ORAL ANTICOAGULATION GUIDELINE Flashcards
Anti-phospholipid syndrome
Preferred anticoagulant
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
CAD
Preferred anticoagulant
Warfarin, apixaban, rivaroxaban, edoxaban
CAD events appear to occur more often with dabigatran than warfarin.
Cancer-associated venous thrombosis
Preferred anticoagulant
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.
DVT
Preferred anticoagulant
DOAC
Drugs of choice if no contraindications and if patients can afford it.
Dyspepsia
Preferred anticoagulant
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).
Extremes in weight
Preferred anticoagulant
warfarin
Patients with weighs <50 kg and >120 kg are not studied for DOACs
History of GI bleeding
Preferred anticoagulant
Warfarin, apixaban
Dabigatran, rivaroxaban, and edoxaban associated with more GI bleeding than warfarin in clinical trials.
Moderate-Severe hepatic impairment
Preferred anticoagulant
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.
Once daily oral therapy preferred
Preferred anticoagulant
Warfarin, rivaroxaban, edoxaban
Warfarin, dabigatran, and edoxaban may require initial parenteral therapy for treatment of acute thrombosis.
Poor adherence
Preferred anticoagulant
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.
Pregnancy or pregnancy risk
Preferred anticoagulant
LMWH
Potential for other agents to cross the placenta
Requirement for adherence aid such as medication pill box
Preferred anticoagulant
Warfarin, apixaban, rivaroxaban, edoxaban
Severe renal impairment
Preferred anticoagulant
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
Stroke prevention in patients with atrial fibrillation and CrCl > 95 mL/min
Preferred anticoagulant
Warfarin, apixaban, rivaroxaban, dabigatran
Edoxaban contraindicated in these patients.
Thrombocytopenia
Preferred anticoagulant
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.
Valvular disease
Preferred anticoagulant
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.
Warfarin initial starting dose for most patients
starting dose for most patients is 5mg
Initial loading dose in yound healthy patients with acure thrombo embolism
7.5mg-10mg may be considered
When to consider initiatl starting doses of 2.5 mg
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
Apixaban (Eliquis®)
DVT/PE
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.
Apixaban (Eliquis®)
Non-valvular atrial fibrillation
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
Apixaban (Eliquis®)
Post-op venous thromboprophylaxis: Hip or knee replacement surgery:
2.5 mg PO BID beginning 12-24 hrs post-op -Duration: 35 days (hip), 12 days (knee)
Rivaroxaban (Xarelto®)
DVT/PE: -
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
Rivaroxaban (Xarelto®)
Non-valvular atrial fibrillation:
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
Rivaroxaban (Xarelto®)
Post-op DVT thromboprophylaxis: Hip or knee replacement
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
FLAMES
Strong inhibitors and inducers of CYP2C9 and CYP3A4.
Major: “FLAMES”: Fluconazole (azoles), Levofloxacin (fluoroquinolones), Amiodarone, Metronidazole, Erythromycin (or clarithromycin), Sulfamethoxazole/trimethoprim
Apixaban (ARISTOTLE) AF
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
Dabigatran (RE-LY) AF
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
Edoxaban (ENGAGE-AF)
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
Rivaroxaban (ROCKET-AF)
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
INR > 10; no significant bleeding
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
INR above therapeutic range but < 4.5; no significant bleeding
Lower dose or omit next dose
If only minimally above therapeutic range, no dose reduction may be required
INR > 4.5 but < 10; no significant bleeding
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
Dabigatran
Reversal agent?
Idarucizumab (Praxbind®)
Apixaban Edoxaban Rivaroxaban
Reversal agent?
Andexanet alfa
