The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

Abstract

The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).

Atrial fibrillation and stroke: a practical guide

“…*Adapted from manufacturers’ SPCs and with reference to Steffel et al 95; consulting BNF and local guidelines also suggested.†Strong inhibitors of both CYP3A4 and P-gp: ketoconazole, itraconazole, voriconazole, posaconazole, dronedarone, HIV protease inhibitors (increased anticoagulant effect).‡Other inhibitors of CYP3A4 and P-gp (ie, with less potent inhibition of one or both pathways): clarithromycin, erythromycin, fluconazole (increased anticoagulant effect).§CYP3A4 inducers: rifampicin, phenytoin, carbamazepine, phenobarbitone, St. John’s wort (reduced anticoagulant effect).¶Strong P-gp inhibitors: as †, also ciclosporin, tacrolimus and erythromycin (increased anticoagulant effect).**Other P-gp inhibitors: verapamil (note dose reduction for dabigatran), amiodarone, quinidine, clarithromycin, ticagrelor (increased anticoagulant effect).††P-gp inducers: rifampicin, phenytoin, carbamazepine, phenobarbitone, St. John’s wort (reduced anticoagulant effect).Major warfarin interactions: allopurinol, azoles, omeprazole, amiodarone, tamoxifen, statins (especially fluvastatin), fibrates, erythromycin, metronidazole (increased effect); phenobarbitone, primidone, carbamazepine, rifampicin, phenytoin, azathioprine, St. John’s wort (reduced effect); steroids, nevirapine, ritonavir (unpredictable effects); liver, broccoli, sprouts, leafy greens (high vitamin K content—reduced effect).AF, atrial fibrillation; INR, international normalised ratio; N/A, not applicable.…”

“…*Adapted from manufacturers’ SPCs and with reference to Steffel et al 95; consulting BNF and local guidelines also suggested.…”

“…In the absence of an assay result excluding a significant effect of a DOAC, US guidelines advise against thrombolysis unless it can be clearly established that the patient last took the medication more than 48 hours ago and has normal renal function 27. The European Society of Cardiology recommends also considering thrombolysis for patients who last took a DOAC between 24 and 48 hours ago, if renal function is normal and they are otherwise a good candidate 95. In patients not meeting these criteria, proceeding directly to mechanical thrombectomy should be considered in patients with thrombus within the basilar artery or proximal middle cerebral artery.…”

“…For patients taking DOACs, there is no role for vitamin K supplementation, as DOACs act downstream of the vitamin K–dependent portion of the clotting cascade. Four-factor prothrombin complex concentrate has been used off-label, and is recommended by European Heart Rhythm Association guidelines,95 but there is only limited evidence for efficacy. For dabigatran, there is an available specific monoclonal antibody antidote, idarucizumab, which rapidly and safely normalised laboratory clotting indices and achieved normal intraoperative haemostasis in patients needing emergency surgery in an uncontrolled phase III study 102.…”

Oral anticoagulant use for stroke prevention in atrial fibrillation patients with difficult scenarios

“…On the basis of pharmacological modelling, rivaroxaban, apixaban and edoxaban (but not dabigatran) have been approved in Europe for thromboprophylaxis in patients with severe CKD (eGFR 15–29 mL/min) not on dialysis, using reduced-dose regimens [25]. Based on pharmacokinetic studies, the US Food and Drug Administration (FDA) also approved the use of reduced-dose dabigatran (75 mg bid) in patients with AF with an eGFR of 15–29 mL/min as well as the use of apixaban (5 mg bid) in patients with AF and end-stage renal disease (ESRD) on dialysis [26,27].…”