Abstract

Warfarin has been utilized for decades as an effective anticoagulant in patients with a history of strong risk factors for venous thromboembolism (VTE). Established adverse effects include bleeding, skin necrosis, teratogenicity during pregnancy, cholesterol embolization, and nephropathy. One of the lesser-known long-term side effects of warfarin is an increase in systemic arterial calcification. This is significant due to the association between vascular calcification and cardiovascular morbidity and mortality. Direct oral anticoagulants (DOACs) have gained prominence in recent years, as they require less frequent monitoring and have a superior side effect profile to warfarin, specifically in relation to major bleeding. The cost and lack of data for DOACs in some disease processes have precluded universal use. Within the last four years, retrospective cohort studies, observational studies, and randomized trials have shown, through different imaging modalities, that multiple DOACs are associated with slower progression of vascular calcification than warfarin. This review highlights the pathophysiology and mechanisms behind vascular calcification due to warfarin and compares the effect of warfarin and DOACs on systemic vasculature.

Highlights

  • Anticoagulants are an effective tool to reduce morbidity and mortality in patients suffering from arterial thromboembolism and venous thromboembolism

  • Bone gla protein, periostin, gla-rich protein, and growth-arrest specific protein 6 may all depend on vitamin K carboxylation, and their inhibition by warfarin may be linked to vascular calcification [45]

  • As direct oral anticoagulants (DOACs) have no interaction with vitamin K, they presumably would not increase the rate of vascular calcification in patients

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Summary

Introduction

Anticoagulants are an effective tool to reduce morbidity and mortality in patients suffering from arterial thromboembolism and venous thromboembolism. Millions of patients are on lifelong anticoagulant therapy for various indications. Since the 1960s, warfarin has been used effectively to prevent thromboembolism. During the last 10 years, direct oral anticoagulants (DOACs) have gained prominence due to their preferable side-effect profile and ease of use. Due to the cost and relatively recent approval of DOACs, warfarin is more affordable and still has a broader range of indications. Prescription trends are showing that warfarin use continues to decline, while DOAC use is on the rise [2,3]. This review analyzes the mechanisms which promote calcification in warfarin users and examines the effects of DOACs and warfarin on systemic vasculature

History
Mechanism of Action and Properties
Advantages and Disadvantages of Warfarin and Direct Oral Anticoagulants
Vascular Calcification
Pathophysiology of Vascular Calcification
The Role of Vitamin K
Impact of Matrix Gla Protein
Other Mechanisms
Mechanisms by Which Direct Oral Anticoagulants May Prevent Vascular
Studies Linking Warfarin to Calcification
Findings
Study Design
10. Effects of Warfarin and Direct Oral Anticoagulants on Valvular Calcification
11. Considerations in Patients with Kidney Disease
12. Conclusions
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