Anticoagulants in geriatric practice — indications and agents

Both the risk of thrombosis and the risk of haemorrhage increase with age. Older patients therefore stand to gain the most from anticoagulation and to lose the most from it — the central tension of geriatric prescribing.

Guidelines are largely extrapolated: patients in landmark trials are on average 5 to 10 years younger than real-world patients, and most trials excluded those with high bleeding risk, renal failure or recent stroke. Consequently guidelines cannot make strong recommendations for people aged 85 and over.

Under-treatment is the bigger problem. Anticoagulation is widely withheld from older patients because of falls, dementia and perceived frailty, despite evidence that these are usually not valid reasons.

Non-valvular atrial fibrillation — long-term stroke prevention (the commonest indication in geriatric practice).

Valvular AF and mechanical prosthetic valves — lifelong warfarin.

Treatment of venous thromboembolism — deep vein thrombosis and pulmonary embolism.

Thromboprophylaxis in medical and surgical inpatients at moderate-to-high risk, and extended prophylaxis after major orthopaedic surgery.

Other: intracardiac thrombus, mitral annular calcification with cerebral embolism, thrombophilia with thrombosis, and antiphospholipid syndrome (warfarin, not a DOAC, in triple-positive disease).

Inhibits vitamin K-dependent synthesis of factors II, VII, IX and X. Efficacy depends on time in therapeutic range. It reduces stroke in AF by about 64% and mortality by about a quarter, and is superior to aspirin (relative risk reduction 39%).

Target INR ranges (Pathy's Table 24.5): 2.0–3.0 for DVT, pulmonary embolism, systemic embolism, mitral stenosis with embolism, TIA and atrial fibrillation; 3.0–4.5 for recurrent DVT/PE despite anticoagulation, arterial disease including myocardial infarction, and mechanical prosthetic heart valves.

Geriatric problems: dose requirement is lower than in younger patients; bleeding risk is increased at both high and normal INRs because of underlying pathology such as peptic ulcer, gastrointestinal malignancy and angiodysplasia; numerous drug interactions; and dietary vitamin K (parsley, broccoli, liver) reduces its effect.

Key interactions (Pathy's Table 29.7): potentiate — amiodarone, simvastatin, fibrates, thyroxine, corticosteroids, cimetidine, omeprazole, chlorpromazine, tricyclics, tamoxifen, aminoglycosides, metronidazole, clarithromycin; reduce — spironolactone, cholestyramine, barbiturates, carbamazepine, rifampicin.

Initiation: use a reduced-dose induction regimen in the elderly (Siguret's regimen: 4 mg daily for three days, then dose by INR). Monitor closely in the first month, when bleeding risk is highest.

Unfractionated heparin potentiates antithrombin; narrow therapeutic range, complex kinetics, wide inter-patient variation. Monitor by APTT ratio 1.5–2. Reversal with protamine sulfate. Risk of heparin-induced thrombocytopenia.

Low-molecular-weight heparin has a longer half-life, better bioavailability and predictable kinetics, allowing once-daily subcutaneous dosing without monitoring. It acts more on factor Xa than thrombin, so it cannot be monitored by APTT — use an anti-Xa assay if monitoring is needed (renal impairment, extremes of weight, pregnancy). LMWH confers a survival advantage in malignancy-associated thrombosis.

Dabigatran (direct thrombin/factor IIa inhibitor); rivaroxaban, apixaban, edoxaban (factor Xa inhibitors). They are broadly equivalent to warfarin at an INR of 2–3, need no routine monitoring, and have far fewer food and drug interactions.

Advantages in the elderly: DOACs are recommended over warfarin in non-valvular AF (Class I) and are first choice for acute VTE in the absence of cancer or severe renal impairment, chiefly because of lower intracranial haemorrhage risk. In patients aged ≥75 the risk of major bleeding is significantly lower with DOACs than with vitamin K antagonists (relative risk about 0.49).

Limitations and cautions: all are renally excreted to some degree and require dose reduction for renal impairment, low body weight and advanced age. DOACs must not be used in mechanical heart valves, moderate-to-severe mitral stenosis, triple-positive antiphospholipid syndrome, or where a target INR above 3 is required. Because of the short half-life, missed doses create periods of under-anticoagulation — a real risk in cognitive impairment. Dabigatran is unsuitable for dosette boxes; rivaroxaban and edoxaban are once daily, which may aid adherence.