Atrial fibrillation anticoagulation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]Cafer Zorkun, M.D., Ph.D. [3] George Leef, MD; Arzu Kalayci, M.D. [4], Syed Hassan A. Kazmi BSc, MD [5]; Sabawoon Mirwais, M.B.B.S, M.D.[6]

Overview

Oral anticoagulation is used to prevent stroke and systemic embolization and is considered a mainstay of atrial fibrillation management. Anticoagulation is recommended for atrial fibrillation (AF) patients who are at high risk for stroke based on CHADS2-VASc score who do not have an unacceptable risk of bleeding (HAS-BLED score). Treatment with anticoagulation can be done with one the novel oral anticoagulants (NOACs), or warfarin. Four novel oral anticoagulants (NOACs) have been approved for use in nonvalvular atrial fibrillation (AF) as alternatives to warfarin. Anti-platelet therapy is not recommended for stroke reduction in atrial fibrillation (AF).^[1]

Atrial fibrillation anticoagulation

Anticoagulation therapy is a critical part of treatment in patients with atrial fibrillation who have considerable stroke risk. The treatment is focused on decreasing the risk of thrombosis formation without increasing the risk of bleeding. To measure both risks there are two scores, explained below; CHADS2-VASc. Without proper anticoagulation treatment, rates of death due to stroke will be high among atrial fibrillation patients.^[2]^[3]

CHADS2-VASc score For more information regards CHA2DS2-VASc Score click here

The CHA2DS2-VASc score is currently the recommended system for estimating stroke risk in patients with AF.^[4]^[5] Points are assigned as follows:
- Congestive Heart Failure : 1 point
- Hypertension : 1 point
- Age > 75 : 2 point
- Diabetes : 1 point
- Stroke/TIA : 2 points
- Vascular disease (CAD, PAD) : 1 point
- Age 65-74 : 1 point
- Female sex 1 point
The following is a summary of score prevention based on National Institute for Health and Care Excellence (NICE) guideline: ^[5]

Calculate the CHA2DS2-VASc score

CHA2DS2-VASc score > 2

CHA2DS2-VASc score of 1 in males

CHA2DS2-VASc score of 1 in females OR CHA2DS2-VASc score of zero

Offer oral anticoagulant

Consider direct oral anticoagulant
In the presence of any contraindications or when direct oral anticoagulant is not tolerated vitamin K antagonist should be considered

Treatment with an anticoagulant is not required.

Follow up these patients again (at age 65 and 75 or when diabetes, stroke or other vascular diseases develop)

Anticoagulation Treatment Summary for Acute Atrial Fibrillation - NICE Guideline

The following algorithm is a summary of acute atrial fibrillation management, based on NICE guideline 2021:^[5]

Acute Atrial Fibrillation

New-onset atrial fibrillation

Previously diagnosed AF with shorter than 48 hours onset

New-onset atrial fibrillation with unknown time of onset

Offer heparin in the absence of contraindications

Offer oral anticoagulation if:
There is high chance of AF recurrence (such as previous history of unsuccessful cardioversion, structural heart disease and long-lasting AF (>12 months))
Unsuccessful sinus rhythm restoration within 48 hours of AF onset
Access stroke and bleeding risk to evaluate risks and benefits

Offer oral anticoagulation after assessing the risk and benefits of anticoagulation

Heparin must be continued until proper risk assessment for bleeding and stroke, then it should be replaced with a proper antithrombotic therapy

It is not recommended to discontinue anticoagulant therapy in previously diagnosed atrial fibrillation patients due to undetectable fibrillation alone. The only recommended method to discontinue anticoagulant therapy is to reassess stroke and bleeding risk based on CHA2DS2-VASc and ORBIT scores respectively.^[5]

Anticoagulation Options

Novel Oral Anticoagulants

Since 2010, four novel oral anticoagulants (NOACs) have been approved. These are direct inhibitors of thrombin (factor II) or factor Xa. Unlike warfarin, they have quick onset, short half life, do not require INR monitoring, have fewer drug-drug and food interactions, and favorable safety profiles. The NOACs are approved for use in nonvalvular atrial fibrillation only.
- Apixaban:
  - factor Xa inhibitor, may be the best choice^[6].
  - Compared to warfarin in ARISTOTLE trial ^[7].
  - Apixaban was found to have superior stroke protection and lower risk for major bleeding. Notably ARISTOTLE showed a decrease in total deaths compared to warfarin, which has not been seen with any other NOAC.
- Dabigatran:
  - Direct thrombin inhibitor, compared to warfarin in RE-LY trial ^[8].
  - Dabigatran was found to have comparable stroke protection and lower risk for major bleeding, especially intracranial bleeding.
- Rivaroxaban:
  - Factor Xa inhibitor, compared to warfarin in ROCKET-AF trial ^[9].
  - Rivaroxaban was found to have comparable stroke protection and similar risk for major bleeding. Risk of intracranial bleeding was lower with rivaroxaban.
- Edoxaban:
  - Factor Xa inhibitor, compared to warfarin in ENGAGE trial ^[10].
  - Edoxaban was found to have comparable stroke protection and lower risk for major bleeding.
  - [Edoxaban]] was found to be inferior to warfarin for stroke prevention in patients with CrCl >95mL/min based on subgroup analysis, so it is only approved for patients with CrCl between 30-95.
None of the NOACs have been tested in patients with severe renal impairment. Dabigatran was tested in patients with mechanical valves in the RE-ALIGN trial ^[11], but the trial had to be stopped early due to excess thrombotic events in the dabigatran arm. All NOACs are considered contraindicated in valvular atrial fibrillation.

Warfarin

- Warfarin is the traditional oral anticoagulant used in atrial fibrillation. For both primary and secondary prevention of stroke, there is a 61% relative risks reduction in the incidence of all cause stroke (both ischemic and hemorrhagic) associated with adjusted-dose warfarin.^[12]
- An INR between 2-3 has been found to be best for reducing stroke risk while balancing against bleeding risk.^[12]^[13]^[14] ^[12]^[15]
- The optimal INR should obviously maximize efficacy in reducing the risk of stroke and simultaneously minimize the risk of bleeding. INRs lower than this, such as those in the range of 1.6 to 2.5, are associated with efficacy that is only 80% of that in the target range.^[16]^[17] ^[18]^[19]
- There are a number of problems with warfarin, including the high level of monitoring required and the numerous interactions with food and other medications.
- In stable patients who are on vitamin K antagonists such as warfarin it is recommended to continue the treatment. Nevertheless offering other options at their next routine appointment should be considered. ^[5]

Antiplatelet Therapy for Atrial Fibrillation (not recommended)

Aspirin Monotherapy

Aspirin monotherapy is associated with only a modest and inconsistent reduction in the risk of stroke associated with atrial fibrillation.^[19]^[20]
Studies suggest that the efficacy of aspirin may be greater in patients with hypertension or diabetes.
Aspirin may also be more efficacious in reducing the risk of non-cardioembolic stroke as opposed to the more disabling cardioembolic form of stroke. Nevertheless it's sole usage in order to stroke prevention is not recommended.^[21]^[22]^[5]
Apixaban was compared to aspirin for prevention of stroke in the AVERROES trial, which showed that apixaban was more effective than aspirin for stroke prevention with a comparable bleeding risk. ^[23].
There are not sufficient reasons to use aspirin monotherapy in atrial fibrillation given the availability of clearly superior alternatives.

Dual Antiplatelet Therapy

Among patients who are not deemed candidates for Coumadin therapy (estimated to be approximately 40-50% of patients), dual antiplatelet therapy with both aspirin and clopidogrel (at a maintenance dose of 75 mg/day) was superior to aspirin monotherapy in the ACTIVE-A trial. The primary endpoint of the trial was the composite of stroke, myocardial infarction, non–central nervous system systemic embolism, or death from vascular causes. After a median of 3.6 years of follow-up in 7,554 randomized patients, the addition of clopidogrel to aspirin alone yielded a reduction in events from 7.6% to 6.8% (relative risk reduction with clopidogrel, 0.89; 95% confidence interval (CI), 0.81 to 0.98; P=0.01). The addition of clopidogrel to aspirin alone reduced the risk of stroke by 28% (from 3.3% to 2.4%, p<0.001) and reduced the risk of myocardial infarction by 22% (from 0.9% per year to 0.7% per year, p=0.08).
The risk of major bleeding among patients treated with aspirin and clopidogrel was 2.0% per year whereas it was 1.3% per year among patients treated with aspirin alone (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001). If 1000 patients were treated for 3 years, the combination of aspirin plus clopidogrel would prevent 28 strokes (17 disabling or fatal), and 6 myocardial infarctions, at a cost of 20 major bleeds compared to aspirin alone.
These trials were all conducted in the pre-NOAC era. With the availability of alternatives to warfarin, there should be very few patients who cannot take anticoagulation. Dual antiplatelet therapy is not routinely recommended.

Anticoagulation in end stage renal disease

Patients with end stage renal disease were excluded from the trials of warfarin in atrial fibrillation, as well as from the trials of the NOACs in atrial fibrillation.
There is no high quality randomized data looking at anticoagulation in patients with atrial fibrillation and end stage renal disease.
Given the risk factors for kidney disease, most patients with atrial fibrillation and end stage renal disease will have high CHADS2-VASc scores as well as high HAS-BLED scores.
Several observational studies have suggested that warfarin may not be beneficial in end stage renal disease given a markedly increased risk for intracranial bleeding ^[24]^[25]^[26]^[27].
This may be related to baseline bleeding propensity in end stage renal disease from uremic platelet dysfunction as well as issues with maintaining a therapeutic INR.
Use of warfarin in end stage renal disease patients requires additional study and higher quality data, but based on current data it is not clearly beneficial.
AHA/ACC still gives warfarin a weak recommendation in dialysis patients based on the 2014 guidelines, but KDIGO recommends against routine anticoagulation in dialysis patients given the uncertainty that benefits outweigh risks.
Warfarin is still necessary in very high risk situations, such as mechanical valve or known left ventricle thrombus.
There is no clear alternative to warfarin, since low molecular weight heparin is cleared by the kidney and the novel oral anticoagulants have not been studied in advanced kidney disease.
Apixaban has dosing recommendations in ESRD, but these are based on pharmacokinetic data only. Currently there is no published outcomes data for apixaban in advanced kidney disease.

Anticoagulation Reassessment

Based on NICE guideline updated in 2021 the following are indications for reassessing the anticoagulation treatment in the patients who are under treatment:^[5]

If there are 2 INR measures higher than 5 or only one INR measure higher than 8 within the last 6 months
If there are 2 INR measures lower than 1.5 within the last 6 months
Time in therapeutic range (TTR) lower than 65%

In order to have a safe anticoagulation treatment, NICE guideline recommends to evaluate the following factors when anticoagulation reassessment is considered:^[5]

Adherence to therapy
Cognitive function
Other illnesses
Possible drug interaction
Lifestyle of the patients such as their diet and alcohol consumption

Interruption of Anticoagulation

In patients with no mechanical valve and high risk of bleeding with procedures coumadin can be discontinued for one week without heparin bridging.
In presence of mechanical valve, patients with atrial fibrillation who are at high risk of stroke, or patients in whom coumadin must be interrupted for over a week either unfractionated heparin or low molecular weight heparin should be administered.

2019 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline


Class of Recommendation	Recommendation	Comment/Rationale
I	Oral anticoagulants recommended for high risk patients now have edoxaban included Exclusion criteria for CHA2DS2-VASc assessment and use of NOACs now defined as moderate to severe mitral stenosis or a mechanical heart valve For atrial fibrillation or atrial flutter of greater than or equal to 48 hours or of unknown duration, anticoagulation with warfarin (INR 2-3), a factor Xa inhibitor or direct oral anticoagulant is recommended for at least 3 weeks before and at least 4 weeks after cardioversion NOACs are recommended over warfarin where eligible except in those patients with moderate - severe mitral stenosis or a mechanical heart valve Idarucizumab is the reversal agent for dabigatran in the event of life-threatening bleeding or an urgent procedure In patients with cardiac implantable electronic devices, atrial high rate episodes (AHREs) should prompt further evaluation Weight loss and risk factor modification is recommended for overweight/obese patients with atrial fibrillation. Further evaluation should be performed in patients with AHREs who have received cardiac implantable electronic devices Weight loss and risk factor modification is recommended for overweight/obese patients with atrial fibrillation.
IIa	For patients with atrial fibrillation or atrial flutter of <48 hours' duration with a CHA2DS2-VASc score of ≥2 in men and ≥3 in women: Heparin, a factor Xa inhibitor, or a direct thrombin inhibitor as close to starting cardioversion Long term anticoagulation recommended after cardioversion Andexanet alfa recommended as a reversal agent for apixaban and rivaroxaban induced bleeding episodes Catheter ablation of atrial fibrillation is reasonable in symptomatic atrial fibrillation patients with heart failure and reduced left ventricle ejection fraction. Clopidogrel preferred over prasugrel as a part of triple therapy post-stenting Double therapy with a P2Y12 inhibitor and dose adjusted vitamin K antagonist is reasonable post-stenting Double therapy with clopidogrel and low-dose rivaroxaban (15 mg daily) may be reasonable post-stenting Double therapy with a P2Y12 inhibitor and dabigatran 150 mg twice daily is reasonable post-stenting. For detection of silent atrial fibrillation in patients with cryptogenic stroke in whom long-term external ambulatory monitoring is equivocal, implantation of a [cardiology\|cardiac]] monitor is reasonable
IIb	Percutaneous left atrial appendage occlusion should be considered for those atrial fibrillation patients at an increased risk of stroke who have contraindications to long-term anticoagulation and who are at high risk of thromboembolic events. After initial 4-6 weeks of triple therapy for atrial fibrillation patients at high risk for stroke and those who have undergone percutaneous coronary intervention for stenting post-ACS, switch to double therapy should be considered
III	The direct thrombin inhibitor dabigatran should not be used in patients with atrial fibrillation and a mechanical heart valve In patients with atrial fibrillation and end-stage CKD or on dialysis, the direct thrombin inhibitor dabigatran or the factor Xa inhibitors rivaroxaban or edoxaban are not recommended because of the lack of evidence from clinical trials that benefit exceeds risk.

2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease (VHD)

Recommendation for Anticoagulation for Atrial Fibrillation (AF) in Patients with VHD

COR	LOE	RECOMMENDATION	COMMENT/RATIONALE
I	B-NR	Anticoagulation with a vitamin K antagonist (VKA) is indicated for patients with rheumatic mitral stenosis (MS) and AF.	MODIFIED: VKA as opposed to the direct oral anticoagulants (DOACs) are indicated in patients with AF and rheumatic MS to prevent thromboembolic events. The RCTs of DOACs versus VKA have not included patients with MS. The specific recommendation for anticoagulation of patients with MS is contained in a subsection of the topic on anticoagulation.
I	C-LD	Anticoagulation is indicated in patients with AF and a CHA2DS2-VASc score of 2 or greater with native aortic valve disease, tricuspid valve disease, or mitral regurgitation.	NEW: Post hoc subgroup analyses of large RCTs comparing DOAC versus warfarin in patients with AF have analyzed patients with native valve disease other than MS and patients who have undergone cardiac surgery. These analyses consistently demonstrated that the risk of stroke is similar to or higher than that of patients without VHD. Thus, the indication for anticoagulation in these patients should follow Guideline Determined Medical Therapy (GDMT) according to the CHA2DS2-VASc score.
IIa	C-LD	It is reasonable to use a DOAC as an alternative to a VKA in patients with AF and native aortic valve disease, tricuspid valve disease, or MR and a CHA2DS2-VASc score of 2 or greater.	NEW: Several thousand patients with native VHD (exclusive of more than mild rheumatic MS) have been evaluated in RCTs comparing DOACs versus warfarin. Subgroup analyses have demonstrated that DOACs, when compared with warfarin, appear as effective and safe in patients with VHD as in those without VHD.

2017 ESC/EACTS Guidelines for the Management of Atrial Fibrillation in Patients With Valvular Heart Disease (VHD)


Recommendations	Class of Recommendation	Level of Evidence
Anticoagulation
NOACs should be considered as an alternative to VKAs in patients with aortic stenosis, aortic regurgitation and mitral regurgitation presenting with atrial fibrillation^[28]	IIa	B
NOACs should be considered as an alternative to VKAs after the third month of implantation in patients who have atrial fibrillation associated with a surgical or transcatheter aortic valve bioprosthesis	IIa	C
The use of NOACs is not recommended in patients with atrial fibrillation and moderate to severe mitral stenosis	III	C
NOACS are contraindicated in patients with a mechanical valve^[29]	III	B
Surgical Interventions
Surgical ablation of atrial fibrillation should be considered in patients with symptomatic atrial fibrillation who undergo valve surgery^[30]	IIa	A
Surgical ablation of atrial fibrillation may be considered in patients with asymptomatic atrial fibrillation who undergo valve surgery, if feasible, with minimal risk	IIb	C
Surgical excision or external clipping of the LA appendage may be considered in patients undergoing valve surgery^[31]	IIb	B
LA = left atrial NOAC = non-vitamin K antagonist oral anticoagulant VHD = valvular heart disease VKA = vitamin K antagonist

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (DO NOT EDIT)^[4]

Prevention of Thromboembolism

Risk-Based Antithrombotic Therapy

Template:Seealso

Class I
"1. In patients with AF, antithrombotic therapy should be individualized based on shared decision-making after discussion of the absolute and RRs of stroke and bleeding, and the patient’s values and preferences. (Level of Evidence: C) "
"2. Selection of antithrombotic therapy should be based on the risk of thromboembolism irrespective of whether the AF pattern is paroxysmal, persistent, or permanent. (Level of Evidence: B) "
"3. In patients with nonvalvular AF, the CHA2DS2-VASc score is recommended for assessment of stroke risk. (Level of Evidence: B) "
"4. For patients with AF who have mechanical heart valves, warfarin is recommended and the target international normalized ratio (INR) intensity (2.0 to 3.0 or 2.5 to 3.5) should be based on the type and location of the prosthesis. (Level of Evidence: B) "
"5. For patients with nonvalvular AF with prior stroke, transient ischemic attack (TIA), or a CHA2DS2-VASc score of 2 or greater, oral anticoagulants are recommended. Options include: warfarin (INR 2.0 to 3.0) (Level of Evidence: A), dabigatran (Level of Evidence: B), rivaroxaban (Level of Evidence: B), or apixaban (Level of Evidence: B)."
"6. Among patients treated with warfarin, the INR should be determined at least weekly during initiation of antithrombotic therapy and at least monthly when anticoagulation (INR in range) is stable. (Level of Evidence: A) "
"7. For patients with nonvalvular AF unable to maintain a therapeutic INR level with warfarin, use of a direct thrombin or factor Xa inhibitor (dabigatran, rivaroxaban, or apixaban) is recommended. (Level of Evidence: C) "
"8. Re-evaluation of the need for and choice of antithrombotic therapy at periodic intervals is recommended to reassess stroke and bleeding risks. (Level of Evidence: C) "
"9. Bridging therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is recommended for patients with AF and a mechanical heart valve undergoing procedures that require interruption of warfarin. Decisions regarding bridging therapy should balance the risks of stroke and bleeding. (Level of Evidence: C) "
"10. For patients with AF without mechanical heart valves who require interruption of warfarin or newer anticoagulants for procedures, decisions about bridging therapy (LMWH or UFH) should balance the risks of stroke and bleeding and the duration of time a patient will not be anticoagulated. (Level of Evidence: C) "
"11. Renal function should be evaluated prior to initiation of direct thrombin or factor Xa inhibitors and should be re-evaluated when clinically indicated and at least annually. (Level of Evidence: B) "
"12. For patients with atrial flutter, antithrombotic therapy is recommended according to the same risk profile used for AF. (Level of Evidence: C) "

Class III: No Benefit
"1. The direct thrombin inhibitor, dabigatran, and the factor Xa inhibitor, rivaroxaban, are not recommended in patients with AF and end-stage CKD or on hemodialysis because of the lack of evidence from clinical trials regarding the balance of risks and benefits. (Level of Evidence: C) "

Class III: Harm
"1. The direct thrombin inhibitor, dabigatran, should not be used in patients with AF and a mechanical heart valve. (Level of Evidence: B) "

Class IIa
"1. For patients with nonvalvular AF and a CHA2DS2-VASc score of 0, it is reasonable to omit antithrombotic therapy. (Level of Evidence: B) "
"2. For patients with nonvalvular AF with a CHA2DS2-VASc score of 2 or greater and who have end-stage CKD (creatinine clearance [CrCl] <15 mL/min) or are on hemodialysis, it is reasonable to prescribe warfarin (INR 2.0 to 3.0) for oral anticoagulation. (Level of Evidence: B) "

Class IIb
"1. For patients with nonvalvular AF and a CHA2DS2-VASc score of 1, no antithrombotic therapy or treatment with an oral anticoagulant or aspirin may be considered. (Level of Evidence: C) "
"2. For patients with nonvalvular AF and moderate-to-severe CKD with CHA2DS2-VASc scores of 2 or greater, treatment with reduced doses of direct thrombin or factor Xa inhibitors may be considered (e.g., dabigatran, rivaroxaban, or apixaban), but safety and efficacy have not been established. (Level of Evidence: C) "
"3. In patients with AF undergoing percutaneous coronary intervention, bare-metal stents may be considered to minimize the required duration of dual antiplatelet therapy. Anticoagulation may be interrupted at the time of the procedure to reduce the risk of bleeding at the site of peripheral arterial puncture. (Level of Evidence: C) "
"4. Following coronary revascularization (percutaneous or surgical) in patients with AF and a CHA2DS2-VASc score of 2 or greater, it may be reasonable to use clopidogrel (75 mg once daily) concurrently with oral anticoagulants but without aspirin. (Level of Evidence: B) "

2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline) (DO NOT EDIT)^[32]

Combining Anticoagulant with Antiplatelet Therapy

Class IIb
"1. The addition of clopidogrel to aspirin (ASA) to reduce the risk of major vascular events, including stroke, might be considered in patients with AF in whom oral anticoagulation with warfarin is considered unsuitable due to patient preference or the physician’s assessment of the patient’s ability to safely sustain anticoagulation. (Level of Evidence: B) "

2010 ACCF/ACG/AHA Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines - Summary of Findings and Consensus Recommendations^[33] (DO NOT EDIT)

“

Clopidogrel reduces major CV events compared with placebo or aspirin.
Dual antiplatelet therapy with clopidogrel and aspirin, compared with aspirin alone, reduces major CV events in patients with established ischemic heart disease, and it reduces coronary stent thrombosis but is not routinely recommended for patients with prior ischemic stroke because of the risk of bleeding.
Clopidogrel alone, aspirin alone, and their combination are all associated with increased risk of GI bleeding.
Patients with prior GI bleeding are at highest risk for recurrent bleeding on antiplatelet therapy. Other clinical characteristics that increase the risk of GI bleeding include advanced age; concurrent use of anticoagulants, steroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin; and Helicobacter pylori infection. The risk of GI bleeding increases as the number of risk factors increases.
Use of a PPI or histamine H2 receptor antagonist (H2RA) reduces the risk of upper GI bleeding compared with no therapy. PPIs reduce upper GI bleeding to a greater degree than do H2RAs.
PPIs are recommended to reduce GI bleeding among patients with a history of upper GI bleeding. PPIs are appropriate in patients with multiple risk factors for GI bleeding who require antiplatelet therapy.
Routine use of either a PPI or an H2RA is not recommended for patients at lower risk of upper GI bleeding, who have much less potential to benefit from prophylactic therapy.
Clinical decisions regarding concomitant use of PPIs and thienopyridines must balance overall risks and benefits, considering both CV and GI complications.
Pharmacokinetic and pharmacodynamic studies, using platelet assays as surrogate endpoints, suggest that concomitant use of clopidogrel and a PPI reduces the antiplatelet effects of clopidogrel. The strongest evidence for an interaction is between omeprazole and clopidogrel. It is not established that changes in these surrogate endpoints translate into clinically meaningful differences.
Observational studies and a single randomized clinical trial (RCT) have shown inconsistent effects on CV outcomes of concomitant use of thienopyridines and PPIs. A clinically important interaction cannot be excluded, particularly in certain subgroups, such as poor metabolizers of clopidogrel.
The role of either pharmacogenomic testing or platelet function testing in managing therapy with thienopyridines and PPIs has not yet been established.

”

Sources

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation^[4]

ACCF/AHA/HRS 2011 Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation^[34]

ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines^[33]

ACC/AHA/Physician Consortium 2008 Clinical Performance Measures for Adults With Nonvalvular Atrial Fibrillation or Atrial Flutter^[35]

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation^[36]

References

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↑ ^4.0 ^4.1 ^4.2 January, C. T.; Wann, L. S.; Alpert, J. S.; Calkins, H.; Cleveland, J. C.; Cigarroa, J. E.; Conti, J. B.; Ellinor, P. T.; Ezekowitz, M. D.; Field, M. E.; Murray, K. T.; Sacco, R. L.; Stevenson, W. G.; Tchou, P. J.; Tracy, C. M.; Yancy, C. W. (2014). "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 Practice Guidelines and the Heart Rhythm Society". Circulation. doi:10.1161/CIR.0000000000000041. ISSN 0009-7322.
↑ ^5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 ^5.6 ^5.7 Perry M, Kemmis Betty S, Downes N, Andrews N, Mackenzie S, Guideline Committee (2021). "Atrial fibrillation: diagnosis and management-summary of NICE guidance". BMJ. 373: n1150. doi:10.1136/bmj.n1150. PMID 34020968 Check |pmid= value (help).
↑ López-López et al. https://doi.org/10.1136/bmj.j5058 . BMJ 2017
↑ Christopher B. Granger, M.D., John H. Alexander, M.D., M.H.S., John J.V. McMurray, M.D., Renato D. Lopes, M.D., Ph.D., Elaine M. Hylek, M.D., M.P.H., Michael Hanna, M.D., Hussein R. Al-Khalidi, Ph.D., Jack Ansell, M.D., Dan Atar, M.D., Alvaro Avezum, M.D., Ph.D., M. Cecilia Bahit, M.D., Rafael Diaz, M.D., J. Donald Easton, M.D., Justin A. Ezekowitz, M.B., B.Ch., Greg Flaker, M.D., David Garcia, M.D., Margarida Geraldes, Ph.D., Bernard J. Gersh, M.D., Sergey Golitsyn, M.D., Ph.D., Shinya Goto, M.D., Antonio G. Hermosillo, M.D., Stefan H. Hohnloser, M.D., John Horowitz, M.D., Puneet Mohan, M.D., Ph.D., Petr Jansky, M.D., Basil S. Lewis, M.D., Jose Luis Lopez-Sendon, M.D., Prem Pais, M.D., Alexander Parkhomenko, M.D., Freek W.A. Verheugt, M.D., Ph.D., Jun Zhu, M.D., and Lars Wallentin, M.D., Ph.D., for the ARISTOTLE Committees and Investigators* Apixaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2011; 365:981-992September 15, 2011DOI: 10.1056/NEJMoa1107039
↑ Stuart J. Connolly, M.D., Michael D. Ezekowitz, M.B., Ch.B., D.Phil., Salim Yusuf, F.R.C.P.C., D.Phil., John Eikelboom, M.D., Jonas Oldgren, M.D., Ph.D., Amit Parekh, M.D., Janice Pogue, M.Sc., Paul A. Reilly, Ph.D., Ellison Themeles, B.A., Jeanne Varrone, M.D., Susan Wang, Ph.D., Marco Alings, M.D., Ph.D., Denis Xavier, M.D., Jun Zhu, M.D., Rafael Diaz, M.D., Basil S. Lewis, M.D., Harald Darius, M.D., Hans-Christoph Diener, M.D., Ph.D., Campbell D. Joyner, M.D., Lars Wallentin, M.D., Ph.D., and *the RE-LY Steering Committee and Investigators. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. NEJM 2009; 361:1139-1151 September 17, 2009DOI: 10.1056/NEJMoa0905561
↑ Manesh R. Patel, M.D., Kenneth W. Mahaffey, M.D., Jyotsna Garg, M.S., Guohua Pan, Ph.D., Daniel E. Singer, M.D., Werner Hacke, M.D., Ph.D., Günter Breithardt, M.D., Jonathan L. Halperin, M.D., Graeme J. Hankey, M.D., Jonathan P. Piccini, M.D., Richard C. Becker, M.D., Christopher C. Nessel, M.D., John F. Paolini, M.D., Ph.D., Scott D. Berkowitz, M.D., Keith A.A. Fox, M.B., Ch.B., Robert M. Califf, M.D., and the ROCKET AF Steering Committee, for the ROCKET AF Investigators. Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med 2011; 365:883-891September 8, 2011DOI: 10.1056/NEJMoa1009638
↑ Robert P. Giugliano, M.D., Christian T. Ruff, M.D., M.P.H., Eugene Braunwald, M.D., Sabina A. Murphy, M.P.H., Stephen D. Wiviott, M.D., Jonathan L. Halperin, M.D., Albert L. Waldo, M.D., Michael D. Ezekowitz, M.D., D.Phil., Jeffrey I. Weitz, M.D., Jindřich Špinar, M.D., Witold Ruzyllo, M.D., Mikhail Ruda, M.D., Yukihiro Koretsune, M.D., Joshua Betcher, Ph.D., Minggao Shi, Ph.D., Laura T. Grip, A.B., Shirali P. Patel, B.S., Indravadan Patel, M.D., James J. Hanyok, Pharm.D., Michele Mercuri, M.D., and Elliott M. Antman, M.D., for the ENGAGE AF-TIMI 48 Investigators* Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2013; 369:2093-2104November 28, 2013DOI: 10.1056/NEJMoa1310907
↑ John W. Eikelboom, M.D., Stuart J. Connolly, M.D., Martina Brueckmann, M.D., Christopher B. Granger, M.D., Arie P. Kappetein, M.D., Ph.D., Michael J. Mack, M.D., Jon Blatchford, C.Stat., Kevin Devenny, B.Sc., Jeffrey Friedman, M.D., Kelly Guiver, M.Sc., Ruth Harper, Ph.D., Yasser Khder, M.D., Maximilian T. Lobmeyer, Ph.D., Hugo Maas, Ph.D., Jens-Uwe Voigt, M.D., Maarten L. Simoons, M.D., and Frans Van de Werf, M.D., Ph.D., for the RE-ALIGN Investigators. Dabigatran versus Warfarin in Patients with Mechanical Heart Valves. N Engl J Med 2013; 369:1206-1214September 26, 2013DOI: 10.1056/NEJMoa1300615
↑ ^12.0 ^12.1 ^12.2 Hart RG, Benavente O, McBride R, Pearce LA (1999). "Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis". Ann. Intern. Med. 131 (7): 492–501. Unknown parameter |month= ignored (help)
↑ Gorter JW (1999). "Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT). European Atrial Fibrillation Trial (EAFT) study groups". Neurology. 53 (6): 1319–27. PMID 10522891. Unknown parameter |month= ignored (help)
↑ Hylek EM, Singer DE (1994). "Risk factors for intracranial hemorrhage in outpatients taking warfarin". Ann. Intern. Med. 120 (11): 897–902. PMID 8172435. Unknown parameter |month= ignored (help)
↑ Hart RG, Halperin JL (1999). "Atrial fibrillation and thromboembolism: a decade of progress in stroke prevention". Ann. Intern. Med. 131 (9): 688–95. PMID 10577332. Unknown parameter |month= ignored (help)
↑ Hylek EM, Skates SJ, Sheehan MA, Singer DE (1996). "An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation". N. Engl. J. Med. 335 (8): 540–6. PMID 8678931. Unknown parameter |month= ignored (help)
↑ "Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial". Lancet. 348 (9028): 633–8. 1996. PMID 8782752. Unknown parameter |month= ignored (help)
↑ "Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. The European Atrial Fibrillation Trial Study Group". N. Engl. J. Med. 333 (1): 5–10. 1995. PMID 7776995. Unknown parameter |month= ignored (help)
↑ ^19.0 ^19.1 Hart RG (1998). "Intensity of anticoagulation to prevent stroke in patients with atrial fibrillation". Ann. Intern. Med. 128 (5): 408. PMID 9490603. Unknown parameter |month= ignored (help)
↑ "The efficacy of aspirin in patients with atrial fibrillation. Analysis of pooled data from 3 randomized trials. The Atrial Fibrillation Investigators". Arch. Intern. Med. 157 (11): 1237–40. 1997. PMID 9183235. Unknown parameter |month= ignored (help)
↑ Miller VT, Rothrock JF, Pearce LA, Feinberg WM, Hart RG, Anderson DC (1993). "Ischemic stroke in patients with atrial fibrillation: effect of aspirin according to stroke mechanism. Stroke Prevention in Atrial Fibrillation Investigators". Neurology. 43 (1): 32–6. PMID 8423907. Unknown parameter |month= ignored (help)
↑ Hart RG, Pearce LA, Miller VT; et al. (2000). "Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies". Cerebrovasc. Dis. 10 (1): 39–43. PMID 10629345.
↑ Flaker G et al. Bleeding During Treatment With Aspirin Versus Apixaban in Patients With Atrial Fibrillation Unsuitable for Warfarin: The Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin k Antagonist Treatment (AVERROES) Trial. Stroke 2012; 43: 3291-3297
↑ Chan KE, Lazarus JM, Thadhani R, Hakim RM. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol. 2009;20(10):2223.
↑ Wizemann V, Tong L, Satayathum S, Disney A, Akiba T, Fissell RB, Kerr PG, Young EW, Robinson BM. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int. 2010;77(12):1098.
↑ Winkelmayer WC, Liu J, Setoguchi S, Choudhry NK. Effectiveness and safety of warfarin initiation in older hemodialysis patients with incident atrial fibrillation. Clin J Am Soc Nephrol. 2011 Nov;6(11):2662-8. Epub 2011 Sep 29.
↑ Shah M, Avgil Tsadok M, Jackevicius CA, Essebag V, Eisenberg MJ, Rahme E, Humphries KH, Tu JV, Behlouli H, Guo H, Pilote L. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation. 2014;129(11):1196.
↑ Breithardt G, Baumgartner H, Berkowitz SD, Hellkamp AS, Piccini JP, Stevens SR, Lokhnygina Y, Patel MR, Halperin JL, Singer DE, Hankey GJ, Hacke W, Becker RC, Nessel CC, Mahaffey KW, Fox KA, Califf RM (December 2014). "Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial". Eur. Heart J. 35 (47): 3377–85. doi:10.1093/eurheartj/ehu305. PMC 4265383. PMID 25148838.
↑ Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML, Van de Werf F (September 2013). "Dabigatran versus warfarin in patients with mechanical heart valves". N. Engl. J. Med. 369 (13): 1206–14. doi:10.1056/NEJMoa1300615. PMID 23991661.
↑ Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (November 2016). "2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS". Eur J Cardiothorac Surg. 50 (5): e1–e88. doi:10.1093/ejcts/ezw313. PMID 27663299.
↑ Tsai YC, Phan K, Munkholm-Larsen S, Tian DH, La Meir M, Yan TD (May 2015). "Surgical left atrial appendage occlusion during cardiac surgery for patients with atrial fibrillation: a meta-analysis". Eur J Cardiothorac Surg. 47 (5): 847–54. doi:10.1093/ejcts/ezu291. PMID 25064051.
↑ Wann, LS.; Curtis, AB.; January, CT.; Ellenbogen, KA.; Lowe, JE.; Estes, NA.; Page, RL.; Ezekowitz, MD.; Slotwiner, DJ. (2011). "2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Heart Rhythm. 8 (1): 157–76. doi:10.1016/j.hrthm.2010.11.047. PMID 21182985. Unknown parameter |month= ignored (help)
↑ ^33.0 ^33.1 Abraham NS, Hlatky MA, Antman EM, Bhatt DL, Bjorkman DJ, Clark CB; et al. (2010). "ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents". Circulation. 122 (24): 2619–33. doi:10.1161/CIR.0b013e318202f701. PMID 21060077.
↑ Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2011) 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 123 (10):e269-367. DOI:10.1161/CIR.0b013e318214876d PMID: 21382897
↑ Estes NA, Halperin JL, Calkins H, Ezekowitz MD, Gitman P, Go AS et al. (2008) ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (Writing Committee to Develop Clinical Performance Measures for Atrial Fibrillation): developed in collaboration with the Heart Rhythm Society. Circulation 117 (8):1101-20. DOI:10.1161/CIRCULATIONAHA.107.187192 PMID: 18283199
↑ Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2006) ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 114 (7):e257-354. DOI:10.1161/CIRCULATIONAHA.106.177292 PMID: 16908781

Template:WikiDoc Sources CME Category::Cardiology

[1] Van Gelder, Isabelle C.; Rienstra, Michiel; Bunting, Karina V.; Casado-Arroyo, Ruben; Caso, Valeria; Crijns, Harry J G M; De Potter, Tom J R; Dwight, Jeremy; Guasti, Luigina; Hanke, Thorsten; Jaarsma, Tiny; Lettino, Maddalena; Løchen, Maja-Lisa; Lumbers, R Thomas; Maesen, Bart; Mølgaard, Inge; Rosano, Giuseppe M C; Sanders, Prashanthan; Schnabel, Renate B; Suwalski, Piotr; Svennberg, Emma; Tamargo, Juan; Tica, Otilia; Traykov, Vassil; Tzeis, Stylianos; Kotecha, Dipak (2024). "2024 ESC Guidelines for the Management of Atrial Fibrillation". European Heart Journal. 45 (36): 3314–3403. doi:10.1093/eurheartj/ehaa612

[pmid27637120-2] Gutierrez C, Blanchard DG (2016). "Diagnosis and Treatment of Atrial Fibrillation". Am Fam Physician. 94 (6): 442–52. PMID 27637120.

[pmid29562325-3] Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L; et al. (2018). "The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation". Eur Heart J. 39 (16): 1330–1393. doi:10.1093/eurheartj/ehy136. PMID 29562325.

[JanuaryWann2014-4] 4.0 ^4.1 ^4.2 January, C. T.; Wann, L. S.; Alpert, J. S.; Calkins, H.; Cleveland, J. C.; Cigarroa, J. E.; Conti, J. B.; Ellinor, P. T.; Ezekowitz, M. D.; Field, M. E.; Murray, K. T.; Sacco, R. L.; Stevenson, W. G.; Tchou, P. J.; Tracy, C. M.; Yancy, C. W. (2014). "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 Practice Guidelines and the Heart Rhythm Society". Circulation. doi:10.1161/CIR.0000000000000041. ISSN 0009-7322.

[pmid34020968-5] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 ^5.6 ^5.7 Perry M, Kemmis Betty S, Downes N, Andrews N, Mackenzie S, Guideline Committee (2021). "Atrial fibrillation: diagnosis and management-summary of NICE guidance". BMJ. 373: n1150. doi:10.1136/bmj.n1150. PMID 34020968 Check |pmid= value (help).

[6] López-López et al. https://doi.org/10.1136/bmj.j5058 . BMJ 2017

[7] Christopher B. Granger, M.D., John H. Alexander, M.D., M.H.S., John J.V. McMurray, M.D., Renato D. Lopes, M.D., Ph.D., Elaine M. Hylek, M.D., M.P.H., Michael Hanna, M.D., Hussein R. Al-Khalidi, Ph.D., Jack Ansell, M.D., Dan Atar, M.D., Alvaro Avezum, M.D., Ph.D., M. Cecilia Bahit, M.D., Rafael Diaz, M.D., J. Donald Easton, M.D., Justin A. Ezekowitz, M.B., B.Ch., Greg Flaker, M.D., David Garcia, M.D., Margarida Geraldes, Ph.D., Bernard J. Gersh, M.D., Sergey Golitsyn, M.D., Ph.D., Shinya Goto, M.D., Antonio G. Hermosillo, M.D., Stefan H. Hohnloser, M.D., John Horowitz, M.D., Puneet Mohan, M.D., Ph.D., Petr Jansky, M.D., Basil S. Lewis, M.D., Jose Luis Lopez-Sendon, M.D., Prem Pais, M.D., Alexander Parkhomenko, M.D., Freek W.A. Verheugt, M.D., Ph.D., Jun Zhu, M.D., and Lars Wallentin, M.D., Ph.D., for the ARISTOTLE Committees and Investigators* Apixaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2011; 365:981-992September 15, 2011DOI: 10.1056/NEJMoa1107039

[8] Stuart J. Connolly, M.D., Michael D. Ezekowitz, M.B., Ch.B., D.Phil., Salim Yusuf, F.R.C.P.C., D.Phil., John Eikelboom, M.D., Jonas Oldgren, M.D., Ph.D., Amit Parekh, M.D., Janice Pogue, M.Sc., Paul A. Reilly, Ph.D., Ellison Themeles, B.A., Jeanne Varrone, M.D., Susan Wang, Ph.D., Marco Alings, M.D., Ph.D., Denis Xavier, M.D., Jun Zhu, M.D., Rafael Diaz, M.D., Basil S. Lewis, M.D., Harald Darius, M.D., Hans-Christoph Diener, M.D., Ph.D., Campbell D. Joyner, M.D., Lars Wallentin, M.D., Ph.D., and *the RE-LY Steering Committee and Investigators. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. NEJM 2009; 361:1139-1151 September 17, 2009DOI: 10.1056/NEJMoa0905561

[9] Manesh R. Patel, M.D., Kenneth W. Mahaffey, M.D., Jyotsna Garg, M.S., Guohua Pan, Ph.D., Daniel E. Singer, M.D., Werner Hacke, M.D., Ph.D., Günter Breithardt, M.D., Jonathan L. Halperin, M.D., Graeme J. Hankey, M.D., Jonathan P. Piccini, M.D., Richard C. Becker, M.D., Christopher C. Nessel, M.D., John F. Paolini, M.D., Ph.D., Scott D. Berkowitz, M.D., Keith A.A. Fox, M.B., Ch.B., Robert M. Califf, M.D., and the ROCKET AF Steering Committee, for the ROCKET AF Investigators. Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med 2011; 365:883-891September 8, 2011DOI: 10.1056/NEJMoa1009638

[10] Robert P. Giugliano, M.D., Christian T. Ruff, M.D., M.P.H., Eugene Braunwald, M.D., Sabina A. Murphy, M.P.H., Stephen D. Wiviott, M.D., Jonathan L. Halperin, M.D., Albert L. Waldo, M.D., Michael D. Ezekowitz, M.D., D.Phil., Jeffrey I. Weitz, M.D., Jindřich Špinar, M.D., Witold Ruzyllo, M.D., Mikhail Ruda, M.D., Yukihiro Koretsune, M.D., Joshua Betcher, Ph.D., Minggao Shi, Ph.D., Laura T. Grip, A.B., Shirali P. Patel, B.S., Indravadan Patel, M.D., James J. Hanyok, Pharm.D., Michele Mercuri, M.D., and Elliott M. Antman, M.D., for the ENGAGE AF-TIMI 48 Investigators* Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2013; 369:2093-2104November 28, 2013DOI: 10.1056/NEJMoa1310907

[11] John W. Eikelboom, M.D., Stuart J. Connolly, M.D., Martina Brueckmann, M.D., Christopher B. Granger, M.D., Arie P. Kappetein, M.D., Ph.D., Michael J. Mack, M.D., Jon Blatchford, C.Stat., Kevin Devenny, B.Sc., Jeffrey Friedman, M.D., Kelly Guiver, M.Sc., Ruth Harper, Ph.D., Yasser Khder, M.D., Maximilian T. Lobmeyer, Ph.D., Hugo Maas, Ph.D., Jens-Uwe Voigt, M.D., Maarten L. Simoons, M.D., and Frans Van de Werf, M.D., Ph.D., for the RE-ALIGN Investigators. Dabigatran versus Warfarin in Patients with Mechanical Heart Valves. N Engl J Med 2013; 369:1206-1214September 26, 2013DOI: 10.1056/NEJMoa1300615

[pmid-12] 12.0 ^12.1 ^12.2 Hart RG, Benavente O, McBride R, Pearce LA (1999). "Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis". Ann. Intern. Med. 131 (7): 492–501. Unknown parameter |month= ignored (help)

[pmid10522891-13] Gorter JW (1999). "Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT). European Atrial Fibrillation Trial (EAFT) study groups". Neurology. 53 (6): 1319–27. PMID 10522891. Unknown parameter |month= ignored (help)

[pmid8172435-14] Hylek EM, Singer DE (1994). "Risk factors for intracranial hemorrhage in outpatients taking warfarin". Ann. Intern. Med. 120 (11): 897–902. PMID 8172435. Unknown parameter |month= ignored (help)

[pmid10577332-15] Hart RG, Halperin JL (1999). "Atrial fibrillation and thromboembolism: a decade of progress in stroke prevention". Ann. Intern. Med. 131 (9): 688–95. PMID 10577332. Unknown parameter |month= ignored (help)

[pmid8678931-16] Hylek EM, Skates SJ, Sheehan MA, Singer DE (1996). "An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation". N. Engl. J. Med. 335 (8): 540–6. PMID 8678931. Unknown parameter |month= ignored (help)

[pmid8782752-17] "Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial". Lancet. 348 (9028): 633–8. 1996. PMID 8782752. Unknown parameter |month= ignored (help)

[pmid7776995-18] "Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. The European Atrial Fibrillation Trial Study Group". N. Engl. J. Med. 333 (1): 5–10. 1995. PMID 7776995. Unknown parameter |month= ignored (help)

[pmid9490603-19] 19.0 ^19.1 Hart RG (1998). "Intensity of anticoagulation to prevent stroke in patients with atrial fibrillation". Ann. Intern. Med. 128 (5): 408. PMID 9490603. Unknown parameter |month= ignored (help)

[pmid9183235-20] "The efficacy of aspirin in patients with atrial fibrillation. Analysis of pooled data from 3 randomized trials. The Atrial Fibrillation Investigators". Arch. Intern. Med. 157 (11): 1237–40. 1997. PMID 9183235. Unknown parameter |month= ignored (help)

[pmid8423907-21] Miller VT, Rothrock JF, Pearce LA, Feinberg WM, Hart RG, Anderson DC (1993). "Ischemic stroke in patients with atrial fibrillation: effect of aspirin according to stroke mechanism. Stroke Prevention in Atrial Fibrillation Investigators". Neurology. 43 (1): 32–6. PMID 8423907. Unknown parameter |month= ignored (help)

[pmid10629345-22] Hart RG, Pearce LA, Miller VT; et al. (2000). "Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies". Cerebrovasc. Dis. 10 (1): 39–43. PMID 10629345.

[23] Flaker G et al. Bleeding During Treatment With Aspirin Versus Apixaban in Patients With Atrial Fibrillation Unsuitable for Warfarin: The Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin k Antagonist Treatment (AVERROES) Trial. Stroke 2012; 43: 3291-3297

[24] Chan KE, Lazarus JM, Thadhani R, Hakim RM. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol. 2009;20(10):2223.

[25] Wizemann V, Tong L, Satayathum S, Disney A, Akiba T, Fissell RB, Kerr PG, Young EW, Robinson BM. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int. 2010;77(12):1098.

[26] Winkelmayer WC, Liu J, Setoguchi S, Choudhry NK. Effectiveness and safety of warfarin initiation in older hemodialysis patients with incident atrial fibrillation. Clin J Am Soc Nephrol. 2011 Nov;6(11):2662-8. Epub 2011 Sep 29.

[27] Shah M, Avgil Tsadok M, Jackevicius CA, Essebag V, Eisenberg MJ, Rahme E, Humphries KH, Tu JV, Behlouli H, Guo H, Pilote L. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation. 2014;129(11):1196.

[pmid25148838-28] Breithardt G, Baumgartner H, Berkowitz SD, Hellkamp AS, Piccini JP, Stevens SR, Lokhnygina Y, Patel MR, Halperin JL, Singer DE, Hankey GJ, Hacke W, Becker RC, Nessel CC, Mahaffey KW, Fox KA, Califf RM (December 2014). "Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial". Eur. Heart J. 35 (47): 3377–85. doi:10.1093/eurheartj/ehu305. PMC 4265383. PMID 25148838.

[pmid23991661-29] Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML, Van de Werf F (September 2013). "Dabigatran versus warfarin in patients with mechanical heart valves". N. Engl. J. Med. 369 (13): 1206–14. doi:10.1056/NEJMoa1300615. PMID 23991661.

[pmid27663299-30] Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (November 2016). "2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS". Eur J Cardiothorac Surg. 50 (5): e1–e88. doi:10.1093/ejcts/ezw313. PMID 27663299.

[pmid25064051-31] Tsai YC, Phan K, Munkholm-Larsen S, Tian DH, La Meir M, Yan TD (May 2015). "Surgical left atrial appendage occlusion during cardiac surgery for patients with atrial fibrillation: a meta-analysis". Eur J Cardiothorac Surg. 47 (5): 847–54. doi:10.1093/ejcts/ezu291. PMID 25064051.

[Wann-2011-32] Wann, LS.; Curtis, AB.; January, CT.; Ellenbogen, KA.; Lowe, JE.; Estes, NA.; Page, RL.; Ezekowitz, MD.; Slotwiner, DJ. (2011). "2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Heart Rhythm. 8 (1): 157–76. doi:10.1016/j.hrthm.2010.11.047. PMID 21182985. Unknown parameter |month= ignored (help)

[pmid21060077-33] 33.0 ^33.1 Abraham NS, Hlatky MA, Antman EM, Bhatt DL, Bjorkman DJ, Clark CB; et al. (2010). "ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents". Circulation. 122 (24): 2619–33. doi:10.1161/CIR.0b013e318202f701. PMID 21060077.

[pmid21382897-34] Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2011) 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 123 (10):e269-367. DOI:10.1161/CIR.0b013e318214876d PMID: 21382897

[pmid18283199-35] Estes NA, Halperin JL, Calkins H, Ezekowitz MD, Gitman P, Go AS et al. (2008) ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (Writing Committee to Develop Clinical Performance Measures for Atrial Fibrillation): developed in collaboration with the Heart Rhythm Society. Circulation 117 (8):1101-20. DOI:10.1161/CIRCULATIONAHA.107.187192 PMID: 18283199

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v t e Electrocardiography
Overview	History of the EKG • EKG interpretation basics • Normal sinus rhythm
EKG Complexes	P wave • QRS complex • ST Segment • T wave • T wave alternans • Tombstone T wave • U wave Osborn wave • H wave • K wave • Delta wave NSSTW changes
EKG Intervals	PR Interval • QRS Interval • ST Interval • QT Interval
Conduction System & Bradycardia	Cardiac pacemaker • SA node • AV node• Bundle of His • Purkinje fibers • Sinus bradycardia • First Degree AV Block • Second Degree AV Block • Complete or Third-Degree AV Block • Concealed conduction • AV Junctional Rhythms • LBBB • LAHB • LPHB • RBBB • Trifascicular block
Atrial Arrhythmias	Sinus tachycardia • Premature Atrial Contractions (PACs) • Ectopic Atrial Rhythm • Paroxysmal Atrial Tachycardia (PAT) • Paroxysmal Atrial Tachycardia (PAT) with Block • Multifocal Atrial Tachycardia (MAT) • Atrial Flutter • Atrial Fibrillation • Wandering atrial pacemaker
Ventricular Arrhythmias	Differential Diagnosis of Tachycardia with a Wide QRS Complex • Accelerated Idioventricular Rhythm • Ventricular Parasystole • Premature Ventricular Contractions (PVCs) • Ventricular tachycardia • Ventricular Fibrillation • Sudden cardiac death
EKG Abnormalities in Disease States	Hypertrophy & Dilatation • Right atrial enlargement • Left atrial enlargement • Biatrial enlargement • Left Ventricular Hypertrophy • Right Ventricular Hypertrophy • Biventricular Hypertrophy • Acute myocardial infarction • NSTEMI • STEMI • Tombstone ST elevation • Right ventricular myocardial infarction • Atrial infarction Pre-excitation Syndromes • Wolff-Parkinson-White Syndrome • Lown Ganong Levine Syndrome • Mahaim Type Preexcitation Cardiomyopathies • Arrhythmogenic Right Ventricular Dysplasia • Dilated Cardiomyopathy • Hypertrophic Cardiomyopathy Drug Effects on the EKG • Adenosine • β-blockers • Digitalis • Quinidine • Procainamide • Disopyramide • Lidocaine • Tocainide and Mexiletine • Phenytoin • Encainide, Flecainide and Propafenone • Amiodarone • Bretylium • Ca Channel Blockers • Phenothiazines • Tricyclic Antidepressants • Lithium Congenital Heart Disease • Dextrocardia • Atrial Septal Defect • Ventricular Septal Defect • Tetralogy of Fallot • Conjoined Twins or Siamese Twins • Congenital heart block Electrolyte Disturbances • Hyperkalemia • Hypokalemia • Hypercalcemia • Hypocalcemia • Nonspecific Changes Other Heart Diseases • Pericarditis • Myocarditis • Tamponade • Heart Transplantation • Sick Sinus Syndrome • Long QT Syndrome Inherited Disease • Brugada Syndrome Systemic Diseases • CNS Disease • Cardiac Tumors Heart Transplantation • EKG Changes in patient with Heart Transplantation Exogenous Effects • Hypothermia • Chest Trauma • Insect Bites • Electric Injuries
Technical Issues and Potential Errors in Interpretation	Artifacts • Lead Placement Errors • The EKG in a Patient with a Pacemaker • EKG in athletes


Atrial Fibrillation Microchapters
Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Atrial Fibrillation from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Special Groups Postoperative AF Acute Myocardial Infarction Wolff-Parkinson-White Preexcitation Syndrome Hypertrophic Cardiomyopathy Hyperthyroidism Pulmonary Diseases Pregnancy ACS and/or PCI or valve intervention Heart failure

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram EKG Examples A-Fib with LBBB

Chest X Ray

Echocardiography

Holter Monitoring and Exercise Stress Testing

Cardiac MRI

Treatment

Rate and Rhythm Control

Cardioversion Overview Electrical Cardioversion Pharmacological Cardioversion

Anticoagulation Overview Warfarin Converting from or to Warfarin Converting from or to Parenteral Anticoagulants Dabigatran

Maintenance of Sinus Rhythm

Surgery Catheter Ablation AV Nodal Ablation Surgical Ablation Cardiac Surgery
Specific Patient Groups

Primary Prevention
Secondary Prevention

Supportive Trial Data

Cost-Effectiveness of Therapy

Case Studies

Case #1

Atrial fibrillation anticoagulation On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Atrial fibrillation anticoagulation

CDC on Atrial fibrillation anticoagulation

Atrial fibrillation anticoagulation in the news

Blogs on Atrial fibrillation anticoagulation

Directions to Hospitals Treating Atrial fibrillation anticoagulation

Risk calculators and risk factors for Atrial fibrillation anticoagulation

Atrial fibrillation anticoagulation

Overview

Atrial fibrillation anticoagulation

CHADS2-VASc score For more information regards CHA2DS2-VASc Score click here

Anticoagulation Treatment Summary for Acute Atrial Fibrillation - NICE Guideline

Anticoagulation Options

Novel Oral Anticoagulants

Warfarin

Antiplatelet Therapy for Atrial Fibrillation (not recommended)

Aspirin Monotherapy

Dual Antiplatelet Therapy

Anticoagulation in end stage renal disease

Anticoagulation Reassessment

Interruption of Anticoagulation

2019 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline

2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease (VHD)

Recommendation for Anticoagulation for Atrial Fibrillation (AF) in Patients with VHD

2017 ESC/EACTS Guidelines for the Management of Atrial Fibrillation in Patients With Valvular Heart Disease (VHD)

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (DO NOT EDIT)[4]

Prevention of Thromboembolism

Risk-Based Antithrombotic Therapy

2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline) (DO NOT EDIT)[32]

Combining Anticoagulant with Antiplatelet Therapy

2010 ACCF/ACG/AHA Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines - Summary of Findings and Consensus Recommendations[33] (DO NOT EDIT)

Sources

References

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2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (DO NOT EDIT)^[4]

2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline) (DO NOT EDIT)^[32]

2010 ACCF/ACG/AHA Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines - Summary of Findings and Consensus Recommendations^[33] (DO NOT EDIT)