Supplementation with the vitamin K homologue menaquinone-7 (MK-7) significantly attenuated coronary artery calcification (CAC) compared with placebo in adults with symptomatic coronary artery disease (CAD), according to research published June 10 in JAMA Cardiology.

The VitaK-CAC trial randomized 167 symptomatic patients (median age, 59-61; 42% women; 78% receiving statins) with symptomatic CAD and a CAC of 50-400 Agatston units (AU) 1:1 to two years of daily oral MK-7 360 µg or placebo. All patients had visible coronary plaques at baseline, but none had high-risk plaque. The trial had 80% adherence with a 17% dropout rate; 75 participants in each arm completed the entire follow-up period.

During the trial, the treatment arm saw an increase in MK-7 plasma levels from a median of 0.50 µg/L to 6.56 µg/L (p<0.001).

Results showed a significant between-group difference in the increase in CAC scores from baseline. In the placebo arm, CAC increased from 145 AU to 173 AU at one year and 214 at two years, compared with the active treatment group increasing from 135 AU at baseline to 150 AU at one year and 184 at two years (p=0.02).

Baseline CAC score and treatment group were associated with changes in CAC score, and increase in yearly CAC score was reduced with treatment by 19 units.

In secondary endpoints, CAC score correlated with the number of noncalcified plaques that became partially calcified during the study (p=0.04), but not with other types.

Investigators Liv M. Vossen, MD, PhD, et al., call MK-7's effect modest and raise questions of possible calcification-promoting effects. However, "CAC remains a powerful predictor of major cardiovascular events," they write. "Thus, before dismissing MK-7 as a form of treatment with a potentially adverse outcome, we need more information on the effects of this vitamin on hard endpoints."

Michael J. Blaha, MD, MPH, and Sungwoo Choi, MD, MPH, call the results "intriguing" in an accompanying editorial comment, yet raise questions regarding their clinical significance. They call for future trials "with larger sample sizes, longer follow-up, innovative CT imaging (e.g., artificial intelligence-based calcium-omics), and complementary imaging modalities (e.g., fluorine 18–labeled sodium fluoride positron emission tomography imaging) that can capture microcalcifications to better quantify any potential clinical benefits of MK-7."