Anticoagulation guidelines

European Society of Cardiology (ESC) and the European Heart Rhythm Association (EHRA) guidelines

What are the top three most important ESC updates to implement in clinical practice?

Short on time? Join Professor John Camm to hear all the important changes to the new ESC AF guidelines that you need to implement into clinical practice, including the new CC (Confirm and Characterise AF) to ABC (Atrial Fibrillation Better Care) approach for AF diagnosis and management and the 4S-AF scheme for the structured characterisation of AF.

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Treating postoperative AF patients at risk for stroke after non-cardiac surgery and key stroke prevention and AF highlights at ESC 2020

ESC 2020 shared a wide range of fascinating abstracts and presentations that gave important insights into atrial fibrillation and the prevention of thromboembolism. In this video, hear about the updates from the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4) with Professor John Camm.

Key changes to the ESC AF guidelines?

Update your knowledge of the European guidelines regarding the use of oral anticoagulants to prevent thromboembolism in AF patients.

The ESC/EHRA guidelines suggest using the CC (Confirm and Characterise AF) to ABC (Atrial Fibrillation Better Care) approach for AF diagnosis and management (Figure 1). CC-ABC involves characterisation of the disease using the 4S-AF scheme (stroke risk, symptom severity, burden severity and substrate severity) and management based on the recognised ABC pathway of ‘A’ Anticoagulation/Avoid stroke, ‘B’ Better symptom control and ‘C’ Comorbidities/Cardiovascular risk factor management.

Figure 1. 4S-AF scheme as an example of structured characterization of AF (Adapted¹). AF, atrial fibrillation; CHA2DS2-VASc, Congestive heart failure, Hypertension, Age (>65 = 1 point, >75 = 2 points), Diabetes mellitus, Stroke/transient ischemic attack (2 points) Vascular disease (peripheral arterial disease, previous myocardial infarction, aortic atheroma), and Sex category (female gender); CT, computed tomography; EHRA, European Heart Rhythm Association; LA, left atrium; MRI, magnetic resonance imaging; QoL, quality of life; TOE, transoesophageal echocardiography; TTE, transthoracic echocardiography. 

ESC AF guidelines for stratifying patients based on risk

The ESC/EHRA guidelines state that the HAS-BLED score should be considered as a formal assessment to help address modifiable bleeding risk factors and identify patients at high risk of bleeding (HAS-BLED score ≥3) for early and more frequent clinical review and follow-up.

In addition,

periodic assessments of both stroke and bleeding risk are recommended to inform treatment decisions (e.g., initiation of OAC in patients no longer at low risk of stroke) and address potentially modifiable bleeding risk factors.

As part of the CC to ABC approach, the ‘AF 3-step’ pathway gives a guide to determining which patients should be considered for oral anticoagulation (Figure 2).

In patients receiving a vitamin K antagonist (VKA) with a low time in INR therapeutic range (e.g., time in therapeutic range [TTR] <70%), the guidelines recommend either improving TTR with efforts to increase education or INR check frequency or switching to a DOAC and ensuring good adherence and persistence with therapy.

The guidelines recommend oral anticoagulants to prevent thromboembolism for all male AF patients with a CHA2DS2-VASc score of 2 or more and all female patients with a CHA2DS2-VASc score of 3 or more, with treatment individualised based on net clinical benefit and patient values or preferences. The ESC/EHRA also suggest that oral anticoagulation should be considered in patients with a CHA2DS2-VASc score of 1 in men or 2 in women, but not in patients at low risk (CHA2DS2-VASc score of 0 or 1, respectively).

Patients with AF identified as low-risk of stroke should be reassessed at 4-6 months after the index event¹. For AF patients who are eligible, the ESC/EHRA guidelines recommend a DOAC in preference to a VKA. However, the guidelines recommend warfarin or another VKA to prevent stroke in AF patients with moderate-to-severe mitral stenosis or mechanical heart valves; time in the therapeutic range should be ≥70% and monitored closely¹.

Guidelines also recommend switching to a DOAC for patients currently receiving warfarin or another VKA if the time in the therapeutic range is poorly controlled (TTR <70%). Patients currently receiving a VKA can discuss switching to a DOAC provided they do not have contraindications, such as a prosthetic valve1. A risk score-based bleeding risk assessment (e.g., HAS-BLED) is also recommended to identify patients at high risk of bleeding who should be scheduled for more frequent clinical follow-up. Estimated bleeding risk, in the absence of absolute contraindications to OAC, should not in itself guide treatment decisions to avoid using OAC.

Antiplatelet therapy alone, such as monotherapy or aspirin in combination with clopidogrel, is not recommended for stroke prevention in AF.

Figure 2. ‘A’ - Anticoagulation/Avoid stroke: The ‘AF 3-step’ pathway (Adapted¹). AF, atrial fibrillation; CHA2DS2-VASc, Congestive heart failure, Hypertension, Age (>65 = 1 point, >75 = 2 points), Diabetes mellitus, Stroke/transient ischemic attack (2 points) Vascular disease (peripheral arterial disease, previous myocardial infarction, aortic atheroma), and Sex category (female gender); HAS-BLED, Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly (>65 years), Drugs/alcohol concomitantly; INR, international normalised ratio; NOAC, non-vitamin K antagonist oral anticoagulant; OAC, oral anticoagulant; SAMe-TT2R2, Sex (female), Age (<60 years), Medical history, Treatment (interacting drug(s)), Tobacco use, Race (non-Caucasian) (score); TTR, time in therapeutic range; VKA, vitamin K antagonist. aIf a VKA being considered, calculate SAMe-TT2R2 score: if score 0-2, may consider VKA treatment (e.g. warfarin) or NOAC; if score >2, should arrange regular review, frequent INR checks, and counselling for VKA users to help good anticoagulation control, or reconsider the use of NOAC instead; TTR ideally >70%. 

ESC/EHRA warnings

The ESC/EHRA guidelines warn that combining oral anticoagulants and antiplatelet medications increases bleeding risk and should be avoided in AF patients, unless they have another indication for platelet inhibition. The guidelines also advise against using oral anticoagulants and antiplatelets for stroke prevention in AF patients who do not have additional cerebrovascular risk factors, and do not recommend antiplatelet monotherapy to prevent stroke in AF patients due to a substantial increase in the risk of major bleeding and intracranial haemorrhage, irrespective of the cerebrovascular risk¹

Secondary stroke prevention

In patients with AF and prior ischaemic stroke or TIA, long-term prevention of a secondary stroke should be managed using oral anticoagulation, with a preference for DOACs in eligible patients rather than a VKA. Following a trauma-related or spontaneous ICH, secondary stroke prevention in AF patients at high risk of ischaemic stroke should include starting, or re-starting, OAC (with preference for DOACs over VKAs) following consultation with a neurologist/stroke specialist¹.

Where acute ischaemic stroke occurs despite OAC management, treatment optimisation is critical. Patients receiving a VKA should be managed to attain a TTR >70% or switched to a DOAC. In the event that the patient is already receiving a DOAC, appropriate dosing and good adherence should be ensured. Inappropriate under-dosing of DOACS has been associated with increased risk of stroke/systemic embolism, hospitalisation, and deaths without appreciable reduction in major bleeding.

Key warnings

The ESC/EHRA guidelines do not recommend anticoagulation with heparin, low molecular weight heparin, or a VKA immediately after an ischaemic stroke for AF patients. Adherence assessment and optimisation with anticoagulants are recommended for AF patients experiencing a TIA or stroke while taking warfarin or a DOAC¹

Stroke prevention in patients designated for undergoing invasive treatment

The ESC/EHRA guidelines recommend anticoagulation with heparin or a DOAC as soon as possible (minimum of 3 weeks) before cardioversion of AF or atrial flutter. Transoesophageal echocardiography to exclude cardiac thrombus is a recommended alternative to anticoagulation if early cardioversion is planned. Early cardioversion of AF with a definite duration of less than 48 hours can be performed without transoesophageal echocardiography¹.

Anticoagulation is recommended for at least 3 weeks if transoesophageal echocardiography reveals a thrombus. Clinicians should consider repeating the transoesophageal echocardiography before cardioversion. Patients at risk for stroke should receive long-term anticoagulant therapy after cardioversion, irrespective of the method or maintenance of sinus rhythm. AF patients without stroke risk factors, should receive anticoagulation for 4 weeks following cardioversion¹.

Stroke prevention in AF patients requiring anticoagulation after ACS or undergoing PCI

In AF patients with acute coronary syndrome (ACS) undergoing an uncomplicated percutaneous coronary intervention (PCI), the ESC/EHRA guidelines suggest long-term dual antithrombotic therapy including OAC (preferably a DOAC) and a P2Y12 inhibitor (preferably clopidogrel).

However, at least a short course of triple therapy with aspirin, a P2Y12 inhibitor (preferably clopidogrel) clopidogrel, and an OAC (preferably a DOAC) may be desirable for some AF patients after undergoing PCI, especially where there is an increased risk of ischaemic events.

Figure 3. Stroke prevention in AF patients with ACS and/or PCI (Adapted¹). ACS, acute coronary syndromes; CCS, chronic coronary syndromes; INR, international normalised ratio; NOAC, non-vitamin K antagonist oral anticoagulant; OAC, oral anticoagulant; PCI, percutaneous coronary intervention.

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More on the treatment options for AF

With guidelines now considering the evidence from clinical trials such as the AUGUSTUS trial we are moving towards harmonisation of American and European guidelines.

More on the treatment options for AF

American College of Cardiology (ACC), American Heart Association (AHA) and Heart Rhythm Society (HRS) guidelines

Update your knowledge of the American recommendations regarding the use of oral anticoagulants to prevent thromboembolism in AF patients.

The guidelines from the USA recommend oral anticoagulants for AF (or atrial flutter) patients with a CHA₂DS₂-VASc score of two or greater in men or three or greater in women. Unless, the person has moderate-to-severe mitral stenosis or a mechanical heart valve, the guidelines remark that omitting anticoagulants is reasonable for AF patients CHA₂DS₂-VASc score of zero in men or one in women, but can be considered in those with scores of one and two respectively².

The guidelines recommend DOACs rather than warfarin in eligible AF patients, with the exception of those with moderate-to-severe mitral stenosis or a mechanical heart valve. Warfarin is recommended for AF patients with mechanical heart valves. The guidelines note that the trials suggest that DOACs were non-inferior and, in some trials, superior to warfarin for preventing stroke and systemic embolism. In addition, DOACs were associated with lower risks of serious haemorrhage compared with warfarin².

The ACC/AHA/HRS guidelines recommend the CHA₂DS₂-VASc score to assess stroke risk in AF patients, except people with moderate-to-severe mitral stenosis or a mechanical heart valve. The 2021 AHA/ASA guideline for prevention of stroke in patients with stroke and transient ischemic attack (TIA), recommends that DOACs should not be used in patients with moderately severe or greater mitral stenosis or a mechanical heart valve³. The guidelines stress that the decision to use anticoagulants depends on the risk of thromboembolism, irrespective of the AF pattern and should be individualised based on shared decision-making after discussing the absolute and relative risks of stroke and haemorrhage, and the patient’s values and preferences. Clinicians and patients should periodically re-evaluate the need for a choice of anticoagulant based on the risk of stroke and haemorrhage².

The ACC/AHA/HRS guidelines underscore the importance of regularly monitoring patients taking warfarin. The guidelines suggest determining INR at least weekly during initiation of warfarin therapy and at least monthly when anticoagulation is stable, with the INR in range. The guidelines recommend a DOAC for patients that cannot maintain a therapeutic INR with warfarin, unless the person is ineligible because of moderate-to-severe mitral stenosis or a mechanical heart valve².

Clinicians should evaluate renal and hepatic function before starting a DOAC. The guidelines recommend re-evaluating renal and hepatic function at least annually²:

• For AF patients with end-stage CKD, defined as creatinine clearance of less than 15 mL/minute or dialysis, and a CHA₂DS₂-VASc score of 2 or greater in men or 3 or greater in women, the guidelines suggest apixaban or warfarin
• For AF patients (except those with moderate-to-severe mitral stenosis or a mechanical heart valve) and moderate-to-severe CKD and a CHA₂DS₂-VASc score of 2 or greater in men or 3 or greater in women, the guidelines suggest considering reduced doses of direct thrombin or factor Xa inhibitors; the definition of moderate-to-severe CKD depends on the DOAC: serum creatinine at least 1.5 mg/dL for apixaban and creatinine clearances of 15–30 mL/minute for dabigatran, at least 50 mL/ minute for rivaroxaban or 15–50 mL/ minute for edoxaban
• The guidelines do not recommend dabigatran, rivaroxaban or edoxaban for AF patients with end-stage CKD or on dialysis as the evidence from clinical trials does not confirm that the benefit exceeds risk

Stroke prevention in patients with AF and ACS and/or PCI

US guidelines treat these patients as one specific group². Patients treated for ACS normally require dual antiplatelet therapy with aspirin and may also require the addition of warfarin or a DOAC (triple therapy). Double therapy (DOAC plus an antiplatelet medication without aspirin) can also be considered. Indeed, the US guidelines recommend that triple therapy is limited to 4–6 weeks as this is the period of greatest risk of thrombosis following PCI, especially in patients with ACS².

Atrial fibrillation – the ABC pathway in clinical practice

The 2020 European Society of Cardiology guidelines endorse the Atrial Fibrillation Better Care (ABC) pathway as a structured approach for the management of atrial fibrillation (AF), structured around three principal elements: 'A' - avoid stroke (with oral anticoagulation), 'B' - patient-focused better symptom management, and 'C' - cardiovascular and comorbidity risk factor reduction and management. The ABC pathway provides a simple decision-making framework to enable a consistent gold-standard of care from health care practitioners (HCPs). In this section, Dr. Marco Proietti, will discuss the ABC pathway in clinical practice, demonstrating real-world data for its efficiency in improving patient outcomes.

In the 24,608 patients from GLORIA-AF, adherence to ABC was associated with significant risk reduction (adjusted Hazard Ratio [aHR] 0.54, 95% Confidence Interval [CI]: 0.44–0.67, p < 0.0001), reduced risk of mortality y (aHR: 0.89, 95% CI: 0.79–1.00, p = 0.048), thromboembolism (aHR: 0.78, 95% CI: 0.65–0.94, p = 0.0078), and MACE (aHR: 0.82, 95% CI: 0.71–0.95, p = 0.0071)⁴.

References

1. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Euro Heart J. 2021;42(5):373–498.
2. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart R. Circulation. 2019;140(2):e125-e151.
3. Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021;52(7).
4. Romiti GF, Proietti M, Bonini N, Ding WY, Boriani G, Huisman MV, et al. Adherence to the Atrial Fibrillation Better Care (ABC) pathway and the risk of major outcomes in patients with atrial fibrillation: a post-hoc analysis from the prospective GLORIA-AF Registry. eClinicalMedicine. 2023;55:101757.