TOPLINE

Supplementation with the vitamin K2 homolog menaquinone-7 for 2 years may reduce the progression of coronary artery calcification (CAC) among patients with symptomatic coronary artery disease. However, the effect was modest, and its clinical significance remains unclear.

METHODOLOGY

• Researchers conducted a phase 3 trial at two hospitals in Netherlands (2012-2024) to evaluate whether supplementation with menaquinone-7 over a period of 2 years attenuated the progression of CAC among patients with symptomatic coronary artery disease.
• A total of 167 patients with concerns suggestive of coronary artery disease and baseline CAC scores between 50 AU and 400 AU were randomly assigned to receive either a once-daily oral tablet of 360 μg of menaquinone-7 (median age 59 years) or an identical placebo (median age, 61 years). Overall, 42% of the participants were women.
• Participants underwent CT scanning at baseline, 1 year, and 2 years to measure the extent of coronary calcification, assessed using the CAC score and calcium mass.
• The primary outcome was the evolution of the CAC score and calcium mass at 1 and 2 years of follow-up; secondary outcomes included the incidence of new calcifications.

TAKEAWAY

• The median CAC score increased from 135 AU at baseline to 184 AU at 2 years in the supplementation group and from 145 AU at baseline to 214 AU at 2 years in the placebo group, corresponding to a significant difference between the groups (P = .02).
• In a separate analysis, treatment with menaquinone-7 was associated with a 19-unit reduction in the yearly increase in the CAC score (P < .001). The percentage of fast progressors, however, was not significantly different between the groups.
• Similar results were observed for calcium mass, which increased from 25 mg at baseline to 32 mg at 2 years in the supplementation group and from 26 mg at baseline to 38 mg at 2 years in the placebo group, translating into a significant between-group difference (P = .01).
• At baseline, all patients had coronary plaques, which caused mild stenosis in most patients and affected three segments. Over time, the severity of stenosis and vessel involvement increased similarly in both groups. Additionally, the incidence of adverse effects of the treatment was remarkably low.

IN PRACTICE

“The overall effect is modest, and given that the percentage of fast progressors did not differ between the 2 treatment groups, the clinical significance of our findings remains to be demonstrated. It is uncertain, for instance, whether the relatively small reduction in the evolution of the CAC score translates into a reduction of cardiovascular events,” the authors wrote.

SOURCE

The study was led by Liv M. Vossen, MD, PhD, Department of Medicine, Maastricht University Medical Center, Maastricht, Netherlands. It was published online on June 10 in JAMA Cardiology.

LIMITATIONS 

The authors could not assess the presence of microcalcifications. The study had a relatively small sample size, and the high number of patients who refused to participate raised concerns about the generalizability of the results. Moreover, the dietary intake of vitamin K-rich foods among the participants was not monitored.

DISCLOSURES

This study was supported by the Dutch Heart Foundation. One author disclosed receiving grants from and holding shares in pharmaceutical companies outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.