This document provides guidance on the use and management of non-vitamin K antagonist oral anticoagulants (NOACs) for atrial fibrillation patients. It recommends against their use for patients with mechanical heart valves or severe mitral stenosis. It outlines the need for baseline testing and monitoring of renal and liver function when prescribing NOACs. Dosing should be based on renal clearance and some NOACs are contraindicated for those with severe renal or liver impairment. Drug-drug interactions and reversal agents in bleeding events are also discussed.

1. Use of NOACs is contraindicated for
AF patients with mechanical
prosthetic valves or moderate-
severe mitral stenosis (usually of
rheumatic origin).
Although there are limited data for patients
with bioprosthetic valves, mitral valve repair,
or transcatheter aortic valve replacement,
use is acceptable.

2. Structured follow-up is recommended
for patients on chronic NOAC use
This includes
• documentation of anticoagulation indication,
• checking baseline laboratory studies
(hemoglobin, renal and liver function,
coagulation panel),
• providing education, and coordinating follow-up
with at least once-yearly laboratory studies.
• Repeat laboratory testing should be performed
more frequently for patients with baseline renal
dysfunction or the elderly.

3. It is important to calculate renal function using
the Cockcroft-Gault equation. This is used to
appropriately dose NOACs. Use of NOACs is not
recommended for patients with creatinine
clearance <15-30 ml/min or on dialysis.
Note: In the United States, apixaban is dosed based
on serum creatinine level, weight, and age (this
differs from European dosing). Also, both apixaban
and rivaroxaban are Food and Drug Administration
(FDA) approved for use with dialysis.

4. It is also important to check baseline
liver function before starting NOACs.
NOACs are contraindicated for patients with
Child-Pugh category C hepatic insufficiency.
Rivaroxaban is also contraindicated in Child-
Pugh category B hepatic insufficiency.

5. When switching from a NOAC to warfarin, warfarin
should be started and the NOAC continued until the INR
is ≥2. Repeat the INR 1-3 days after stopping NOAC to
ensure INR remains therapeutic.
When switching from warfarin to a NOAC, the NOAC
should be started when the international normalized
ratio (INR) is <2.5.

6. Although NOACs have fewer drug-drug interactions
than warfarin, there are still important drug-drug
interactions to monitor.
These include the P-glycoprotein and CYP3A4 interacting
medicines. Important examples include avoiding
concurrent use of
• dronedarone,
• rifampin,
• many HIV protease inhibitors,
• itraconazole,
• ketoconazole,
• voriconazole,
• St. John’s wort, and
• dexamethasone.

7. In the case of a nonlife-threatening major bleeding event,
plasma levels of NOACs should normalize within 12-24 hours
for patients with normal renal function. It may take longer for
patients with renal insufficiency, particularly for dabigatran.
In the case of a life-threatening major bleeding event,
patients on dabigatran can be given idarucizumab 5 mg IV in
two doses no more than 15 minutes apart. Patients taking
factor Xa inhibitors should be given prothrombin complex
concentrate 50 U/kg. All patients should receive supportive
measures, including mechanical compression and endoscopic
or surgical hemostasis (if applicable).
Following a major gastrointestinal bleeding event, NOACs should be
restarted as early as feasible (usually 4-7 days) if the risk of stroke
persists and outweighs the risk of recurrent bleeding.

8. • Most patients taking NOACs can safely undergo
surgical procedures with a 24- to 48-hour pre-
procedure hold.
• Longer hold times may be necessary for patients
taking dabigatran who have chronic kidney
disease.
• No bridging heparin is needed for NOAC-treated
patients.
• Resume full-dose NOAC within 72 hours post-
procedure, once the bleeding risk is appropriate.

9. For patients taking NOAC who present with
an acute coronary syndrome, primary
percutaneous coronary intervention (PCI) can
be performed (preferably using a radial
approach) emergently for ST-segment
elevation myocardial infarction (STEMI)
patients or delayed for 24-48 hours in stable
NSTEMI patients.
Consider a proton pump inhibitor for
patients taking combined NOAC with
antiplatelet medications.

10. After 1 year, all patients should
continue on NOAC monotherapy.
For patients taking NOAC with single or dual
antiplatelet therapy, shorter courses of
antiplatelets are recommended. Patients with
elective PCI may benefit from dual therapy
(NOAC plus clopidogrel from discharge through
1 year). Patients with acute coronary syndromes
who undergo PCI should receive triple therapy
for up to 3 months, then switch to dual therapy
(NOAC plus clopidogrel) until 1 year.

11. For patients taking NOAC who present with an acute ischemic
stroke, proceed with thrombolysis if the NOAC plasma level is
below the lower limit of detection or if the last intake was >48
hours prior and renal function is normal. Otherwise consider
thrombolysis in select patients after NOAC reversal or use of
endovascular therapy.
For patients taking NOACs who present with an acute
ischemic stroke, consider re-starting NOACs after 3-14
days, depending on the degree of neurologic deficit
and excluding any hemorrhagic transformation on
brain computed tomography.