Direct Oral Anticoagulant Initiation

Direct oral anticoagulants are started after checking that the indication is suitable, the dose matches kidney function, weight and age, and no interacting drug or contraindication is present. Safe initiation also needs patient teaching and a plan for follow-up.

Do not use a direct oral anticoagulant for: mechanical heart valves, moderate to severe mitral stenosis, triple-positive antiphospholipid syndrome, pregnancy and breastfeeding, severe liver disease (Child-Pugh C), and creatinine clearance under 15 mL/min (under 30 mL/min for dabigatran).

Baseline checks: creatinine clearance by Cockcroft-Gault, weight, full blood count, liver tests, pregnancy test where relevant, and a list of all drugs and herbal products.

• Atrial fibrillation: apixaban 5 mg twice daily (2.5 mg twice daily if two of age 80 or over, weight 60 kg or less, creatinine 133 micromol/L or more); rivaroxaban 20 mg once daily with the evening meal (15 mg if creatinine clearance is 15 to 50 mL/min); edoxaban 60 mg once daily (30 mg if creatinine clearance 15 to 50 mL/min, weight 60 kg or less, or a strong P-glycoprotein inhibitor); dabigatran 150 mg twice daily (110 mg twice daily if age 80 or over or on verapamil).
• Venous thromboembolism: apixaban 10 mg twice daily for 7 days then 5 mg twice daily; rivaroxaban 15 mg twice daily with food for 21 days then 20 mg once daily with food; dabigatran 150 mg twice daily and edoxaban 60 mg once daily after at least 5 days of parenteral anticoagulation.
• Food: rivaroxaban 15 mg and 20 mg doses are taken with food; apixaban, edoxaban and dabigatran can be taken with or without food. Dabigatran capsules are swallowed whole.

Switching. From warfarin: start apixaban or dabigatran when INR is under 2.0, edoxaban when INR is 2.5 or under, and rivaroxaban when INR is 3.0 or under (for atrial fibrillation) or under 2.5 (for venous thromboembolism). From low molecular weight heparin: start at the time the next dose is due. From an unfractionated heparin infusion: start when the infusion stops.

Missed doses. Twice-daily drugs: take the missed dose if within 6 hours, then continue; otherwise omit it. Once-daily drugs: take the dose the same day, then resume the usual time. Never double.

Interactions. Avoid with strong inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, St John’s wort) and strong dual CYP3A4 and P-glycoprotein inhibitors (itraconazole, ketoconazole, ritonavir and cobicistat-boosted regimens). Dronedarone and verapamil raise dabigatran and edoxaban levels. Avoid combining with non-steroidal anti-inflammatory drugs and limit antiplatelet use.

Kidney impairment. Recalculate clearance before starting and at set intervals; the interval in months equals clearance divided by 10 (for example, 6 months at clearance 60 mL/min).

Older adults and low weight. Use the reduction criteria exactly and do not under-dose outside them.

Special groups. Women of reproductive age need effective contraception. In East Africa, rifampicin-containing tuberculosis regimens and ritonavir-boosted antiretrovirals make most direct oral anticoagulants unsuitable, and warfarin is used.

Monitoring. Creatinine clearance, full blood count and liver tests at 1 month and then every number of months equal to clearance divided by 10 (at least yearly). Check adherence at every visit, because the effect is short.

Referral and escalation. Seek advice for bleeding, new interacting drugs, falling clearance, a procedure, pregnancy and suspected drug failure.

Stopping. Stopping a direct oral anticoagulant removes protection within 24 to 48 hours, so no gap is allowed without a plan. Counsel the patient to carry an alert card.