A Patient’s Guide to Taking the Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) for Atrial Fibrillation

Introduction

Having atrial fibrillation, an irregular heart rhythm, increases your risk of having a stroke. This irregular beating of the heart affects blood flow in the top chambers of the heart and can cause blood cells to collect and stick together, which increases the risk of a blood clot forming. These blood clots may then be carried in the bloodstream to the brain and if large enough, can block an artery in the brain, resulting in a stroke. Oral anticoagulant drugs (commonly called ‘blood-thinners’) are used to help prevent strokes by causing the blood to take longer to clot. Two groups of oral anticoagulant drugs are used: (1) vitamin K antagonists (VKA) (warfarin/Coumadin®), and (2) non-VKA oral anticoagulants (NOACs). This Cardiology Patient Page will focus on NOACs.

What NOACs are available?

There are currently 4 NOACs available for healthcare providers to prescribe for patients with atrial fibrillation (see Table 1): dabigatran (Pradaxa®), rivaroxaban (Xarelto®), apixaban (Eliquis®), and edoxaban (Lixiana [Europe/Asia], Savaysa [Nth Am]). Each drug is available in two doses. Your healthcare provider will explain which is the most appropriate drug and dose for you, and why.

Table 1.

How and when to take the NOAC and reasons for dose reductions

Generic name	Dabigatran	Rivaroxaban	Apixaban	Edoxaban (Lixiana [Europe/Asia], Savaysa [Nth Am])
	Pradaxa ®	Xarelto ®	Eliquis ®	Lixiana ®
Dose	150mg	20mg	5mg	60 mg
	110mg (Europe) 75mg (US)	15mg	2.5mg	30 mg
Frequency	Twice daily	Once daily	Twice daily	Once daily
When to take medication	Morning & evening	Once per day	Morning & evening	Once per day
	12-hour gap between doses (ideally)	-	12-hour gap between doses (ideally)	-
	Same times each day	Same time each day	Same times each day	Same time each day
How to take medication	Swallow capsule whole with water	Swallow tablet whole with water	Swallow tablet whole with water	Swallow tablet whole with water
	With food	With or after food	With or without food	With or after food
Missed dose	Less than 6 hours to next dose DO NOT TAKE	Take as soon as remembered	Take as soon as remembered	Take as soon as remembered
	More than 6 hours to next dose TAKE	Next tablet the following day	Continue twice daily	Next tablet the following day
Extra dose taken accidentally	Contact healthcare provider	Contact healthcare provider	Contact healthcare provider	Contact health care provider
Dose reduction recommended	Aged 80 years or older	Moderate reduction in kidney function	Moderate reduction in kidney function	Moderate reduction in kidney function
	Moderate reduction in kidney function	High risk of bleeding	High risk of bleeding	Weight ≤ 60 kg (132 lbs)
	On verapamil (Cordilox)			On verapamil (Cordilox), quinidine, or dronedarone (Multaq)
	High risk of bleeding

Brand names of drugs in italics

Am I eligible for a NOAC?

You may be eligible for a NOAC if you have atrial fibrillation, plus one or more of the following stroke risk factors: heart failure, high blood pressure, aged 65 years or older, diabetes, previous stroke (or mini-stroke/pin-stroke), vascular disease (blockages in your leg arteries or a heart attack, or both), or are female. You can calculate your own risk of stroke by completing the questions in Box 1. You should discuss whether you are eligible to receive a NOAC for stroke prevention with your doctor, because these medications may not be suitable for everyone who has atrial fibrillation.

Box 1. Calculating your own risk of stroke using the CHA₂DS₂-VASc score.

Read each question. If you have the risk factor, the score for each is given in the last column. If you don’t have the risk factor you score 0 for each. Your total score can range from 0 to 9. The higher you score, the greater your risk of stroke. If you score 1 or more, you should discuss the NOACs with your healthcare provider. If you are a woman, you must have 1 or more of the other stroke risk factors to be eligible for a NOAC.

			Score
C	Congestive heart failure	Do you have heart failure or have you ever been told you have had heart failure?	1
H	Hypertension	Do you have high blood pressure or take medication to help control your blood pressure?	1
A	Age 75 or older	Are you aged 75 years or older?	2
D	Diabetes	Do you have diabetes?	1
S	Stroke/Transient Ischemic attack	Have you ever had a stroke or a transient ischaemic attack (‘mini-stroke/pin-stroke’)?	2
V	Vascular disease	Do you have blockages in your leg arteries or have you had a heart attack, or have you been told you have ‘hardening of the arteries’? (if yes, to 1 or more)	1
A	Age 65-74 years	Are you aged 65 to 74 years?	1
Sc	Sex category	Are you female?	1
Maximum total score			9

How and when to take the medication

It is important that you take this medication EXACTLY as prescribed, and remember to take it EVERY day (see Tables 1 and 2). You will need to take your NOAC for the rest of your life or until your healthcare provider tells you to stop.

Table 2.

Important Do’s and Don’ts

What to Do	What not to do
■ Take medication EXACTLY as prescribed	■ Never double up a dose to make up for a missed dose
■ Take medication EVERY day – don’t miss any doses	■ Don’t stop taking your NOAC without consulting your healthcare provider
■ Look out for sign and symptoms of bleeding	■ Don’t start any new medications, supplements, or herbal remedies without first checking with your healthcare provider or pharmacist
■ If bleeding occurs, seek medical attention
■ Tell all healthcare providers you are taking a NOAC
■ Carry the Patient Alert Card and/or wear Patient Alert Bracelet
■ Educate yourself about atrial fibrillation and NOACs

Dabigatran and apixaban are taken twice daily, ideally with 12 hours between the doses. Rivaroxaban and edoxaban are taken once daily (see Table 1). Take the medication at roughly the same time(s) every day, so that the dose(s) of the drug are evenly spaced throughout the day. For example, for dabigatran or apixaban, take one tablet at 8am and one tablet at 8pm; for edoxaban, take one tablet at 9am every day; for rivaroxaban, take one tablet daily with the dinner meal.

Dabigatran should be taken with food to prevent stomach upset, and apixaban can be taken with or without food. Rivaroxaban and edoxaban must be taken with or after food. Swallow the tablet whole, do NOT bite or chew it, and wash down with water.

If you take an extra dose(s) in error, contact your healthcare provider immediately.

What to do if a dose is missed

If you miss a dose of rivaroxaban, apixaban, or edoxaban take one dose as soon as you remember. If you miss a dose of dabigatran, as long as there are 6 hours or more until your next scheduled dose is due, you can take one tablet, otherwise, DO NOT take the dose you have missed. Just take the next dose when scheduled.

Never miss a dose or run out of the medication. Make sure you have a repeat prescription to help reduce your risk of stroke.

What are the side effects?

NOACs are usually well-tolerated with few side effects. The main side effect is bleeding, which can range from minor (e.g., slight bruising or occasional bleeding from the gums when bruising teeth) to serious bleeding (e.g., vomiting blood, blood in the stools/urine, or bleeding inside your head).

There are currently no officially approved antidotes for the NOACs, but companies are testing reversal agents that could become available soon. NOACs are eliminated from the body quickly, so bleeding usually stops by itself. Doctors use other medications to try to stop the bleeding, especially “prothrombin complex concentrates.”

When to seek immediate medical attention (call 911/emergency services)

If you are taking a NOAC and experience ANY of the following:

• ■ Vomiting blood or coughing up dark brown (like dark coffee) stomach content

• ■ Blood in your urine (red or dark brown) or black or bloody stools

• ■ Bleeding from your rectum

• ■ Severe nose bleed, which does not stop quickly despite pressure (within 10 minutes)

• ■ Any other visible bleeding that will not stop

• ■ Excessive tiredness, weakness, dizziness or unexplained swelling

• ■ Fall or injury to the head

• ■ Severe or usual headache, often with neck stiffness or other stroke symptoms (slurred speech, arm weakness, facial drooping) – these symptoms could be due to bleeding in the brain

NOAC and lifestyle

Pregnancy and breast-feeding

NOACs are NOT recommended during pregnancy. If you are a woman of child-bearing age and wish to become pregnant, you should NOT take a NOAC.

Surgery/dental and other medical procedures

You should inform your healthcare providers that you are taking a NOAC. If you need to have surgery, dental, or another medical procedure, then you may need to stop taking your NOAC beforehand.

Other medications

You should avoid taking aspirin, warfarin (Coumadin®) and non-steroidal anti-inflammatory medications such as ibuprofen, together with a NOAC, as this will increase the risk of bleeding. However, your healthcare provider may ask you take a NOAC together with aspirin and/or clopidogrel (Plavix®) for a specific reason (for example, after you have had a stent inserted into an artery in your coronary artery).

If you are prescribed any new medication or want to buy any herbal remedies or over-the-counter medications (including common pain-relief medications or cough medicine), ask your healthcare provider or pharmacist to check that they can be taken with your NOAC.

Alcohol

Large amounts of alcohol may cause or trigger atrial fibrillation and can also increase the risk of bleeding. Therefore, it is recommended that you no more than one drink daily.

Food

There are no foods to avoid when taking a NOAC because these drugs do not interact with food. In particular, you can have as many green, leafy vegetables as you wish.

Travel

There is no reason to restrict travel while taking a NOAC. Check with your healthcare provider before travelling, and make sure you have all your medication with you so that you do not run out of medication while you are away. Take a summary of your medical history and medication. Carry medication in your hand-luggage to keep these with you.

Other activities

Avoid activities where the risk of a fall or serious injury is possible (e.g., contact sports, rock-climbing, etc.).

Switching from warfarin to a NOAC

If you are switching from warfarin (Coumadin®) to a NOAC, your healthcare provider will ask you to stop taking warfarin. You will have a blood test to check your international normalized ratio (INR) - a test of the time it takes your blood to clot. Dabigatran or apixaban can be started once your INR is less than 2.0. Rivaroxaban and edoxaban can be started once your INR is 3.0 or less.

Monitoring

Your healthcare provider will monitor your kidney function while you are taking a NOAC as part of routine blood tests. How often you need to have this test done will depend on your kidney function when you start taking the NOAC and other health conditions you may have. It is very important that you tell your healthcare provider about any new medical condition(s).

Your healthcare provider may need to lower the dose of your NOAC (see Table 1) or stop it completely if your kidney function decreases too much (to a level where it would be unsafe to continue taking the NOAC). If this happens, your healthcare provider will discuss this with you and suggest an alternative treatment.

Where to get more information

The best person to ask is your healthcare provider because they have detailed information about your specific health issues and advice may vary from patient to patient, depending on your underlying health conditions.

Additional resources

There are also a number of internet sites that have information about atrial fibrillation and NOACs. The ones listed below provide reliable information.

• ■ American Heart Association. Available at: http://www.heart.org/HEARTORG

• ■ European Heart Rhythm Association. Atrial fibrillation. Available at: http://www.afibmatters.org

• ■ National Institute of Health Care Excellence (NICE). Patient Decision Aid. Available at: http://www.nice.org.uk/guidance/cg180/resources/cg180-atrial-fibrillation-update-patient-decision-aid2

• ■ Heart Rhythm Society. What is Atrial Fibrillation? Available at: http://www.hrsonline.org/Patient-Resources/Heart-Diseases-Disorders/Atrial-Fibrillation-AFib#axzz39922w1JZ

• ■ Atrial Fibrillation Association. Available at: http://www.atrialfibrillation.org.uk

• ■ StopAFib website. Available at: http://www.stopafib.org

If you take warfarin (Coumadin®), these articles may be of interest:

• ■ Fiumara K, Goldhaber SZ. A patient’s guide to taking coumadin/warfarin. Circulation. 2009; 119:e220-e222.

• ■ Bussey HI, Bussey M. Cardiology patient page. Warfarin management: international normalized ratio self-testing and warfarin self-dosing. Circulation. 2012; 126:e52-54.