Odds Ratios (OR).

RESULTS: No studies investigating plasma products or reversal agents specifically in hip fracture patients were obtained. Fourteen studies were suitable for analysis of "watch and wait"/"time- reversal". Two studies directly compared "time-reversed" and "non time-reversed" DOAC-taking hip fracture patients (58 "time-reversed", 62 "non time-reversed"). From 12 other studies we used indirect comparisons between "time-reversed" and "non time-reversed" DOAC patients (total, 357 "time-reversed", 282 "non time-reversed"). We found no statistically significant differences in mortality outcomes between "time-reversal" and "non time-reversal" (OR 1.48 [95%CI: 0.29-7.53]). We also did not find a statistically significant difference between "time reversal" and "non time-reversal" in terms of blood transfusion requirements (OR 1.16 [95% CI 0.42-3.23]). However, several authors described that surgical delay is associated with worse outcomes related to prolonged hospitalisation, and that operating within 36 hours is safe.

CONCLUSIONS: We suggested against "watch and wait" to reverse the DOAC effect in hip fractures. Further work is required to assess the optimal timing for surgery as well as the use of plasma products or specific antidotes in DOAC-taking hip fracture patients.