Associations of VICTORION-1 PREVENT eligibility with subclinical cardiovascular and inflammatory damage in a European...

The VICTORION-1 PREVENT (V-1P) trial is evaluating the efficacy of inclisiran versus placebo on cardiovascular events in primary prevention patients at high-risk for ASCVD. We assessed whether V-1P eligibility, based on Pooled Cohort Equations (PCE) and Predicting Risk of Cardiovascular Disease Events (PREVENT) equations, was associated with subclinical cardiovascular and inflammatory abnormalities in a healthy European population.

We included individuals from the STANISLAS cohort in France aged 40-79 years, LDL-C 70-189 mg/dL and without ASCVD or liver disease. Participants were categorized as V-1P eligible using 10-year ASCVD risk using PCE and PREVENT. Associations with vascular, echocardiographic, and biomarkers were assessed using age- and sex-adjusted linear regression.

Among 848 participants (mean age 60 years, 51% female), 16% were eligible per PCE, of which 7% were also eligible with PREVENT. Only one participant was eligible by PREVENT alone. Compared with non-eligible participants, V-1P-eligible individuals, whether by PCE alone or PCE and PREVENT, displayed significant subclinical abnormalities. Compared with V-1P ineligible participants, V-1P eligible participants had increased intima media thickness (+51 µm, p < 0.009 for PCE+PREVENT) and increased mean pulse wave velocity (+0.89 m/s, p < 0.001 for both PCE and PCE+PREVENT) on vascular ultrasound. V-1P eligible participants by PCE+PREVENT also showed signs of subclinical myocardial injury and inflammation, with a 1.3 fold higher troponin (p = 0.015), 1.6-fold higher interleukin-6 (p < 0.001) and a 2-fold higher high sensitivity C-reactive protein (p < 0.001).

A large proportion of asymptomatic individuals without known cardiovascular disease would be eligible for the V-1P trial based on both PCE and PREVENT equations. V-1P eligible participants had evidence of subclinical cardiovascular and inflammatory abnormalities.