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. 2021 Oct 9;23(10):1612-1676.
doi: 10.1093/europace/euab065.

2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation

Jan Steffel  1 , Ronan Collins  2 , Matthias Antz  3 , Pieter Cornu  4 , Lien Desteghe  5   6 , Karl Georg Haeusler  7 , Jonas Oldgren  8 , Holger Reinecke  9 , Vanessa Roldan-Schilling  10 , Nigel Rowell  11 , Peter Sinnaeve  12 , Thomas Vanassche  12 , Tatjana Potpara  13 , A John Camm  14 , Hein Heidbüchel  5   6 ; External reviewers
Collaborators, Affiliations

2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation

Jan Steffel et al. Europace. .

Erratum in

No abstract available

Keywords: DOACs; NOACs; apixaban; dabigatran; edoxaban; rivaroxaban.

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Figures

Figure 1
Figure 1
Selection of possibilities to increase adherence to NOACs. AF, atrial fibrillation; NOAC, non-vitamin K antagonist oral anticoagulant.
Figure 2
Figure 2
The EHRA NOAC card. A patient information card is crucial, both for the patient (instructions on correct intake; contact information in case of questions) as for healthcare providers. This generic and universal card should document each visit, each relevant observation or examination, and any medication change. EHRA, European Heart Rhythm Association; NOAC, non-vitamin K antagonist oral anticoagulant.
Figure 3
Figure 3
Initiation and structured follow-up of patients on NOACs. It is crucial to ensure a structured follow-up of patients on NOACs. The anticoagulation card, as proposed in Figure 2, is intended to document each visit so that every person following up on the patient is well-informed. Moreover, written communication between different healthcare providers is required to inform them about the follow-up plan and execution. AF, atrial fibrillation; CrCl, creatinine clearance; GP, General Practitioner; NOAC, non-vitamin K antagonist oral anticoagulant.
Figure 4
Figure 4
Switching between NOACs and other anticoagulants. ACS, acute coronary syndrome; BID, twice daily; INR, international normalized ratio; LMWH, low molecular weight heparin; NOAC, non-vitamin K antagonist oral anticoagulant; QD, once daily; UFH, unfractionated heparin; VKA, vitamin K antagonist.
Figure 5
Figure 5
Absorption and metabolism of the different NOACs. There are interaction possibilities at the level of absorption or first transformation, and at the level of metabolization and excretion. aAlso via CYP1A2, CYP2J2, CYP2C8, CYP2C9, and CYP2C19. NOAC, non-vitamin K antagonist oral anticoagulant.
Figure 6
Figure 6
NOAC selection based on drug–drug interactions and/or risk of bleeding. Dose reduction of all NOACs is primarily recommended along the published dose reduction criteria (see ‘NOAC eligibility and dosing' section, Table 2). Whenever possible, the tested and approved dosing regimen of NOACs should be used. See text for details. *Use of plasma level measurements to guide dosing is generally discouraged and should only be used in rare cases of potentially substantial interactions or special situations, and only in centers with great experience in the performance and interpretation of such assays as well as the care of NOAC-treated patients (see ‘NOAC plasma level measurements: technical approach, indications, pitfalls' section). BID, twice daily; NOAC, non-vitamin K antagonist oral anticoagulant; PK, pharmacokinetic; RCT, randomized clinical trial; VKA, vitamin K antagonist.
Figure 7
Figure 7
Use of NOACs according to renal function. a110 mg BID in patients at high risk of bleeding (per SmPc). bOther dose reduction criteria may apply (weight ≤ 60 kg, concomitant potent P-Gp inhibitor therapy). According to EMA, SmPc edoxaban should be used in ‘high CrCl only after a careful evaluation of the individual thromboembolic and bleeding risk’. See text for details. c2 × 2.5 mg only if at least two out of three fulfilled: age ≥80 years, body weight ≤60 kg, creatinine ≥1.5 mg/dL (133 µmol/L). Orange arrows indicate cautionary use; see text for details. BID, twice daily; CrCl, creatinine clearance; EMA, European Medicines Agency; NOAC, non-vitamin K antagonist oral anticoagulant; RCT, randomized clinical trial; VKA, vitamin K antagonist.
Figure 8
Figure 8
NOACs in patients with liver disease. APTT, activated prothrombin time; INR, international normalized ratio; NOAC, non-vitamin K antagonist oral anticoagulant; NSAID, non-steroidal anti-inflammatory drug; OTC, over-the-counter; PT, prothrombin time.
Figure 9
Figure 9
Management of bleeding in patients taking NOACs. aPCC, activated prothrombin complex concentrates; NOAC, non-vitamin K antagonist oral anticoagulant; NSAID, non-steroidal anti-inflammatory drug; OTC, over-the-counter; PCC, prothrombin complex concentrates; RBC, red blood cell; WBC, white blood cell.
Figure 10
Figure 10
Application and effect of idarucizumab and andexanet alpha. Per Andexanet Alpha SmPc.  aOr unknown. Andexanet alpha is currently only approved for reversal of life-threatening uncontrollable bleeding in patients taking apixaban or rivaroxaban. In view of the very similar mode of action and preliminary subanalyses from the ANNEXA-4 trial (Benz et al., presented at at the International Stroke Conference meeting 2021), it can be assumed that it will have a similar effect in patients on edoxaban. The edoxaban dosing provided in this scheme is based on the (final) protocol of the ANNEXA-4 trial. dTT, diluted thrombin time.
Figure 11
Figure 11
(Re-) initiation of anticoagulation after GI bleeding. aWithout RCT evidence; ideally include patient in ongoing trial. GI, gastrointestinal; LAA, left atrial appendage; NOAC, non-vitamin K antagonist oral anticoagulant.
Figure 12
Figure 12
NOAC management in the setting of unplanned surgery. aPTT, activated prothrombin time; dTT, diluted thrombin time; NOAC, non-vitamin K antagonist oral anticoagulant; PT, prothrombin time.
Figure 13
Figure 13
Perioperative NOAC management. NOAC, non-vitamin K antagonist oral anticoagulant; NSAID, non-steroidal anti-inflammatory drug.
Figure 14
Figure 14
Timing of last NOAC intake before an elective intervention. CrCl, creatinine clearance; LMWH, low molecular weight heparin; NOAC, non-vitamin K antagonist oral anticoagulant; UFH, unfractionated heparin.
Figure 15
Figure 15
Stopping and re-initiation of NOAC therapy in elective surgery. Yellow star—Time point of the intervention/operation. Parentheses indicate optional pre-/postoperative intake, especially in patients not at high risk of drug accumulation/bleeding. Consider +24 h of interruption in situations likely resulting in increased plasma levels [e.g. body weight < 50 kg, significant interactions (see ‘Pharmacokinetics and drug-drug interactions of NOACs' section)]. *Intake of this dose of dabigatran if CrCl is in the indicated range; otherwise skip this dose. **Consider measurement of plasma levels in very special situations, e.g. highest risk neurosurgery/cardiac surgery, severely impaired renal function, combination of factors predisposing to higher NOAC levels (see ‘NOAC plasma level measurements: technical approach, indications, pitfalls' section). Rivaroxaban needs to be taken with food for stroke prevention in AF, which needs to be considered (also) in the post-operative setting. AF, atrial fibrillation; CrCl, creatinine clearance; NOAC, non-vitamin K antagonist oral anticoagulant.
Figure 16
Figure 16
NOAC management before and after AF ablation. ACT, activated clotting time; AF, atrial fibrillation; NOAC, non-vitamin K antagonist oral anticoagulant; TSP, transseptal puncture.
Figure 17
Figure 17
Anticoagulation therapy after elective PCI or ACS in patients with AF. ‘Shorten/de-intensify’: e.g. discontinuing Aspirin or P2Y12 inhibitor at an earlier stage. ‘Lengthen/intensify’: e.g. continuing triple combinations longer, or continuing P2Y12 inhibitor longer. A: aspirin 75–100 mg QD; C: clopidogrel 75 mg QD; Tica: Ticagrelor 90 mg BID. *If triple therapy needs to be continued after discharge clopidogrel is preferred over ticagrelor (due to lack of data). ACS, acute coronary syndrome; AF, atrial fibrillation; BID, twice daily; BMS, bare metal stent; DES, drug-eluting stent; LAD, left anterior descending artery; MI, myocardial infarction; NOAC, non-vitamin K antagonist oral anticoagulant; PCI, percutaneous coronary intervention; PPI, proton pump inhibitor; QD, once daily.
Figure 18
Figure 18
Acute management of elective PCI or ACS in AF patients treated with NOAC. ACS, acute coronary syndrome; ACT, activated clotting time; AF, atrial fibrillation; aPTT, activated prothrombin time; BMS, bare metal stent; CCS, chronic coronary syndrome; DES, drug-eluting stent; LMWH, low molecular weight heparin; NOAC, non-vitamin K antagonist oral anticoagulant; NSTE-ACS, non-ST-elevation acute coronary syndrome; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction; UFH, unfractionated heparin.
Figure 19
Figure 19
Cardioversion workflow in AF patients treated with NOAC, depending on the duration of the arrhythmia and prior anticoagulation. AF, atrial fibrillation; CV, cardiovascular; LA, left atrium; LAA, left atrial appendage; NOAC, non-vitamin K antagonist oral anticoagulant.
Figure 20
Figure 20
Acute management of acute ischaemic stroke with relevant neurological deficit in a patient on NOAC. aSystemic thrombolysis only indicated if there are no (other) contra-indications for intravenous application of rt-PA according to its label. bEndovascular thrombectomy only indicated if there is a target vessel occlusion and procedure is indicated and feasible according to present evidence. cAccording to expert consensus. NOAC, non-vitamin K antagonist oral anticoagulant.
Figure 21
Figure 21
(Re-) initiation of anticoagulation after TIA/stroke. Without proven evidence/RCT data available, based on expert opinion. Consider inclusion of patient in an ongoing trial. (Re-)start only in the absence of contraindications and if stroke size is not expected to substantially increase the risk of secondary haemorrhagic transformation. Consider shorter delays to (re-)start a NOAC in case of a very high risk of stroke recurrence [e.g. LA(A) thrombus] and no haemorrhagic transformation on follow-up brain imaging (using CT or MRI). CT, computed tomography; LA, left atrium; LAA, left atrial appendage; MRI, magnetic resonance imaging; NOAC, non-vitamin K antagonist oral anticoagulant; RCT, randomized clinical trial; TIA, transient ischaemic attack.
Figure 22
Figure 22
(Re-) initiation of anticoagulation post intracranial bleeding. aWithout RCT evidence; ideally include patient in an ongoing trial. bBrain imaging mandatory before (re-)initiation of (N)OAC. NOAC, non-vitamin K antagonist oral anticoagulant; PCI, percutaneous coronary intervention.
Figure 23
Figure 23
NOACs in under- and overweight patients. See text for details. BMI, body mass index; NOAC, non-vitamin K antagonist oral anticoagulant; VKA, vitamin K antagonist; RCT, randomized clinical trial.
Figure 24
Figure 24
NOACs in patients with thrombocytopenia. NOAC, non-vitamin K antagonist oral anticoagulant.
Figure 25
Figure 25
Important aspects in the management of AF patients with malignancies. AF, atrial fibrillation; LMWH, low molecular weight heparin; NOAC, non-vitamin K antagonist oral anticoagulant; PPI, proton pump inhibitor; VKA, vitamin K antagonist.
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Comment in

References

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