In this episode, I’ll discuss whether DOACs ever require bridging.
When the only oral anticoagulant available was warfarin, patients who experienced a thromboembolic event required a bridging period with unfractionated or low molecular weight heparin when starting warfarin therapy. The reasons for this bridging are two-fold:
1. In the initial period of starting warfarin a paradoxically increased state of coagulation exists and without bridging the patient is at risk of worsening of the clot.
2. Due to warfarin’s mechanism of action and the long half-life of some coagulation factors, the effects of warfarin to provide a therapeutic level of anticoagulation do not occur immediately.
Because direct oral anticoagulants such as dabigatran, apixaban, rivaroxaban, and edoxaban provide their effects immediately they do not require bridging with unfractionated or low molecular weight heparin when starting therapy.
While some trials for these DOACs included a few days of unfractionated or low molecular weight heparin before transitioning to the DOAC, no study has ever used an overlapping administration period or bridge with a DOAC and unfractionated or low molecular weight heparin.
Despite this information, I have occasionally had providers request to bridge patients with new VTE using unfractionated or low molecular weight heparin at the same time as a DOAC. I know of colleagues who have had the same request made of them. The scenario usually looks something like this:
The patient has a pulmonary embolism or bilateral deep venous thrombosis and the risk of clot propagation is perceived to be high by the clinician. So they order a DOAC plus unfractionated or low molecular weight heparin to bridge the patient for a day or two. Sometimes the provider is amenable to education about the nature of DOACs and the lack of the need for bridging, but sometimes they are insistent on providing the bridge therapy.
While this has never been subjected to a study, all of the available pharmacokinetic data refutes the need to bridge DOACs.
The CMax for dabigatran, apixaban, rivaroxaban, and edoxaban after oral administration is 1, 3, 3, and 2 hours respectively.
The CMax for subcutaneous enoxaparin occurs within 3 to 5 hours, so the bridge with enoxaparin would actually take effect *after* the DOAC did, not before.
While the CMax for IV heparin would be immediate, heparin protocols do not provide immediate therapeutic anticoagulation to most patients. A study that evaluated an unfractionated heparin pharmacy dosing protocol for the treatment of VTE found that the average time to the first therapeutic lab value was 15 hours. This is also well beyond the time where a DOAC would reach a therapeutic level.
While the simultaneous use of unfractionated or low molecular weight heparin with a DOAC at therapeutic levels has never been studied, there is reason to believe the effects of combining these medications would be additive and expose a patient to double the therapeutic level of anticoagulation. A randomized crossover trial gave patients apixaban 5 mg and enoxaparin 40 mg concomitantly. In this arm of the study, peak anti-Xa activity was 42% higher than for apixaban alone.
While I usually practice by the guideline, “never say never,” I cannot think of any situation where it would ever be appropriate to bridge a patient starting a DOAC with unfractionated or low molecular weight heparin. Based on available data bridging DOACs appears to unnecessarily put a patient at risk of excessive anticoagulation levels without any evidence or expectation of benefit to compensate for this risk.
Members of my Hospital Pharmacy Academy have access to practical training on transitioning between anticoagulants, DOAC interactions, monitoring heparin with Anti-Xa levels, and many more resources to help in your practice. To get immediate access, go to pharmacyjoe.com/academy.
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Great one Pharmacy Joe!
Thank you Jen!