ORAL ANTICOAGULATION GUIDELINE

Question 1

Anti-phospholipid syndrome

Preferred anticoagulant

Answer 1

Warfarin No data currently with the DOACs.

The RAPS (rivaroxaban in antiphospholipid syndrome) and ASTRO-APS (apixaban for the secondary prevention of thromboembolism among patients with antiphospholipid syndrome) trials are underway

Question 2

CAD

Preferred anticoagulant

Answer 2

Warfarin, apixaban, rivaroxaban, edoxaban

CAD events appear to occur more often with dabigatran than warfarin.

Question 3

Cancer-associated venous thrombosis

Preferred anticoagulant

Answer 3

LMWH

Clinical trials for DOACs included few cancer patients and safety and efficacy comparisons between DOACs and LMWH in this population have not been studied. LMWH is considered anticoagulant of choice for the first 3-6 months after diagnosis of cancer-associated thrombosis.

Question 4

DVT

Preferred anticoagulant

Answer 4

DOAC

Drugs of choice if no contraindications and if patients can afford it.

Question 5

Dyspepsia

Preferred anticoagulant

Answer 5

Warfarin, apixaban, rivaroxaban, edoxaban.

~11% of pts on dabigatran experienced dyspepsia in the RE-LY trial.
Post-marketing surveillance reveals 25-35% of pts experiencing GI symptoms (dyspepsia, gastritis-like symptoms).

Question 6

Extremes in weight

Preferred anticoagulant

Answer 6

warfarin

Patients with weighs <50 kg and >120 kg are not studied for DOACs

Question 7

History of GI bleeding

Preferred anticoagulant

Answer 7

Warfarin, apixaban

Dabigatran, rivaroxaban, and edoxaban associated with more GI bleeding than warfarin in clinical trials.

Question 8

Moderate-Severe hepatic impairment

Preferred anticoagulant

Answer 8

Warfarin, LMWH

Rivaroxaban and edoxaban are contraindicated in pts with moderate-severe hepatic impairment. Apixaban should be used with caution in pts with moderate dysfunction, and is contraindicated in pts with severe impairment. Patients with active liver disease were excluded from the RE-LY trial for dabigatran.

Question 9

Once daily oral therapy preferred

Preferred anticoagulant

Answer 9

Warfarin, rivaroxaban, edoxaban

Warfarin, dabigatran, and edoxaban may require initial parenteral therapy for treatment of acute thrombosis.

Question 10

Poor adherence

Preferred anticoagulant

Answer 10

Warfarin

INR monitoring can help detect adherence problems. Due to the short t1/2 of the DOACs, missing just a single dose may result in sub-therapeutic levels increasing the risk for complications such as a thrombotic event.

Question 11

Pregnancy or pregnancy risk

Preferred anticoagulant

Answer 11

LMWH

Potential for other agents to cross the placenta

Question 12

Requirement for adherence aid such as medication pill box

Preferred anticoagulant

Answer 12

Warfarin, apixaban, rivaroxaban, edoxaban

Question 13

Severe renal impairment

Preferred anticoagulant

Answer 13

Warfarin
Apixaban: excluded those with SCr > 2.5 mg/dL or CrCl < 25 mL/min from ARISTOTLE trial

Dabigatran: excluded those with CrCl < 30 mL/min from RE-LY trial

Rivaroxaban: excluded those with CrCl < 30 mL/min from ROCKET-AF trial

Edoxaban: excluded those with CrCl < 30 mL/min from ENGAGE-AF trial

Question 14

Stroke prevention in patients with atrial fibrillation and CrCl > 95 mL/min
Preferred anticoagulant

Answer 14

Warfarin, apixaban, rivaroxaban, dabigatran

Edoxaban contraindicated in these patients.

Question 15

Thrombocytopenia

Preferred anticoagulant

Answer 15

Warfarin, apixaban, edoxaban

Dabigatran: excluded those with platelet count < 100 x 109/L from RE-LY trial Rivaroxaban: excluded those with platelet count < 90 x 109/L from ROCKET-AF trial Other DOAC trials did not mention platelet count as exclusion criteria.

Question 16

Valvular disease

Preferred anticoagulant

Answer 16

DOACs not studied extensively in this patient population. Dabigatran is contraindicated for patients with mechanical valves. The RE-ALIGN trial was stopped early because patients receiving dabigatran were more likely to experience strokes, heart attacks, and blood clots forming on the mechanical heart valves than were users of the anticoagulant warfarin. There was also more bleeding after valve surgery in the dabogatran-treated group than in the warfarin-treated group.

Question 17

Warfarin initial starting dose for most patients

Answer 17

starting dose for most patients is 5mg

Question 18

Initial loading dose in yound healthy patients with acure thrombo embolism

Answer 18

7.5mg-10mg may be considered

Question 19

When to consider initiatl starting doses of 2.5 mg

Answer 19

a. Age >65 years old
b. Impaired nutritional status, low albumin , NPO > 3 days
c. Weight < 50kg
d. Uncompensated congestive heart failure
e. Liver disease (Child-Pugh Grade B/C)
f. Hyperthyroidism, untreated
g. Interacting medications known to increase warfarin activity or increase bleeding risk
h. Recent major surgery, recent history of bleeding
i. Anemia (Hct <30)
j. Renal disease (dialysis, transplant, SCr >2.6)
k. Debilitated patient
l. History of falls
m. Baseline INR above 1.3

Question 20

Apixaban (Eliquis®)

DVT/PE

Answer 20

DVT/PE: -Treatment: 10 mg PO BID x 7 days, followed by 5 mg PO BID

Secondary prevention: 2.5 mg PO BID after at least 6 months of treatment for DVT

Renal adjustment: No dosage adjustment recommended -

Note: patients with a SCr > 2.5 mg/dL or CrCl < 25 mL/min were excluded from clinical trials.

Question 21

Apixaban (Eliquis®)

Non-valvular atrial fibrillation

Answer 21

5 mg PO BID

2.5 mg PO BID 
 if patient has any 2 of the following: 
-Age ≥ 80, 
body weight ≤ 60 kg, 
or SCr ≥ 1.5 mg/dL

Question 22

Apixaban (Eliquis®)

Post-op venous thromboprophylaxis: Hip or knee replacement surgery:

Answer 22

2.5 mg PO BID beginning 12-24 hrs post-op -Duration: 35 days (hip), 12 days (knee)

Question 23

Rivaroxaban (Xarelto®)

DVT/PE: -

Answer 23

Treatment: 15 mg PO BID (with food) x 21 days, followed by 20 mg PO daily (with food)

-Secondary prevention: 20 mg PO daily (with food) after an initial 6 months of treatment

Renal adjustment: CrCl < 30mL/min: avoid use

Question 24

Rivaroxaban (Xarelto®)

Non-valvular atrial fibrillation:

Answer 24

20 mg PO daily with evening meal

Renal adjustment:
-CrCl 15-50 mL/min: 15 mg PO daily with evening meal

-CrCl < 15 mL/min and/or

ESRD requiring hemodialysis: avoid use

Question 25

Rivaroxaban (Xarelto®)

Post-op DVT thromboprophylaxis: Hip or knee replacement

Answer 25

10 mg PO daily beginning 6-10 hrs post-op

Duration: 35 days (hip), 12-14 days (knee)

Renal adjustment: -CrCl 30-50 mL/min: no dosage adjustment necessary, use with caution -CrCl < 30 mL/min: avoid use

Question 26

FLAMES

Answer 26

Strong inhibitors and inducers of CYP2C9 and CYP3A4.

Major: “FLAMES”: Fluconazole (azoles), Levofloxacin (fluoroquinolones), Amiodarone, Metronidazole, Erythromycin (or clarithromycin), Sulfamethoxazole/trimethoprim

Question 27

Apixaban (ARISTOTLE) AF

Answer 27

Primary outcome: stroke or systemic embolism
Apixaban (212 events) v. warfarin (265 events)
HR 0.79 (0.66-0.95)
p = 0.01 for superiority

Lower rates of major bleeding

Lower rates of intracranial bleeding:

No difference in GI bleeding

Question 28

Dabigatran (RE-LY) AF

Answer 28

Primary outcome: stroke or systemic embolism Dabigatran 150 mg (134 events) v. warfarin (199 events) RR 0.66 (0.53-0.82) p < 0.001 for superiority

No difference in major bleeding:

Lower rates of intracranial bleeding:

Higher rates of GI bleeding

Question 29

Edoxaban (ENGAGE-AF)

Answer 29

Primary outcome: stroke or systemic embolism.
Edoxaban 60 mg (182 events) v. warfarin (232 events)
HR 0.79 (0.63-0.99)
p < 0.001 for non-inferiority

Lower rates of major bleeding

Lower rates of intracranial bleeding

Higher rate of GI bleeding

Question 30

Rivaroxaban (ROCKET-AF)

Answer 30

Primary outcome: stroke or systemic embolism. Rivaroxaban (188 events) v. warfarin (241 events) HR 0.79 (0.66-0.96) p < 0.001 for non-inferiority

No difference in major and non-major clinically relevant bleeds

Lower rates of intracranial bleeding

Higher rates of GI bleeding

Question 31

INR > 10; no significant bleeding

Answer 31

Hold warfarin therapy

Treat with ORAL vitamin K (eg,. 2.5-5 mg vitamin K1 orally); anticipate INR to reduce substantially in 24-48 hrs. May administer additional vitamin K if necessary

Question 32

INR above therapeutic range but < 4.5; no significant bleeding

Answer 32

Lower dose or omit next dose

If only minimally above therapeutic range, no dose reduction may be required

Question 33

INR > 4.5 but < 10; no significant bleeding

Answer 33

Omit next one or two doses; resume therapy at an appropriately adjusted dose when INR at a therapeutic level

Recommend against the use of vitamin K

Question 34

Dabigatran

Reversal agent?

Answer 34

Idarucizumab (Praxbind®)

Question 35

Apixaban Edoxaban Rivaroxaban

Reversal agent?

Answer 35

Andexanet alfa