Novel Oral Anticoagulants and Food Intake: Does It Matter?

A 62-year-old woman, Mrs. Brown, comes to you as a new patient. She has a history of gastrointestinal reflux disease (GERD) and atrial fibrillation for the last 7 years and had a stroke about a year ago. Because she previously had aCHADS₂ score of 0, her primary care physician had not initiated therapeutic anticoagulation. After examining her you calculate her CHADS₂ score which is now 2. You decide that she has sufficient risk to warrant anticoagulation and choose one of the novel anticoagulants (NOACs) to begin therapy.  

As you are writing the prescription, she asks you whether she should take her anticoagulant pills with meals or whether she can take them at any time of day.  What do you advise her?

A. There is no relationship between any of the NOACs with food intake so she can take them whenever they are convenient for her.
B. NOACs should always be taken with food because they can cause GI upset.
C. NOACs should always be taken with food because their bioavailability can vary depending on food intake.
D. It depends; certain NOACs should be taken with food but not all.

Please leave your comment below. Then, click here for answer and explanation.

Answer: D. It depends; certain NOACs should be taken with food, but not all.

The European Heart Rhythm Society, in its practical guide on the use of NOACs, offers official recommendations on which agents should be taken with or without food.  Rivaroxaban, a factor Xa inhibitor, has an oral bioavailability of ~100% with food but only ~66% without food.  Therefore, it is mandatory to take this medication with food since food its increases absorption by 39%. On the other hand, apixaban, also a factor Xa inhibitor, and dabigatran, a direct thrombin inhibitor, need not be taken with food because there is no effect on their bioavailabilty or absorption based on food intake.
 
Mrs. Brown also asks you about whether these medications are known to cause stomach upset.  She is currently taking omeprazole 40 mg twice daily for her known history of GERD.  What do you tell her?

Of the NOACs, only dabigatran has been associated with dyspepsia (in 5% to 10% of patients).  Therefore, even though there is no mandate that it be taken with food, (as with rivaroxaban) it can be if necessary to alleviate this adverse effect without affecting bioavailability. It is also the only NOAC that exhibits a 12% to 30% decrease in absorption when taken with a H₂-blocker or a proton pump inhibitor.  Although no formal dose adjustment is necessary, it is important to keep this in mind for these patients.

For Mrs. Brown, who has a history of dyspepsia and is on a proton pump inhibitor, perhaps apixaban or rivaroxaban would be most appropriate. Before you give her the prescription, you advise her on the above and schedule her for baseline blood tests and follow-up in your office in 3 months.

Reference:
Heidbuchel H, Verhamme P, Alings M, et al. EHRA Practical Guide on the Use of New Oral Anticoagulants in Patients with Non-Valvular Atrial Fibrillation: Executive Summary. Eur Heart J. 2013;10.1093/eurheartj/eht134. (Full text)