anticoagulants

DOACs have replaced warfarin for most indications (AF, VTE) with more predictable pharmacology and lower ICH risk. Warfarin remains mandatory for mechanical heart valves. Heparins (UFH, LMWH) are the parenteral backbone for acute anticoagulation. Apixaban has the most favourable bleeding profile among DOACs — now confirmed head-to-head vs rivaroxaban in COBRRA (2026).

classes

Class	Target	Route	Details
warfarin	vitamin K–dependent factors (II, VII, IX, X)	oral	mandatory for mechanical valves; INR monitoring
[[doacs	DOACs]]	direct factor Xa (apixaban, rivaroxaban, edoxaban) or IIa (dabigatran)	oral
[[heparins	UFH]]	antithrombin-mediated IIa + Xa	IV / SC
[[heparins	LMWH]] (enoxaparin, dalteparin)	antithrombin-mediated, predominantly anti-Xa	SC
[[heparins	fondaparinux]]	selective anti-Xa via antithrombin	SC

selection

Non-valvular AF / VTE → DOACs (apixaban preferred — ARISTOTLE (2011), COBRRA (2026))
Mechanical heart valves → warfarin (DOACs contraindicated)
ACS with planned PCI → UFH
Haemodynamic instability / severe CKD → UFH
VTE in pregnancy → LMWH
VTE in cancer → DOACs or LMWH (dalteparin)
Stable CAD/PAD → consider low-dose rivaroxaban 2.5 mg BID + ASA (COMPASS)

reversal — quick reference

Agent	Reversal
warfarin	vitamin K ± 4-factor PCC
apixaban / rivaroxaban / edoxaban	andexanet alfa; PCC if unavailable
dabigatran	idarucizumab 5 g IV
UFH	protamine
LMWH	protamine (partial ~60%)
fondaparinux	no specific agent; consider rFVIIa

emerging therapy — factor XI inhibitors

factor XI inhibitors — pipeline —

Weitz, Nat Rev Cardiol. 2025 FXI inhibitors aim to separate thrombosis protection from bleeding risk. Promising phase II data (abelacimab: 67% reduction in major/CRNM bleeding vs rivaroxaban in AF), but multiple phase III setbacks — asundexian inferior to apixaban in AF (OCEANIC-AF stopped), milvexian futility in ACS (LIBREXIA-ACS stopped). Abelacimab (LILAC-AF) and milvexian (LIBREXIA-AF) trials ongoing. Not yet available for clinical use.