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Question 1 : Concerning atrial fibrillation treatment, which of the following statements is FALSE?
- The Canadian Cardiovascular Society recommends DOACs as a first-line treatment in patients with atrial fibrillation without a prosthetic valve, rheumatic mitral stenosis nor CrCl < 30 mL/min.
- All patients suffering from non valvular AF should receive a DOAC rather than warfarin.
- The thrombotic risks of patients suffering from AF can be estimated with the CHADS2 and the CHA2DS2-VASc score.
- A previous stroke is both a thrombotic risk factor in the CHADS2 score and a bleeding risk factor in the HAS-BLED score.
Justification: Even if DOACs are recommended as first line treatment of AF in the CCS 2016 guidelines, warfarin is preferable for certain patients, such as those with moderate renal impairment, those who are nonadhering to DOAC treatment or those taking drugs that cause a clinical significant interaction with DOACs.
Question 2 : Concerning differences between anticoagulants, which of the following statements is FALSE?
- Dabigatran is the DOAC most associated with dyspepsia because of its formulation made to increase gastric pH.
- Dabigatran is mostly excreted by the kidneys and thus should be stopped earlier than the other DOACs before a surgical procedure in patients with renal insufficiency.
- The 20mg tablets of rivaroxaban must be taken with food to ensure their efficacy.
- Rivaroxaban, edoxaban and apixaban can be neutralized by the andexanet alfa.
Justification: Dabigatran capsules contain tartric acid that decreases gastric pH, which could explain dyspepsia linked to this DOAC.
Question 3 : Which of the following reasons would NOT justify a switch from warfarin to a DOAC in patients that do not have contraindications to DOACs?
- An INR difficult to stabilize within the therapeutic range
- Patients for which periodic blood tests are problematic or impossible
- Patients whom are non-adherent to their warfarin treatment
- Patients that often miss their INR blood tests
Justification: Since warfarin’s half-life is long and that of DOACs is short, it would be riskier for a non-observant patient to receive a DOAC since plasma concentrations decrease with only one missed dose. Also, by means of a blood test, we can follow-up on INR levels for warfarin whereas there is no test to measure the efficacy of DOACs.
Question 4 : Concerning venous thromboembolism treatment, which of the following statements is TRUE?
- For deep vein thrombosis, treatment with apixaban is preferred to that of warfarin in patients with cancer since it has shown a superior reduction in the risk of recurrent events.
- In regards to venous thromboembolism, dabigatran demonstrated a reduction in major bleeding risks compared to warfarin.
- In regards to venous thromboembolism, warfarin is recommended as first-line therapy because no DOAC was proven superior.
- Apixaban and rivaroxaban can be directly initiated (without initial treatment with heparin) when treating a venous thromboembolism event.
Justification: Rivaroxaban and apixaban were studied as initial treatment for VTE; heparin is therefore not needed at treatment initiation of these 2 DOACs according to the Canadian monographs and the CHEST 2016 guidelines.
Question 5 : Concerning anticoagulant interactions, which of the following statements is FALSE?
- In general, DOACs have less drug-drug interactions compared to warfarin.
- A single dose of fluconazole can be given to patients taking any of the DOACs.
- Rivaroxaban and antacids must be administered at least 2 hours apart.
- A treatment with a strong CYP3A4 and P-gp inhibitor should be avoided in patients receiving any DOAC.
Justification: The interaction between antacids and DOACs exists only with dabigatran since acidity is necessary for its absorption.
Question 6: Which of the following statements is TRUE?
- Treatment with warfarin is preferred over DOACs in patients with a BMI ≥ 35.
- For the continued prevention of recurrent events (beyond the first 6 months of treatment) an extended therapy of apixaban at 5mg bid is recommended.
- Bridging with heparin according to protocol is recommended in patients that must temporarily stop their DOAC in a perioperative setting if their CHADS2 score is 4.
- A reduction in DOAC dosage should be made in patients already taking diltiazem since the latter is a moderate inhibitor of CYP3A4 that can increase DOAC plasma concentrations.
- With regards to atrial fibrillation, the risk of intracranial bleeding is reduced when receiving any of the DOACs compared to warfarin.
Justification: A reduction of intracranial bleeding risk was demonstrated with apixaban, dabigatran, edoxaban and rivaroxaban in the ARISTOTLE, RE-LY, ENGAGE-AF and ROCKET-AF trials.
Question 7 : In regards to edoxaban, which of the following statements is FALSE?
- As opposed to the Canadian monograph, the American monograph recommends avoiding its use if the CrCl is above 95ml/min.
- It is eliminated in similar proportions by the kidneys and by the liver.
- A dosage of 60mg daily is linked to less gastrointestinal bleeding risks than with warfarin.
- If it is concomitantly taken with a strong Pgp inhibitor such as ketoconazole, it is recommended to decrease the dose from 60mg daily to 30mg daily.
Justification: No DOAC has shown to have less gastrointestinal bleeding risks than warfarin. Dabigatran 150mg twice daily, rivaroxaban and edoxaban 60mg daily have been associated to higher gastrointestinal bleeding risks than warfarin.
Question 8 : An 85 year old patient that weighs 70kg and is 1.60m tall starts a DOAC for AF and has no history of bleeding. His last measured serum creatinine is 120 µmol/L and the CrCl is 39ml/min when calculated with the Cockroft-Gault equation. Which of the following dosage reductions is NOT appropriate in his case?
- Apixaban 2.5mg twice daily
- Dabigatran 110mg twice daily
- Edoxaban 30mg once daily
- Rivaroxaban 15mg once daily
Justification: The Cl at 39ml/min justifies the dosage reductions of edoxaban and rivaroxaban. The dabigatran monograph recommends a decrease in dosage when patients are 80 years or older whereas the CCS recommends this decreased dosage for patients of 75 years or older or when the CrCl is 50ml/min or less. With regards to apixaban, the decreased dosage of 2.5mg should be used when TWO of the THREE criteria are met, which is not the case for this patient: age of 80 years or older, weight of 60kg or less and serum creatinine of 133 µmol/L or