Role of Newer Anticoagulants

Direct oral anticoagulants (DOACs) comprise a direct thrombin (factor IIa) inhibitor — dabigatran — and direct factor Xa inhibitors — apixaban, rivaroxaban, and edoxaban.

They act directly on their target enzyme, unlike warfarin (which depletes vitamin K–dependent factors II, VII, IX, X) or heparin (which acts indirectly via antithrombin).

No routine coagulation monitoring and no INR testing.

Rapid onset and offset of action, so no bridging is required.

Predictable dose response, with far fewer food and drug interactions — warfarin is affected by vitamin K–rich foods, alcohol, antibiotics, amiodarone, and many other drugs.

Wider therapeutic window and no need for the frequent dose adjustment that ageing, illness, and renal decline force upon warfarin therapy.

Warfarin dose requirements fall with age — for every 10-year increase in age there is a 15% increase in the risk of an INR ≥5.

A meta-analysis of 12 studies (77,011 patients) showed significantly more effective stroke prevention with a 50% reduction in intracranial bleeding with DOACs compared with warfarin.

DOACs have therefore become the oral anticoagulant of first choice for the majority of patients.

Stroke prevention in non-valvular atrial fibrillation — Class I recommendation, preferred over warfarin.

Treatment of acute DVT and pulmonary embolism, and prevention of recurrence — often without hospital admission.

Prevention of VTE after elective hip or knee replacement, including extended out-of-hospital prophylaxis.

Secondary prophylaxis of VTE at reduced dose.

DOACs are the first choice of anticoagulant for acute VTE in patients without cancer or severe renal insufficiency, mainly because of the lower intracranial bleeding risk versus VKAs.

Dabigatran 150 mg twice daily — requires at least 5 days of initial LMWH/UFH/fondaparinux.

Rivaroxaban 15 mg twice daily for 21 days, then 20 mg once daily — no lead-in parenteral therapy. Extended treatment: consider 10 mg once daily.

Apixaban 10 mg twice daily for 7 days, then 5 mg twice daily — no lead-in. Extended treatment: consider 2.5 mg twice daily.

Edoxaban 60 mg once daily after at least 5 days of parenteral anticoagulation; reduce to 30 mg once daily if creatinine clearance 30–50 ml/min, body weight ≤60 kg, or on strong P-glycoprotein inhibitors.

In patients >75, DOACs as a class were superior to warfarin in both efficacy and safety. Apixaban had the lowest risk of major bleeding, and apixaban, edoxaban and dabigatran had lower rates of intracranial haemorrhage than rivaroxaban or warfarin.

Patients aged ≥75 treated with DOACs for VTE had a significantly lower risk of major bleeding than those on VKAs (relative risk 0.49).

ARISTOPHANES and the PREFER in AF registries confirmed the benefit in the very old, showing lower major bleeding with DOACs even in patients with low body mass index or aged ≥85.

Rivaroxaban and edoxaban are once-daily agents, which may aid adherence. Dabigatran is not suitable for dosette boxes, an important practical point in older people using pill organisers.

DOACs are only equivalent to an INR of 2–3, so warfarin remains mandatory where a higher target is needed: mechanical prosthetic heart valves, moderate-severe mitral stenosis, recurrent thrombosis despite anticoagulation, and some patients with antiphospholipid syndrome.

All DOACs are renally excreted to some extent and undergo some hepatic metabolism — dose reduction is guided by age, weight, renal function and concomitant drugs.

In low body weight patients there is a risk of over-anticoagulation.

Because the half-life is short, missed doses create periods of under-anticoagulation and increased stroke risk — adherence matters more, not less, than with warfarin.

Idarucizumab is a specific monoclonal antibody fragment reversing dabigatran. Andexanet alfa is a modified recombinant factor Xa decoy reversing apixaban and rivaroxaban.

Prothrombin complex concentrate (PCC) is used where specific agents are unavailable — the usual situation in much of India.