Warfarin After Seven Decades: Persistent Value and the Contemporary Role of Vitamin K Antagonism
7 affiliations
- 1Department of Medicine, Hypertensive Heart Disease and Anticoagulation Sectors, Paulista School of Medicine, Federal University of Sao Paulo, Brazil
- 2Department of Medicine, Coronary Artery Disease and Anticoagulation Sectors, Paulista School of Medicine, Federal University of Sao Paulo, Brazil
- 3Department of Medicine, Hypertensive Heart Disease Sector, Paulista School of Medicine, Federal University of Sao Paulo, Brazil
- 4Department of Medicine, Cardiomyopathy and Heart Transplant Sectors, Paulista School of Medicine, Federal University of Sao Paulo, Brazil
- 5Department of Medicine, Valvular Heart Disease and Echocardiography Sectors, Paulista School of Medicine, Federal University of Sao Paulo, Brazil
- 6Department of Medicine, Electrocardiography Sector, Paulista School of Medicine, Federal University of Sao Paulo, Brazil
- 7Department of Medicine, Coronary Artery Disease Sector, Heart Institute, Medicine School, University of Sao Paulo, Brazil
Abstract
Warfarin is one of the most enduring drugs in cardiovascular medicine. Although direct oral anticoagulants (DOACs) have transformed anticoagulation, especially in atrial fibrillation (AF) eligible for DOAC therapy, their success cannot be extrapolated to every thrombotic substrate. This review examines the contemporary boundaries of warfarin and vitamin K antagonist (VKA) therapy. Mechanical heart valves remain the clearest setting in which lifelong international normalized ratio (INR)-guided VKA therapy is required; randomized attempts to substitute dabigatran or apixaban have failed. In rheumatic heart disease-associated AF, INVICTUS favored VKA therapy over rivaroxaban, supporting the VKA class rather than warfarin specifically. High-risk thrombotic antiphospholipid syndrome, particularly triple-positive disease, is another VKA-preferred setting. Left ventricular thrombus (LVT) occupies an evolving position in which warfarin remains established, while randomized evidence supports rivaroxaban as a potential alternative in selected acute post-myocardial infarction LVT. Pregnancy with mechanical valves requires dynamic maternal–fetal risk balancing, whereas advanced chronic kidney disease and dialysis represent areas of uncertainty rather than intrinsic indications for warfarin. The global relevance of warfarin also depends on total anticoagulation burden, including INR monitoring, travel, treatment continuity, quality of anticoagulation, and reversal capacity. The persistence of VKA efficacy in selected highly thrombogenic environments raises a biologically plausible hypothesis that broader suppression of vitamin K-dependent factors may matter, but this mechanism is not established by clinical trials. Contemporary anticoagulation should therefore be substrate-centered: VKA therapy remains necessary in some conditions, preferred in others, increasingly replaceable in several, and uncertain in a few.
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BibTeX
@article{leite2026warfarin,
title = {{Warfarin After Seven Decades: Persistent Value and the Contemporary Role of Vitamin K Antagonism}},
author = {Weverton Ferreira Leite and Wilma Noia Ribeiro and Rui Manuel dos Santos Povoa and Dirceu Rodrigues de Almeida and Daniela Fernanda Alli Hemerly and Braulio Luna Filho and Valdir Ambrosio Moises and Jose Antonio Franchini Ramires},
journal = {Cardiology research},
year = {2026},
month = oct,
doi = {10.14740/cr2322},
url = {https://europepmc.org/article/PMC/PMC13719647},
note = {CC BY},
}
RIS
TY - JOUR
TI - Warfarin After Seven Decades: Persistent Value and the Contemporary Role of Vitamin K Antagonism
AU - Weverton Ferreira Leite
AU - Wilma Noia Ribeiro
AU - Rui Manuel dos Santos Povoa
AU - Dirceu Rodrigues de Almeida
AU - Daniela Fernanda Alli Hemerly
AU - Braulio Luna Filho
AU - Valdir Ambrosio Moises
AU - Jose Antonio Franchini Ramires
PY - 2026
DA - 2026/10/24
JO - Cardiology research
DO - 10.14740/cr2322
UR - https://europepmc.org/article/PMC/PMC13719647
AB - Warfarin is one of the most enduring drugs in cardiovascular medicine. Although direct oral anticoagulants (DOACs) have transformed anticoagulation, especially in atrial fibrillation (AF) eligible for DOAC therapy, their success cannot be extrapolated to every thrombotic substrate. This review examines the contemporary boundaries of warfarin and vitamin K antagonist (VKA) therapy. Mechanical heart valves remain the clearest setting in which lifelong international normalized ratio (INR)-guided VKA therapy is required; randomized attempts to substitute dabigatran or apixaban have failed. In rheumatic heart disease-associated AF, INVICTUS favored VKA therapy over rivaroxaban, supporting the VKA class rather than warfarin specifically. High-risk thrombotic antiphospholipid syndrome, particularly triple-positive disease, is another VKA-preferred setting. Left ventricular thrombus (LVT) occupies an evolving position in which warfarin remains established, while randomized evidence supports rivaroxaban as a potential alternative in selected acute post-myocardial infarction LVT. Pregnancy with mechanical valves requires dynamic maternal–fetal risk balancing, whereas advanced chronic kidney disease and dialysis represent areas of uncertainty rather than intrinsic indications for warfarin. The global relevance of warfarin also depends on total anticoagulation burden, including INR monitoring, travel, treatment continuity, quality of anticoagulation, and reversal capacity. The persistence of VKA efficacy in selected highly thrombogenic environments raises a biologically plausible hypothesis that broader suppression of vitamin K-dependent factors may matter, but this mechanism is not established by clinical trials. Contemporary anticoagulation should therefore be substrate-centered: VKA therapy remains necessary in some conditions, preferred in others, increasingly replaceable in several, and uncertain in a few.
SN - 1923-2829
SN - 1923-2837
ER -