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Review
. 2021 Mar 31;10(4):773.
doi: 10.3390/cells10040773.

The Effects of Warfarin and Direct Oral Anticoagulants on Systemic Vascular Calcification: A Review

Kalaimani Elango  1 , Awad Javaid  2 , Banveet K Khetarpal  2 , Sathishkumar Ramalingam  3 , Krishna Prasad Kolandaivel  4 , Kulothungan Gunasekaran  5 , Chowdhury Ahsan  1
Affiliations
Review

The Effects of Warfarin and Direct Oral Anticoagulants on Systemic Vascular Calcification: A Review

Kalaimani Elango et al. Cells. .

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.

Keywords: direct oral anticoagulants; matrix gla protein; valvular calcification; vascular calcification; vitamin K; warfarin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The carboxylated, active form of matrix gla protein prevents vascular calcium formation and relies on the active form of vitamin K. Warfarin inhibits formation of the active form of vitamin K. Inset shows structure of human vitamin K epoxide reductase with warfarin [12]. ucMGP = uncarboxylated matrix gla protein.
Figure 2
Figure 2
Summary figure showing mechanism and implication of warfarin and direct oral anticoagulants (DOACs) on vascular calcification. Warfarin causes calcification due to inhibition of vitamin-K-dependent carboxylation. DOACs may prevent calcification by inhibiting protease-activated receptors (PAR) activation. Gas-6 = growth arrest specific 6 protein; VSMC = vascular smooth muscle cells; MGP = matrix gla protein; BMP = bone morphogenetic protein.
See this image and copyright information in PMC

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