Update to anticoagulation in atrial fibrillation

Let’s start with a patient case. A 72 year old female presents to the hospital with fatigue, palpitations, and shortness of breath that has occurred intermittently over the last two weeks.  Her PMH is significant for anxiety, seasonal allergies, and PAD which is rarely symptomatic and not lifestyle-limiting.  She is admitted to the hospital with the diagnosis new-onset atrial fibrillation.  What anticoagulation strategy is recommended for someone like this?

This pharmacy pearl highlights just a few of the key points regarding anticoagulation from the 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation which was just published in April of this year.¹  There are several differences between this newest guideline and the most recent version of the Chest guidelines from 2012 (which only addressed warfarin and dabigatran since it was the only new oral anticoagulant approved at the time).  Note that this entire summary will be referring to nonvalvular atrial fibrillation.

Which stroke risk stratification tool to use?

• In patients with nonvalvular atrial fibrillation, the CHA2DS2-VASc score is recommended for assessment of stroke risk (Class I recommendation, level of evidence B).

Definition and scores for CHA2DS2-VASc

Heart failure	1
HTN	1
Age ≥75	2
Diabetes mellitus	1
Stroke/TIA/Thromboembolism	2
Vascular disease (eg. MI, PAD, aortic plaque)	1
Age 65-74	1
Female	1
Maximum total	9

The CHA2DS2-VASc was found to better discriminate stroke risk in patients found to be “intermediate” when using the CHADS2 score, so now it is the preferred risk stratification tool.

  

What anticoagulation strategy is recommended based on the CHA2DS2-VASc risk?

CHA2DS2-VASc	Recommendation	Certainty of treatment effect	Level of evidence
0	Reasonable to omit antithrombotic therapy	Class IIa	B
1	No therapy or oral antithrombotic or aspirin	Class IIb	C
≥2	Anticoagulation is recommended*	Class I	Warfarin: A Dabigatran: B Rivaroxaban: B Apixaban: B

*Choices for anticoagulation include warfarin, dabigatran, rivaroxaban, or apixaban (all three of the new oral anticoagulants are level of evidence B meaning limited populations studied).  Note that all four choices are Class I recommendations (Benefit >>>Risk) so they can all be first line treatment depending on patient factors like comorbid disease states, drug interactions, cost, adherence, side effects tolerability, etc.. 

• If a patient on warfarin is unable to maintain a therapeutic INR (defined as a goal INR 2.0-3.0 – no surprises there), then one of the three new oral anticoagulants are recommended.

  

There are a few more recommendations for patients with ESRD on HD and those undergoing PCI:

For patients with ESRD on HD who require anticoagulation, here is the recommendation:

Warfarin	Recommended
Dabigatran	Not recommended
Rivaroxaban	Not recommended
Apixaban	Acceptable to use; however, there is no published data in this setting

*All three new oral anticoagulants require a dosage adjustment at a certain extent of renal dysfunction.

For patients undergoing PCI and have a CHA2DS2-VASc ≥2 [where triple therapy would be recommended (two antiplatelet agents plus an oral anticoagulant)]:

• It is reasonable to use clopidogrel 75 mg once daily without aspirin.
• This was based on a study that found bleeding rates of 44.4% with triple therapy (ASA + clopidogrel + warfarin) and only 19.4% with double therapy (clopidogrel + warfarin) after PCI (p<0.0001), but thrombotic and thromboembolic rates did not differ.²
• Of note, the new anticoagulants have not been studied in the context of AF and ACS so no recommendation on their use can be made.

Back to the patient case:

Using the old risk stratification tool (CHADS2) this patient would have scored a zero and the recommended anticoagulation strategy would have been to not use any of the oral anticoagulants.  This seemingly low risk patient is better stratified with the CHA2DS2-VASc where her score would be 3 (age, PAD, and female) in which full anticoagulation is recommended.  There is no history of kidney insufficiency, no drug interactions, and no cost or adherence issues obvious at this time.  Warfarin or any of the three new agents are all first line and the decision on antithrombotic therapy should be individualized based on shared decision making considering the patient’s values and preferences (also a Class I recommendation).  See the current prescribing information for each drug for dosing recommendations.

Take home points:

• Use the CHA2DS2-VASc to stratify patients’ stroke risk.
• For patients with nonvalvular atrial fibrillation with a CHA2DS2-VASc ≥2, anticoagulation is recommended.
• Warfarin, dabigatran, rivaroxaban, and apixaban are all first line when anticoagulation is recommended and the ideal choice depends on numerous patient-specific factors.
• All of the new oral anticoagulants need to be adjusted in renal dysfunction and warfarin is specifically recommended in ESRD on HD.
• The only oral anticoagulant to have been studied in a wide variety of patients is warfarin.

References:

1.  January CT, Wann LS, Alpert JS, et al.  2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation.  Circulation 2014 April.

2.  Dewilde WJ, Oirbans T, Verheugt FW, et al.  Use of oral clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial.  Lancet 2013;381:1107-15.

photo by Andrew Mason