Warfarin and Direct Oral Anticoagulants
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Direct answer
Warfarin and direct oral anticoagulants are the oral options for preventing stroke in atrial fibrillation and for treating venous thromboembolism. Warfarin inhibits vitamin K-dependent clotting factors, while DOACs directly inhibit thrombin or factor Xa. Warfarin remains the only choice for mechanical heart valves and is preferred in antiphospholipid syndrome, while DOACs are contraindicated in moderate to severe rheumatic mitral stenosis and mechanical valves.
What you must remember
- Warfarin target: INR 2.0 to 3.0, aiming for 2.5, in atrial fibrillation and venous thromboembolism; mechanical mitral valves need a higher target, usually 3.0.
- Warfarin reversal: intravenous or oral vitamin K for stable patients, and four-factor prothrombin complex concentrate with vitamin K for major bleeding; fresh frozen plasma is used only when concentrate is unavailable.
- DOAC agents: dabigatran is a direct thrombin inhibitor cleared about 80 per cent by the kidney; rivaroxaban, apixaban and edoxaban are factor Xa inhibitors.
- Apixaban dose reduction: 2.5 mg twice daily in atrial fibrillation when at least two of the following are present: age 80 or older, weight 60 kg or less, and creatinine 1.5 mg/dL or more.
- DOAC reversal: idarucizumab reverses dabigatran, andexanet alfa is used for factor Xa inhibitors, and prothrombin complex concentrate is a common alternative.
- Valvular exclusion: DOACs are not used with moderate to severe mitral stenosis or mechanical prosthetic valves, and warfarin is preferred in antiphospholipid syndrome.
A 74-year-old with atrial fibrillation who weighs 58 kg
A 74-year-old woman with non-valvular atrial fibrillation weighs 58 kg and has a creatinine of 1.6 mg/dL. She meets two of the three apixaban dose-reduction criteria, namely weight 60 kg or less and creatinine 1.5 mg/dL or more, so the dose is 2.5 mg twice daily.
- Estimate renal function: Creatinine clearance is estimated before any DOAC, because dabigatran and rivaroxaban doses depend on renal function.
- Plan the switch: Switching from warfarin to a DOAC begins once the INR has fallen below 2.0 for most agents, as per product labelling.
- Adjust for interactions: Warfarin dosing is tracked against the INR, because amiodarone, metronidazole, cotrimoxazole and fluconazole raise it while rifampicin lowers it sharply.
- Review with tuberculosis treatment: The rifampicin point matters in India, because a patient on warfarin who starts antitubercular treatment can become under-anticoagulated. DOAC levels fall in the same way, so the anticoagulant should be reviewed when tuberculosis treatment begins.
- Record the baseline: Renal function, liver tests and a full blood count are recorded before choosing the agent, since they determine both dosing and bleeding risk.
Where the examiner catches the valve and the pregnancy
The commonest trap is the phrase non-valvular atrial fibrillation, and the examiner tests whether the valve is named.
- Trap: Treating rheumatic mitral stenosis as non-valvular because atrial fibrillation is present. Correct: Moderate or severe rheumatic mitral stenosis counts as valvular, so a DOAC is not used; a bioprosthetic valve is generally acceptable for a DOAC after the early post-implant period, but a mechanical valve always requires warfarin.
- Trap: Continuing warfarin through pregnancy. Correct: Warfarin is teratogenic when given between weeks 6 and 12 and is avoided, and low-molecular-weight heparin is preferred because DOACs are not recommended in pregnancy or breastfeeding.
- Trap: Choosing a DOAC for antiphospholipid syndrome. Correct: Warfarin is preferred, particularly in triple-positive disease, because DOACs have been associated with more recurrent thrombosis in that group.
Frequently asked questions
What INR target is used for atrial fibrillation on warfarin?
An INR target of 2.0 to 3.0, aiming for 2.5, is used for non-valvular atrial fibrillation on warfarin. Mechanical mitral valves need a higher target, usually 3.0, and the examiner may expect that distinction.
How is warfarin reversed in major bleeding?
Major warfarin-associated bleeding is reversed with four-factor prothrombin complex concentrate together with intravenous vitamin K, with fresh frozen plasma reserved for when concentrate is unavailable. The INR is rechecked to confirm that reversal has occurred.
Which DOAC is reversed by idarucizumab?
Idarucizumab reverses dabigatran, a direct thrombin inhibitor, and is the specific antidote for that agent. Andexanet alfa is used for factor Xa inhibitors such as rivaroxaban and apixaban, with prothrombin complex concentrate as a common alternative.
Why are DOACs avoided with mechanical heart valves?
DOACs are avoided with mechanical heart valves because studies showed more thrombotic and valve-related events than with warfarin in these patients. Warfarin remains the anticoagulant of choice for mechanical valves.