Activity Transcript

Susan J. Mayor, PhD: Hello and welcome to the third and final episode of this season's Thrombosis TV -- Addressing Common Challenges in Anticoagulation in Atrial Fibrillation: When a Patient Needs a Procedure. I'm Susan Mayor.

The predominant challenge in managing anticoagulant therapy in patients with atrial fibrillation (AF) is balancing the risk of stroke with the risk of bleeding. In episode 1, we discussed how underusing and underdosing non-vitamin-K oral anticoagulants, the NOACs, to reduce bleeding risk in patients with AF significantly increases the risk of stroke. In this episode, we look at another challenge in balancing stroke risk and bleeding risk in patients with AF -- how to adjust NOAC dosing before, during, and after a surgical or medical intervention.

Our focus is on elective interventions that are associated with relatively low risk of problematic bleeding events rather than emergency or major surgical interventions associated with very high risk of serious bleeding, where the use of specific NOAC reversal agents may be considered.

To get the latest guidance and perspectives for addressing this challenge, I met with Dr Tatjana Potpara, head of the Department of Intensive Care in Cardiac Arrhythmias at the Cardiology Clinic at the Clinical Center of Serbia in Belgrade and Assistant Professor of Internal Medicine and Cardiology at the School of Medicine at Belgrade University.

Good morning, Tatjana. Thank you for participating in our program today.

Tatjana Potpara, MD, PhD: My pleasure, Susan.

Dr Mayor: Overall, what is your approach to maintaining safe and effective NOAC therapy in patients with atrial fibrillation undergoing an elective surgical or medical intervention that may cause a problematic bleeding event?

Dr Potpara: Well, first, we need to distinguish between challenges that are real and those that are more related to patient and physician perceptions. There are numerous elective surgical and medical interventions ranging from, for example, removal of a skin lesion to tooth extractions to percutaneous coronary intervention (PCI) to hip replacement surgery. The decision whether to discontinue or adjust the dosage of a NOAC before, during, and/or after these interventions depends on the level of invasiveness and bleeding risk. Assessment of bleeding risk is based on the potential clinical impact associated with the intervention.

In addition, certain patient characteristics, such as age, kidney function, history of bleeding issues, comorbidities, and concomitant medications, also factor into the decision. In general, guidelines recommend against discontinuing NOACs for most minor- and low-bleeding-risk interventions. However, dosage adjustments may be appropriate, depending on the level of bleeding risk, time of surgery, and prescribed dosing schedule of the NOAC. In contrast, high-bleeding-risk interventions, such as major surgery, often require discontinuation of NOAC therapy for 1 or 2 days before the procedure through 1 or 2 days after the procedure.

Dr Mayor: You mentioned elective interventions that are associated with a minor and low bleeding risk. Can you provide examples of these types of interventions and the recommended guidelines for adjustments in NOAC therapy?

Dr Potpara: A widely used practical guide for the management of NOAC therapy in patients with AF, including those undergoing an elective intervention, is published by the European Heart and Rhythm Association (EHRA).^[1] The EHRA document classify elective interventions into 3 categories of bleeding risk – minor, low, and high -- based on the frequency of bleeding and its potential clinical impact on the patient. Common examples of interventions portending a minor risk of bleeding include most dental procedures, cataract and glaucoma surgeries, endoscopy without biopsy or resection, and superficial skin excisions. Common examples of interventions classified as having a low risk of bleeding include endoscopy with biopsy, uncomplicated catheter ablation, and non-coronary angiography. Uncomplicated pacemaker and defibrillator implantations would also be classified as having a low bleeding risk. As a rule of thumb, elective minor- and low-bleeding risk interventions can be performed 12 to 24 hours after the last NOAC dose. On the other side of the equation, NOACs can be administered 6 hours after the intervention, as long as the patient has achieved adequate hemostasis.

Dr Mayor: Let's say a patient on NOAC therapy for AF is undergoing an elective intervention associated with a minor risk of bleeding. What determines whether a dosing adjustment is necessary?

Dr Potpara: For elective minor-bleeding-risk interventions, no changes in NOAC dosing are necessary the day before and the day after the procedure. On the day of the intervention, however, dosing adjustments would depend on the time of day, whether the NOAC is dosed once or twice daily, and, if dosed once daily, whether the patient is routinely taking the daily dose in the morning or evening.

Dr Mayor: Can you be more specific about the recommended dosing adjustments for each of the 4 NOACs for a minor-bleeding-risk intervention? Let's say the intervention is scheduled for the morning.

Dr Potpara: Well, for dabigatran or apixaban, which are dosed twice daily, the patient would take only 1 dose on the day of the intervention, at least 6 hours after the procedure. For rivaroxaban and edoxaban, which are dosed once daily, the daily dose would be administered regularly in the evening or at least 6 hours after the morning intervention in patients regularly taking their NOAC in the morning.

Dr Mayor: Ok, what about interventions associated with the next category of bleeding risk – a low risk of bleeding? What are the dosing adjustment recommendations for the 4 NOACs for these types of interventions? Once again, let's assume the intervention takes place in the morning.

Dr Potpara: The major difference between minor- and low bleeding risk interventions is that the latter may require a NOAC dosing adjustment the day before the procedure. For twice-daily dabigatran and apixaban, the patient would skip the evening dose the day before the intervention, skip the morning dose the day of the intervention, and restart the evening dose at least 6 hours after the intervention. For once-daily rivaroxaban and edoxaban, the dosing adjustment again depends on when the patient routinely takes their daily dose. Patients who take their daily dose in the morning would take it in the morning the day before a morning intervention but postpone the next dose until at least 6 hours after the intervention. Patients who take their daily dose in the evening (which is the recommended timing for rivaroxaban) would skip the evening dose the day before a morning intervention and resume the evening dose at least 6 hours after the intervention.

Dr Mayor: Would impaired renal function associated with chronic kidney disease impact the recommended dosing adjustments for interventions associated with a minor or low risk of bleeding?

Dr Potpara: It depends on the NOAC. For dabigatran, which is 80% excreted by the kidneys, graded increases in the amount of time between the last dose and the start of most elective low-bleeding-risk interventions are recommended for patients with a creatinine clearance under 80 mL/min. For the other NOACs, the dosing guidance is the same for patients with a creatinine clearance greater than 30 mL/min, but the amount of time between last dose and the intervention is increased for patients with a creatinine clearance (CrCl) below 30 mL/min.

Dr Mayor: What happens if a patient undergoing a minor- or low-bleeding-risk elective intervention experiences a problematic bleeding event? How would that affect the resumption of NOAC therapy after the intervention?

Dr Potpara: Local hemostatic measures are usually sufficient to resolve most bleeding issues resulting from minor- and low-bleeding-risk interventions. However, the patient should not leave the clinic or hospital or resume oral anticoagulation until all peri-interventional bleeding has been completely stopped.

Dr Mayor: One of the low-bleeding-risk interventions mentioned by Dr Potpara is percutaneous coronary intervention, PCI. Many patients with AF also have or may develop coronary artery disease and will require PCI at some point while on anticoagulant therapy. Although the intervention itself is associated with a low bleeding risk, PCI presents a challenge because it requires extended post-procedural antiplatelet therapy to prevent a recurrent coronary ischemic event and stent thrombosis. And we know that concomitant anticoagulant and antiplatelet therapy significantly increases bleeding risk. I asked Dr Potpara what her approach would be to managing NOAC therapy in patients with AF who undergo elective PCI for chronic coronary artery disease rather than for an acute event.

Dr Potpara: Patients with AF who require PCI for symptomatic chronic coronary artery disease (CAD) present a complex clinical scenario on several fronts. One is that they tend to be older and have underlying comorbidities such as hypertension, hyperlipidemia, and diabetes. So, these patients are at an increased risk for stroke due to their AF, an increased risk of a coronary ischemic event due to their CAD, and an increased risk of anticoagulant- and antiplatelet therapy-related bleeding due to their age and underlying comorbidities.

Although there is a range of options in terms of the intensity and duration of antiplatelet therapy after PCI, an absolute in patients with AF is the need to maintain anticoagulant therapy at the recommended dosage to prevent stroke, as either P2Y₁₂ inhibitors or aspirin, or their combinations would not provide optimal protection from AF-related stroke, which is why AF patients must continue their anticoagulant therapy. On the other hand, NOACs are not sufficient in themselves to protect against coronary ischemic events and stent thrombosis, which is why antiplatelet therapy is recommended after PCI. The decision involves whether to administer a P2Y₁₂ inhibitor or aspirin or both, and for how long.

Dr Mayor: What is the clinical evidence up to this point on the efficacy and safety of NOACs in combination with antiplatelet therapy after PCI in patients with AF and chronic CAD?

Dr Potpara: Several randomized controlled trials (RCTs) have compared dual and triple therapy including an oral anticoagulant (OAC) (be it a vitamin-K antagonist [VKA] or a NOAC) in combination with a P2Y₁₂ inhibitor (so-called dual therapy), or a P2Y₁₂ inhibitor and aspirin (triple therapy) in the management of AF patients with either an acute coronary syndrome (ACS) or chronic CAD undergoing a PCI.^[2] Although some uncertainties remain, a few conclusions have been reached. One is that dual therapy with a NOAC and P2Y₁₂ inhibitor, specifically clopidogrel, is associated with a significantly lower risk of major and fatal bleeding events compared with triple therapy with warfarin, clopidogrel, and aspirin. There was no significant difference in the risk of myocardial infarction (MI), stent thrombosis, stroke and mortality between dual and triple therapy in either of the 4 RCTs, but these trials were not powered for the assessment of ischemic events, and several meta-analyses of the RCTs reported conflicting findings ranging from no difference in ischemic events with dual vs triple therapy to increased risk of MI or stent thrombosis with dual therapy, but increased risk of intracerebral hemorrhage (ICH) with triple therapy (especially with warfarin). In addition, NOACs were shown to be safer than VKAs in any combination. Hence, the area of controversy centers on whether there is a net clinical benefit of adding aspirin to dual therapy – so-called triple therapy -- and, if so, for how long after a PCI.

Dr Mayor: What does the latest clinical trial evidence suggest?

Dr Potpara: Overall, the decision of whether to prescribe a course of triple therapy after PCI (and for how long – for example, until discharge or for a week) needs to be individualized based on the patient's relative risks of a critical ischemic event and major bleeding event. Of note, patients in all pertinent RCTs were taking triple therapy at least on the day of PCI or until randomization to dual or triple therapy.

Dr Mayor: You mentioned clinical trials supporting the use of clopidogrel in combination with NOACs in the treatment of patients with atrial fibrillation undergoing PCI. Is there any evidence supporting the efficacy and safety of other P2Y₁₂ inhibitors in combination with NOACs?

Dr Potpara: To this point, clinical trials evaluating combination anticoagulant and antiplatelet therapy in AF patients after PCI have not included a sufficient number of patients using ticagrelor and prasugrel to draw any conclusions about their relative safety and efficacy. But one would expect that there may be more bleeding with a more potent antiplatelet agent.

Dr Mayor: Earlier in our conversation, you mentioned the importance of distinguishing between interventions that involve a real risk of serious bleeding and those that are more related to patient and physician perceptions. Do you find that patient and physician perceptions have an impact on the management of atrial fibrillation during elective interventions?

Dr Potpara: Yes, they do. Those of us who regularly see patients with AF clearly understand the net clinical benefit provided by OAC despite the associated risk of bleeding. However, although stroke is one of the most catastrophic medical events that can befall a patient, OAC benefit a patient by reducing the risk of an event that has not yet happened and may never happen. In the meantime, anticoagulant-related bleeding, even if relatively minor and manageable, happens in the present, may be very upsetting for many patients, and is related to a drug they are taking. So, there can be a tendency for patients to underdose or discontinue their NOAC in anticipation of a procedure to avoid unpleasant bleeding, especially if they have experienced a bleeding event in the past. For this reason, it's important for clinicians to understand their patients' perceptions of their condition and their self-perceived treatment burdens so they can more effectively communicate with their patients and ensure their adherence to dosing guidelines. Although NOACs have significantly reduced patient-perceived bleeding risks compared with VKAs, concern about both minor and major bleeding events can still be a barrier to adherence for many patients.

Dr Mayor: Tatjana, we're almost out of time. Do you have any key take-home messages for our audience pertaining to our discussion?

Dr Potpara: In navigating the balance between stroke prevention, and bleeding risk in patients with AF undergoing an elective intervention, it's essential to realistically evaluate the potential positive and negative consequences of NOAC dosing adjustments. Decisions on peri-interventional NOAC dosing adjustments should be based on the bleeding risk associated with the intervention, specific NOAC label, and an individualized assessment of a patient's relative risks for stroke and bleeding. If the patient is undergoing PCI, the risk of a coronary ischemic event and the consequences of intensity and duration of antiplatelet therapy also need to factor into the decision.

Dr Mayor: This concludes the final episode of this season's Thrombosis TV. We hope you found this episode, as well as the entire series, to be informative and relevant to your practice. To proceed to the online CME test, click on the earn CME credit link on this page.

And thank you for watching this program.

This is a verbatim transcript and has not been copyedited