Doppler Ultrasound Monitoring of Echogenicity in Asymptomatic Subcritical Carotid Stenosis and Assessment of Response to Oral Supplementation of Vitamin K2 (PLAK2 Randomized Controlled Trial)

Background: Plaque composition may predict the evolution of carotid artery stenosis rather than its sole extent. The grey scale median (GSM) value is a reproducible and standardized value to report plaque echogenicity as an indirect measure of its composition. We monitored plaque composition in asymptomatic subcritical carotid stenosis and evaluated the effect of an oral modulating calcification factor (vitamin K2). Methods: Carotid plaque composition was assessed by GSM value. Monitoring the effects of standard therapy (acetylsalicylic acid and low-medium dosage statin) (acetylsalicylic acid (ASA) arm) or standard therapy plus vitamins K2 oral supplementation (ASA + K2 arm) over a 12 months period was conducted using an ultrasound scan in a prospective, open-label, randomized controlled trial (PLAK2). Results: Sixty patients on low-medium dosage statin therapy were enrolled and randomized (30 per arm) to either ASA + K2 or ASA alone. Thirty-seven patients (61.6%) showed at 12 months a stable plaque with a mean increase in the GSM value in respect to the baseline of 2.6% with no differences between the two study arms (p = 0.66). Fifteen patients (25%) showed an 8% GSM value reduction respect the baseline with no differences between the two study arms (p = 0.99). At multivariable analysis, the adjusted mean (95% confidence interval) GSM change per month from baseline was greater in the ASA + K2 arm (-0.55 points, p = 0.048) compared to ASA alone (-0.18 points, p = 0.529). Conclusions: Carotid plaque composition monitoring through GSM value represents a laborious procedure. Although its use may not be applied to everyday practice, a specific application consists in evaluating the effect of pharmacological therapy on plaque composition. This 12 months randomized trial showed that the majority of subcritical asymptomatic carotid plaque on treatment with low-medium dosage statin presented a stable or increased echogenicity. Although vitamin K2 beyond standard therapy did not determine a significant change in plaque composition, for those who presented with GSM reduction it did enhance a GSM monthly decline.