Summary

• For adult and pediatric patients currently receiving an anticoagulant other than warfarin, start XARELTO 0 to 2 hours prior to the next scheduled evening administration of the drug and omit administration of the other anticoagulant. For unfractionated heparin (UFH) being administered by continuous infusion, stop the infusion and start XARELTO at the same time.¹
• For adult and pediatric patients currently taking XARELTO and transitioning to an anticoagulant with rapid onset, discontinue XARELTO and give the first dose of the other anticoagulant (oral or parenteral) at the time that the next XARELTO dose would have been taken.¹
• A subgroup analysis of the EINSTEIN program evaluated the effect of prestudy heparin on the safety and efficacy of XARELTO compared to enoxaparin and vitamin K antagonists (VKAs). There were no significant differences found in the incidences of recurrent venous thromboembolism (VTE) or major and nonmajor clinically relevant bleeding amongst the treatment groups, regardless of prestudy heparin use.²
• Additional citations identified during a literature search have been included in the REFERENCES section for your review.^3-9

CLINICAL STUDIES

EINSTEIN: Treatment of Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), and Reduction in the Risk of Recurrence of DVT and of PE

The EINSTEIN-DVT study was a phase 3, randomized, open-label, event-driven, noninferiority study that compared oral XARELTO alone (15 mg twice daily [BID] for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin (1.0 mg/kg BID) followed by dose-adjusted VKA (warfarin or acenocoumarol) in patients with confirmed symptomatic DVT without symptomatic PE.¹⁰ The EINSTEIN-PE study was a phase 3, randomized, open-label, event-driven, noninferiority study that evaluated the efficacy and safety of oral XARELTO (15 mg BID for 3 weeks followed by 20 mg once daily) vs subcutaneous enoxaparin (1.0 mg/kg BID) followed by dose-adjusted oral VKA in patients with acute symptomatic PE with or without DVT.¹¹

Prandoni et al (2015)² performed a retrospective, posthoc, subgroup analysis of patients in the EINSTEIN program. This analysis evaluated the effect of prestudy heparin on the safety and efficacy of XARELTO compared with enoxaparin in combination with and followed by VKA. Study medication was initiated immediately after randomization, but for XARELTO patients who received parenteral anticoagulation before randomization, the initial dose of XARELTO was given 4, 12, and 24 hours after the discontinuation of intravenous UFH, low-molecular-weight heparin (LMWH; with a twice-daily regimen), and fondaparinux or LMWH with a once-daily regimen, respectively.

• Primary efficacy outcome: acute, symptomatic VTE, which was defined as a composite of DVT and nonfatal or fatal PE.
• Principal safety outcome: clinically relevant bleeding, which was a composite of major and nonmajor clinically relevant bleeding.
• A total of 6937 (83.8%) of the 8281 randomized patients received prestudy heparin and 1344 (16.2%) patients did not.
  • The median duration of prestudy heparin treatment was 1.04 ± 0.74 days and 1.03 ± 0.42 days in the XARELTO and standard treatment groups, respectively.
• The patient demographics were similar between treatment groups, with the exception of mean body mass index, which was significantly lower in patients who did not receive prestudy heparin.
• The 3-month incidences of recurrent VTE were similar among the XARELTO and enoxaparin/VKA groups who did not receive prestudy heparin and who did receive prestudy heparin. Table: Incidence of Recurrent VTE Up to 3 Months in Relation to Duration of Prestudy Heparin Use provides the incidence of recurrent VTE up to 3 months in relation to duration of prestudy heparin use.
  • The incidence of recurrent VTE was not related to the duration of prestudy heparin treatment (P_trend=0.77).

• The 14-day incidences of major or nonmajor clinically relevant bleeding were similar among the XARELTO and enoxaparin/VKA groups in patients who did not receive prestudy heparin and those who did receive prestudy heparin. Table: Incidence of Bleeding Outcomes Up to 14 Days in Relation to Prestudy Heparin Use provides the incidence of bleeding outcomes up to 14 days in relation to prestudy heparin use.
• Incidences of major bleeding were found to be numerically lower, but not significantly lower, in the XARELTO group, regardless of prestudy heparin use.

Dingus et al (2022)¹² conducted a retrospective cohort analysis to compare the safety and efficacy of monitoring UFH infusions using an activated partial thromboplastin time (aPTT) titration scale versus utilizing an UFH-calibrated anti-Xa titration scale aided by treatment guidelines in patients transitioning from a Factor Xa inhibitor (FXai) to an UFH infusion.

The study reviewed patients’ electronic medical records from June 1, 2018, to November 1, 2020. Patients included were 18 years of age or older with XARELTO or apixaban on their home medication list and had a documented dose of XARELTO or apixaban within 72 hours of receipt of an order to initiate a therapeutic UFH infusion. Patients that were included were placed into the aPTT group or UFH anti-Xa group.¹²

Baseline characteristics identified more patients receiving apixaban than XARELTO in the anti-Xa guideline group (76.9% vs 23.1, respectively) versus the aPTT group (55.9% vs 44.1, respectively).¹²

The primary endpoint was a composite of death, major bleeding, or new thrombosis. All events had to occur after UFH initiation to be counted.¹²

After screening 623 patients, 279 patients were included in the study (anti-Xa guideline group: n=143; aPTT group: n=136). The primary composite endpoint met noninferiority criteria (6.3% vs 11% for anti-Xa vs aPTT, absolute risk reduction of 4.7%, 95% CI: -1.9% to 11.3%, P<0.001 for noninferiority) but was not found to be superior (P=0.159).¹²

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 25 September 2024.