Study Confirms Warfarin’s Dangerous Health Impact in Men

The most common treatment for poor blood flow is to prescribe a vitamin K antagonist, such as warfarin. This anticoagulant interferes with K activity in the liver, resulting in the blood’s inability to form an undesired blood clot. However, it is recognized that this activity not only impedes coagulation, but also other K-dependent proteins that support bones and cardiovascular health, such as Matrix Gla Protein (MGP).

MGP is a vitamin K-dependent protein that is considered the one of the greatest modulators of arterial calcification, a common cardiovascular disease associated with poorer health outcomes. The role of MGP has raised concerns about possible effects of warfarin on vascular calcification in humans. Researchers Han and O’Neill recently demonstrated a 50% increase in prevalence that was independent of other cardiovascular risk factors in a large cohort of women with current or past warfarin use. To that end, they embarked on a new study designed to test the hypothesis that use of warfarin is associated with increased arterial calcification in the lower extremities and in men.

To demonstrate that the results are generalizable to other arteries and to men, researchers performed a similar study of arterial calcification in lower extremities detected on standard radiographs. This retrospective-matched, cohort study assessed 430 patients with radiographs performed during or after warfarin therapy. Each patient was matched to a patient without warfarin exposure based on age, sex, and diabetes status. Radiographs were reviewed visually for arterial calcification.

The results demonstrated a greater prevalence of peripheral arterial calcification in patients receiving warfarin. These results proved that the association of warfarin use with vascular calcification is present in men as well as women. The effect of warfarin was similar to the 50% increase observed previously in breast arterial calcification and was dependent on duration, with only durations of >5 years showing an increased prevalence of peripheral arterial calcification. The prevalence of arterial calcification was much lower in patients aged 60 years.

The researchers concluded, “Warfarin use is associated with lower extremity arterial calcification in both men and women independent of age, sex, diabetes status, and other patient characteristics. This may have implications for the choice of therapies for long-term anticoagulation.”

“While oral anticoagulants like warfarin have been prescribed for years, the effect they have on other K-dependent proteins represents an increasing concern,” says Katarzyna Maresz, president of the International Science and Health Foundation. “But the standard of care is changing with the development of a new class of oral anticoagulants that are not vitamin K antagonists and relatively devoid of major safety considerations, expanding treatment options and allowing patients to continue supporting their bone and cardiovascular health with vitamin K2 supplementation. While this new class of oral anticoagulants are not available in every country yet, they do present a positive development that is eagerly anticipated.”


Han KH, O’Neill WC. Increased Peripheral Arterial Calcification in Patients Receiving Warfarin. J Am Heart Assoc. 2016;5:e002665 doi: 10.1161/JAHA.115.002665.


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