Predictive Factors and Clinical Events Associated with Edoxaban Interruption and Heparin Bridging Strategy: EMIT-AF/VTE

Abstract

Patients treated with edoxaban may require diagnostic and therapeutic procedures that involve edoxaban interruption. Although heparin bridging strategies are not recommended, heparin is frequently used in clinical practice. However, whether heparin use decreases thromboembolic risk remains unclear, and the potential for increased periprocedural bleeding remains a concern. Here, we report factors predicting edoxaban interruption and the use of heparin bridging strategies and associated clinical events from Global EMIT-AF/VTE, a multicenter, prospective, noninterventional study (Clinicaltrials.gov NCT02950168). Eligible patients are adults with atrial fibrillation or venous thromboembolism treated with edoxaban who underwent a diagnostic or therapeutic procedure. Edoxaban interruption, heparin bridging strategies, and clinical event data were collected from 5 days before procedure through 29 days afterwards. Edoxaban was interrupted in 1222/2089 procedures (58.5%); a heparin bridging strategy was used during 178 (14.6%) of these interruptions. Patients who received periprocedural heparin had higher baseline HAS-BLED (2.4±1.0 vs 1.9±1.1, P <0.0001) scores and similar CHA₂DS₂-VASc (3.6±1.6 vs 3.4±1.6, P = 0.09) scores versus patients who did not. HAS-BLED score >3 and high EHRA procedural risk predicted both edoxaban interruption and the use of a heparin bridging strategy, whereas CHA₂DS₂-VASc scores did not predict either. Bleeding and ischemic event rates were low; the all-bleeding rate was higher with the use of a heparin bridging strategy versus without (6.2% vs 3.1%, P = 0.04). Periprocedural heparin use was associated with higher bleeding rates, but not with lower thromboembolic risk. Individual patient and procedural bleeding risks appear to contribute more than stroke risk to clinicians' consideration of a heparin bridging strategy.

Keywords: atrial fibrillation; bleeding; edoxaban; heparin bridging strategy; treatment interruption.

Figure 1.

Predictors of edoxaban interruption (A) and the use of a heparin bridging strategy. (B) EHRA risk category denotes procedural bleeding risk. CI, confidence interval; EHRA, European Heart Rhythm Association; HAS-BLED, hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly.

Figure 2.

Duration of edoxaban interruption by EHRA risk and the use of a heparin bridging strategy. ^aDuration could not be calculated for one patient. *P <0.0001, with a heparin bridging strategy versus without a heparin bridging strategy. EHRA, European Heart Rhythm Association.

Figure 3.

Clinical events with and without edoxaban interruption (A) or the use of a heparin bridging strategy (B). *P = 0.0371, with a heparin bridging strategy versus without a heparin bridging strategy; statistical analyses were only performed on all bleeding due to low event numbers. CRNMB, clinically relevant non-major bleeding; CV, cardiovascular; MB, major bleeding.