Atrial fibrillation anticoagulation: Difference between revisions

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===Oral Anticoagulation (Coumadin) versus Dual Antiplatelet Therapy (ASA/Clopidogrel)===
===Oral Anticoagulation (Coumadin) versus Dual Antiplatelet Therapy (ASA/Clopidogrel)===
In the ACTIVE W trial, dual antiplatelet therapy with [[aspirin]] (75-100 mg per day) and [[clopidogrel]] (75 mg per day) was found to be statistically inferior to [[coumadin]] therapy (target INR 2.0 to 3.0) in the management of patients with [[atrial fibrillation]] who had one or more risk factors for [[stroke]].<ref> The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Lancet 2006;367:1903-12.</ref>  The primary endpoint of ACTIVE W was the first occurrence of [[stroke]], non-CNS systemic embolus, [[myocardial infarction]], or vascular death.  The annual risk in the coumadin group was 3.93% per year, and in the [[aspirin]]/[[clopidogrel]] group it was 5.60% per year yielding a relative risk of 1.44 (1.18-1.76; p=0.0003).  The efficacy was not as great among patients who were coumadin naive, although the p-value for the interaction was negative.  There was no excess bleeding among patients treated with coumadin, and in fact there was an excess of minor bleeds among patients treated with [[ASA]] and [[clopidogrel]] (13.6% / yr vs 11.5% year, p=0.0009).  
In the ACTIVE W trial, dual antiplatelet therapy with [[aspirin]] (75-100 mg per day) and [[clopidogrel]] (75 mg per day) was found to be statistically inferior to [[coumadin]] therapy (target INR 2.0 to 3.0) in the management of patients with [[atrial fibrillation]] who had one or more risk factors for [[stroke]].<ref>The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Lancet 2006;367:1903-12.</ref>  The primary endpoint of ACTIVE W was the first occurrence of [[stroke]], non-CNS systemic embolus, [[myocardial infarction]], or vascular death.  The annual risk in the coumadin group was 3.93% per year, and in the [[aspirin]]/[[clopidogrel]] group it was 5.60% per year yielding a relative risk of 1.44 (1.18-1.76; p=0.0003).  The efficacy was not as great among patients who were coumadin naive, although the p-value for the interaction was negative.  There was no excess bleeding among patients treated with coumadin, and in fact there was an excess of minor bleeds among patients treated with [[ASA]] and [[clopidogrel]] (13.6% / yr vs 11.5% year, p=0.0009).  


When examining the data from atrial fibrillation trials, it is critical to evaluate the results in patients who were previously treated with [[coumadin]] separate from those patients who were naive to coumadin.  Patients previously treated with coumadin are likely to be those patients who  best tolerate coumadin and have passed their bleeding stress test and have a lower rate of bleeding on coumadin.  Those patients who bleed while on [[coumadin]] have already been culled out from the population.  When the data in ACTIVE W were evaluated including only those patients previously treated with [[coumadin]] (again  a population to be anticipated to be at low risk of bleeding), the risk of major bleeding was indeed statistically significantly lower among patients previously treated with coumadin (p=0.03) than patients not previously treated.
When examining the data from atrial fibrillation trials, it is critical to evaluate the results in patients who were previously treated with [[coumadin]] separate from those patients who were naive to coumadin.  Patients previously treated with coumadin are likely to be those patients who  best tolerate coumadin and have passed their bleeding stress test and have a lower rate of bleeding on coumadin.  Those patients who bleed while on [[coumadin]] have already been culled out from the population.  When the data in ACTIVE W were evaluated including only those patients previously treated with [[coumadin]] (again  a population to be anticipated to be at low risk of bleeding), the risk of major bleeding was indeed statistically significantly lower among patients previously treated with coumadin (p=0.03) than patients not previously treated.
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The majority of the reduction in events was due to a reduction in [[stroke]] and non CNS embolization associated with coumadin therapy.  The pathophysiology of stroke among patients with atrial fibrillation is thought to be embolization from clot in the [[left atrium]].  The data from ACTIVE W suggest that platelet activation and its treatment may not play a pivotal role in the treatment of mural thrombus and embolization in atrial fibrillation.  Coumadin was more effective in the reduction of non disabling [[stroke]] rather than disabling stroke.  There were more fatal hemorrhagic strokes (which may more often be  fatal), and this may explain in part why coumadin was not associated  with a reduction in mortality in the study.
The majority of the reduction in events was due to a reduction in [[stroke]] and non CNS embolization associated with coumadin therapy.  The pathophysiology of stroke among patients with atrial fibrillation is thought to be embolization from clot in the [[left atrium]].  The data from ACTIVE W suggest that platelet activation and its treatment may not play a pivotal role in the treatment of mural thrombus and embolization in atrial fibrillation.  Coumadin was more effective in the reduction of non disabling [[stroke]] rather than disabling stroke.  There were more fatal hemorrhagic strokes (which may more often be  fatal), and this may explain in part why coumadin was not associated  with a reduction in mortality in the study.


While clopidogrel plus aspirin has been found to reduce the risk of recurrent [[myocardial infarction]] among patients with presumed plaque rupture and [[acute coronary syndromes]], it is notable in ACTIVE W that the risk of [[myocardial infarction]] tended to be higher among patients treated with [[aspirin]] plus [[clopidogrel]] versus [[coumadin]] (0.86% vs 0.55%,p=0.09).<ref> The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Lancet 2006;367:1903-12.</ref>
While clopidogrel plus aspirin has been found to reduce the risk of recurrent [[myocardial infarction]] among patients with presumed plaque rupture and [[acute coronary syndromes]], it is notable in ACTIVE W that the risk of [[myocardial infarction]] tended to be higher among patients treated with [[aspirin]] plus [[clopidogrel]] versus [[coumadin]] (0.86% vs 0.55%,p=0.09).<ref>The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Lancet 2006;367:1903-12.</ref>
 
=== '''Anticoagulation in end stage renal disease''' ===
Patients with end stage renal disease were excluded from the trials of warfarin in AF, as well as from the trials of the NOACs in AF.  There is no high quality randomized data looking at anticoagulation in patients with AF and ESRD.  Given the risk factors for kidney disease, most patients with AF and ESRD 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 ESRD given a markedly increased risk for intracranial bleeding <ref>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.</ref><ref><br>
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.</ref><ref>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.</ref><ref><br>
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.</ref>.  This may be related to baseline bleeding propensity in ESRD from uremic platelet dysfunction as well as issues with maintaining a therapeutic INR.  Use of warfarin in ESRD 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 LV 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.


==2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (DO NOT EDIT)<ref name="JanuaryWann2014">{{cite journal|last1=January|first1=C. T.|last2=Wann|first2=L. S.|last3=Alpert|first3=J. S.|last4=Calkins|first4=H.|last5=Cleveland|first5=J. C.|last6=Cigarroa|first6=J. E.|last7=Conti|first7=J. B.|last8=Ellinor|first8=P. T.|last9=Ezekowitz|first9=M. D.|last10=Field|first10=M. E.|last11=Murray|first11=K. T.|last12=Sacco|first12=R. L.|last13=Stevenson|first13=W. G.|last14=Tchou|first14=P. J.|last15=Tracy|first15=C. M.|last16=Yancy|first16=C. W.|title=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|journal=Circulation|year=2014|issn=0009-7322|doi=10.1161/CIR.0000000000000041}}</ref>==
==2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (DO NOT EDIT)<ref name="JanuaryWann2014">{{cite journal|last1=January|first1=C. T.|last2=Wann|first2=L. S.|last3=Alpert|first3=J. S.|last4=Calkins|first4=H.|last5=Cleveland|first5=J. C.|last6=Cigarroa|first6=J. E.|last7=Conti|first7=J. B.|last8=Ellinor|first8=P. T.|last9=Ezekowitz|first9=M. D.|last10=Field|first10=M. E.|last11=Murray|first11=K. T.|last12=Sacco|first12=R. L.|last13=Stevenson|first13=W. G.|last14=Tchou|first14=P. J.|last15=Tracy|first15=C. M.|last16=Yancy|first16=C. W.|title=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|journal=Circulation|year=2014|issn=0009-7322|doi=10.1161/CIR.0000000000000041}}</ref>==
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{{Seealso|CHA2DS2-VASc Score}}
{{Seealso|CHA2DS2-VASc Score}}


{|class="wikitable" style="width: 80%;"
{| class="wikitable" style="width: 80%;"
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In patients with [[AF]], [[antithrombotic therapy]] should be individualized based on shared decision-making after discussion of the absolute and [[relative risk|RRs]] of [[stroke]] and [[bleeding]], and the patient’s values and preferences. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' In patients with [[AF]], [[antithrombotic therapy]] should be individualized based on shared decision-making after discussion of the absolute and [[relative risk|RRs]] of [[stroke]] and [[bleeding]], and the patient’s values and preferences. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Selection of [[antithrombotic therapy]] should be based on the risk of [[thromboembolism]] irrespective of whether the [[AF]] pattern is paroxysmal, persistent, or permanent. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''2.''' Selection of [[antithrombotic therapy]] should be based on the risk of [[thromboembolism]] irrespective of whether the [[AF]] pattern is paroxysmal, persistent, or permanent. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' In patients with nonvalvular [[AF]], the [[CHA2DS2-VASc score]] is recommended for assessment of stroke risk. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''3.''' In patients with nonvalvular [[AF]], the [[CHA2DS2-VASc score]] is recommended for assessment of stroke risk. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' For patients with [[AF]] who have [[mechanical heart valve]]s, [[warfarin]] is recommended and the target [[INR|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]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''4.''' For patients with [[AF]] who have [[mechanical heart valve]]s, [[warfarin]] is recommended and the target [[INR|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]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' For patients with nonvalvular [[AF]] with prior [[stroke]], [[TIA|transient ischemic attack (TIA)]], or a [[CHA2DS2-VASc score]] of 2 or greater, oral [[anticoagulant]]s are recommended. Options include: [[warfarin]] ([[INR]] 2.0 to 3.0) ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'', [[dabigatran]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'', [[rivaroxaban]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'', or [[apixaban]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''.<nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''5.''' For patients with nonvalvular [[AF]] with prior [[stroke]], [[TIA|transient ischemic attack (TIA)]], or a [[CHA2DS2-VASc score]] of 2 or greater, oral [[anticoagulant]]s are recommended. Options include: [[warfarin]] ([[INR]] 2.0 to 3.0) ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'', [[dabigatran]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'', [[rivaroxaban]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'', or [[apixaban]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''.<nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''7.''' For patients with nonvalvular [[AF]] unable to maintain a therapeutic [[INR]] level with [[warfarin]], use of a [[DTI|direct thrombin]] or [[Direct Xa inhibitor|factor Xa inhibitor]] ([[dabigatran]], [[rivaroxaban]], or [[apixaban]]) is recommended. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''7.''' For patients with nonvalvular [[AF]] unable to maintain a therapeutic [[INR]] level with [[warfarin]], use of a [[DTI|direct thrombin]] or [[Direct Xa inhibitor|factor Xa inhibitor]] ([[dabigatran]], [[rivaroxaban]], or [[apixaban]]) is recommended. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''8.''' Re-evaluation of the need for and choice of [[antithrombotic therapy]] at periodic intervals is recommended to reassess [[stroke]] and [[bleeding]] risks. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''8.''' Re-evaluation of the need for and choice of [[antithrombotic therapy]] at periodic intervals is recommended to reassess [[stroke]] and [[bleeding]] risks. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''9.''' Bridging therapy with [[UFH|unfractionated heparin (UFH)]] or [[LMWH|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]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''9.''' Bridging therapy with [[UFH|unfractionated heparin (UFH)]] or [[LMWH|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]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''10.''' For patients with [[AF]] without [[mechanical heart valve]]s who require interruption of [[warfarin]] or newer [[anticoagulant]]s 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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''10.''' For patients with [[AF]] without [[mechanical heart valve]]s who require interruption of [[warfarin]] or newer [[anticoagulant]]s 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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''11.''' [[Renal function]] should be evaluated prior to initiation of [[DTI|direct thrombin]] or [[Direct Xa inhibitor|factor Xa inhibitors]] and should be re-evaluated when clinically indicated and at least annually. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''11.''' [[Renal function]] should be evaluated prior to initiation of [[DTI|direct thrombin]] or [[Direct Xa inhibitor|factor Xa inhibitors]] and should be re-evaluated when clinically indicated and at least annually. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''12.''' For patients with [[atrial flutter]], [[antithrombotic therapy]] is recommended according to the same risk profile used for [[AF]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''12.''' For patients with [[atrial flutter]], [[antithrombotic therapy]] is recommended according to the same risk profile used for [[AF]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|}  
|}  


{|class="wikitable" style="width: 80%;"
{| class="wikitable" style="width: 80%;"
|-
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III: No Benefit]]
| colspan="1" style="text-align:center; background:LightCoral" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III: No Benefit]]
|-
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' The [[DTI|direct thrombin inhibitor]], [[dabigatran]], and the [[Direct Xa inhibitor|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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LightCoral" |<nowiki>"</nowiki>'''1.''' The [[DTI|direct thrombin inhibitor]], [[dabigatran]], and the [[Direct Xa inhibitor|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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|}
|}


{|class="wikitable" style="width: 80%;"
{| class="wikitable" style="width: 80%;"
|-
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III: Harm]]
| colspan="1" style="text-align:center; background:LightCoral" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III: Harm]]
|-
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' The [[DTI|direct thrombin inhibitor]], [[dabigatran]], should not be used in patients with [[AF]] and a [[mechanical heart valve]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LightCoral" |<nowiki>"</nowiki>'''1.''' The [[DTI|direct thrombin inhibitor]], [[dabigatran]], should not be used in patients with [[AF]] and a [[mechanical heart valve]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}
|}


{|class="wikitable" style="width: 80%;"
{| class="wikitable" style="width: 80%;"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' For patients with nonvalvular [[AF]] and a [[CHA2DS2-VASc score]] of 0, it is reasonable to omit [[antithrombotic therapy]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' For patients with nonvalvular [[AF]] and a [[CHA2DS2-VASc score]] of 0, it is reasonable to omit [[antithrombotic therapy]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' For patients with nonvalvular [[AF]] with a [[CHA2DS2-VASc score]] of 2 or greater and who have end-stage [[CKD]] ([[creatinine clearance|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]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''2.''' For patients with nonvalvular [[AF]] with a [[CHA2DS2-VASc score]] of 2 or greater and who have end-stage [[CKD]] ([[creatinine clearance|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]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}
|}


{|class="wikitable" style="width: 80%;"
{| class="wikitable" style="width: 80%;"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' For patients with nonvalvular [[AF]] and moderate-to-severe [[CKD]] with [[CHA2DS2-VASc score]]s of 2 or greater, treatment with reduced doses of [[DTI|direct thrombin]] or [[Direct Xa inhibitor|factor Xa inhibitors]] may be considered (e.g., [[dabigatran]], [[rivaroxaban]], or [[apixaban]]), but safety and efficacy have not been established. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''2.''' For patients with nonvalvular [[AF]] and moderate-to-severe [[CKD]] with [[CHA2DS2-VASc score]]s of 2 or greater, treatment with reduced doses of [[DTI|direct thrombin]] or [[Direct Xa inhibitor|factor Xa inhibitors]] may be considered (e.g., [[dabigatran]], [[rivaroxaban]], or [[apixaban]]), but safety and efficacy have not been established. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' In patients with [[AF]] undergoing [[percutaneous coronary intervention]], [[bare-metal stent]]s 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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''3.''' In patients with [[AF]] undergoing [[percutaneous coronary intervention]], [[bare-metal stent]]s 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. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''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 [[anticoagulant]]s but without [[aspirin]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''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 [[anticoagulant]]s but without [[aspirin]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}
|}


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===Combining Anticoagulant with Antiplatelet Therapy===
===Combining Anticoagulant with Antiplatelet Therapy===


{|class="wikitable" style="width: 80%;"
{| class="wikitable" style="width: 80%;"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''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]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''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]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}
|}


Line 150: Line 157:
* [http://circ.ahajournals.org/content/122/24/2619 ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines]<ref name="pmid21060077">{{cite journal| author=Abraham NS, Hlatky MA, Antman EM, Bhatt DL, Bjorkman DJ, Clark CB et al.| title=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. | journal=Circulation | year= 2010 | volume= 122 | issue= 24 | pages= 2619-33 | pmid=21060077 | doi=10.1161/CIR.0b013e318202f701 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21060077  }}</ref>
* [http://circ.ahajournals.org/content/122/24/2619 ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines]<ref name="pmid21060077">{{cite journal| author=Abraham NS, Hlatky MA, Antman EM, Bhatt DL, Bjorkman DJ, Clark CB et al.| title=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. | journal=Circulation | year= 2010 | volume= 122 | issue= 24 | pages= 2619-33 | pmid=21060077 | doi=10.1161/CIR.0b013e318202f701 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21060077  }}</ref>


* [http://circ.ahajournals.org/content/117/8/1101.full.pdf ACC/AHA/Physician Consortium 2008 Clinical Performance Measures for Adults With Nonvalvular Atrial Fibrillation or Atrial Flutter]<ref name="pmid18283199">Estes NA, Halperin JL, Calkins H, Ezekowitz MD, Gitman P, Go AS et al. (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18283199 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. [http://dx.doi.org/10.1161/CIRCULATIONAHA.107.187192 DOI:10.1161/CIRCULATIONAHA.107.187192] PMID: [http://pubmed.gov/18283199 18283199]</ref>
* [http://circ.ahajournals.org/content/117/8/1101.full.pdf ACC/AHA/Physician Consortium 2008 Clinical Performance Measures for Adults With Nonvalvular Atrial Fibrillation or Atrial Flutter]<ref name="pmid18283199">Estes NA, Halperin JL, Calkins H, Ezekowitz MD, Gitman P, Go AS et al. (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18283199 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. [http://dx.doi.org/10.1161/CIRCULATIONAHA.107.187192 DOI:10.1161/CIRCULATIONAHA.107.187192] PMID: [http://pubmed.gov/18283199 18283199]</ref>


* [http://content.onlinejacc.org/cgi/reprint/48/4/e149.pdf ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation]<ref name="pmid16908781">Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16908781 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. [http://dx.doi.org/10.1161/CIRCULATIONAHA.106.177292 DOI:10.1161/CIRCULATIONAHA.106.177292] PMID: [http://pubmed.gov/16908781 16908781]</ref>
* [http://content.onlinejacc.org/cgi/reprint/48/4/e149.pdf ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation]<ref name="pmid16908781">Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16908781 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. [http://dx.doi.org/10.1161/CIRCULATIONAHA.106.177292 DOI:10.1161/CIRCULATIONAHA.106.177292] PMID: [http://pubmed.gov/16908781 16908781]</ref>

Revision as of 01:16, 9 June 2016
Resident
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Atrial fibrillation anticoagulation On the Web

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Powerpoint slides

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Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

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Risk calculators and risk factors for Atrial fibrillation anticoagulation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

Oral anticoagulation is a mainstay of atrial fibrillation management. 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 oral anticoagulation.[1]

Increasing patient age (which is associated with smaller body weight, female gender and a progressive decline in renal function) and higher INRs or greater intensity of anticoagulation are both associated with a higher risk of major bleeding. This is critical in so far as bleeding is in turn associated with non-compliance with pharmacotherapy.[1][2][3] [1][4] Given that many patients with atrial fibrillation are elderly, there is often a narrow therapeutic window in achieving the optimal INR. The optimal INR should obviously maximize efficacy in reducing the risk of stroke and simultaneously minimize the risk of bleeding. In the setting of atrial fibrillation, an INR of 2 to 3 appears to be optimal. 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.[5][6] [7][8]

Based upon the RE-LY study, dabigatran was recently approved for the treatment of non-valvular atrial fibrillation.

Anticoagualtion

Interruption of Anticoagulation with Coumadin

  • No mechanical valve, high risk of bleeding with procedure: Coumadin can be discontinued for one week without heparin bridging.
  • Presence of mechanical valve, patients with AF who are at high risk of stroke, or patients in whom coumadin must be interrupted for over a week: These patients should be administered either unfractionated heparin or low molecular weight heparin.

Investigational Antithrombin Agents

Warfarin inhibits multiple factors in the anticoagulation cascade, and dabigatran is a direct thrombin (factor 2) inhibitor. Newer agents that inhibit factor Xa are under investigation for the anticoagulation of patients with non-valvular atrial fibrillation. These agents include apixaban which is being evaluated in the Aristotle trial, edoxaban which is being evaluated in the Engage trial and rivaroxaban which was evaluated in the Rocket AF program.

  • Slides from the Rocket-AF program can be downloaded here.
  • A comparison of the RE-LY and Rocket AF trials can be found here.

Antiplatelet Therapy for Atrial Fibrillation

Aspirin Monotherapy

Aspirin monotherapy is associated with only a modest and inconsistent reduction in the risk of stroke associated with atrial fibrillation.[8][9] 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.[10][11]

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 MI 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.

Oral Anticoagulation (Coumadin) versus Dual Antiplatelet Therapy (ASA/Clopidogrel)

In the ACTIVE W trial, dual antiplatelet therapy with aspirin (75-100 mg per day) and clopidogrel (75 mg per day) was found to be statistically inferior to coumadin therapy (target INR 2.0 to 3.0) in the management of patients with atrial fibrillation who had one or more risk factors for stroke.[12] The primary endpoint of ACTIVE W was the first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. The annual risk in the coumadin group was 3.93% per year, and in the aspirin/clopidogrel group it was 5.60% per year yielding a relative risk of 1.44 (1.18-1.76; p=0.0003). The efficacy was not as great among patients who were coumadin naive, although the p-value for the interaction was negative. There was no excess bleeding among patients treated with coumadin, and in fact there was an excess of minor bleeds among patients treated with ASA and clopidogrel (13.6% / yr vs 11.5% year, p=0.0009).

When examining the data from atrial fibrillation trials, it is critical to evaluate the results in patients who were previously treated with coumadin separate from those patients who were naive to coumadin. Patients previously treated with coumadin are likely to be those patients who best tolerate coumadin and have passed their bleeding stress test and have a lower rate of bleeding on coumadin. Those patients who bleed while on coumadin have already been culled out from the population. When the data in ACTIVE W were evaluated including only those patients previously treated with coumadin (again a population to be anticipated to be at low risk of bleeding), the risk of major bleeding was indeed statistically significantly lower among patients previously treated with coumadin (p=0.03) than patients not previously treated.

The majority of the reduction in events was due to a reduction in stroke and non CNS embolization associated with coumadin therapy. The pathophysiology of stroke among patients with atrial fibrillation is thought to be embolization from clot in the left atrium. The data from ACTIVE W suggest that platelet activation and its treatment may not play a pivotal role in the treatment of mural thrombus and embolization in atrial fibrillation. Coumadin was more effective in the reduction of non disabling stroke rather than disabling stroke. There were more fatal hemorrhagic strokes (which may more often be fatal), and this may explain in part why coumadin was not associated with a reduction in mortality in the study.

While clopidogrel plus aspirin has been found to reduce the risk of recurrent myocardial infarction among patients with presumed plaque rupture and acute coronary syndromes, it is notable in ACTIVE W that the risk of myocardial infarction tended to be higher among patients treated with aspirin plus clopidogrel versus coumadin (0.86% vs 0.55%,p=0.09).[13]

Anticoagulation in end stage renal disease

Patients with end stage renal disease were excluded from the trials of warfarin in AF, as well as from the trials of the NOACs in AF. There is no high quality randomized data looking at anticoagulation in patients with AF and ESRD. Given the risk factors for kidney disease, most patients with AF and ESRD 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 ESRD given a markedly increased risk for intracranial bleeding [14][15][16][17]. This may be related to baseline bleeding propensity in ESRD from uremic platelet dysfunction as well as issues with maintaining a therapeutic INR. Use of warfarin in ESRD 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 LV 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.

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation (DO NOT EDIT)[18]

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)[19]

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[20] (DO NOT EDIT)

“
  1. Clopidogrel reduces major CV events compared with placebo or aspirin.
  2. 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.
  3. Clopidogrel alone, aspirin alone, and their combination are all associated with increased risk of GI bleeding.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Clinical decisions regarding concomitant use of PPIs and thienopyridines must balance overall risks and benefits, considering both CV and GI complications.
  9. 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.
  10. 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.
  11. The role of either pharmacogenomic testing or platelet function testing in managing therapy with thienopyridines and PPIs has not yet been established.
 ”

Sources

References

  1. ↑ 1.0 1.1 1.2 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)
  2. ↑ 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)
  3. ↑ 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)
  4. ↑ 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)
  5. ↑ 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)
  6. ↑ "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)
  7. ↑ "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)
  8. ↑ 8.0 8.1 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)
  9. ↑ "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)
  10. ↑ 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)
  11. ↑ 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.
  12. ↑ The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Lancet 2006;367:1903-12.
  13. ↑ The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Lancet 2006;367:1903-12.
  14. ↑ 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.
  15. ↑
    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.
  16. ↑ 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.
  17. ↑
    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.
  18. ↑ 18.0 18.1 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.
  19. ↑ 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)
  20. ↑ 20.0 20.1 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.
  21. ↑ 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
  22. ↑ 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
  23. ↑ 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


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