FORTIFY: a phase 2b randomised trial evaluating the effect of orticumab on coronary inflammation (FAI-Score) in post myocardial infarction patients selects for patients with high residual FAI-Score

Background

Residual coronary inflammation remains a driver of recurrent cardiovascular risk after myocardial infarction (MI), even in clinically stable patients receiving guideline-directed secondary prevention. The Fat Attenuation Index (FAI)-Score, derived from coronary computed tomographic angiography (CCTA), noninvasive measures local coronary inflammation associated with major adverse cardiovascular events. In a phase 2a pilot study, orticumab reduced coronary inflammation in patients with a high baseline FAI-Score. FORTIFY is a randomised clinical trial that aims to enroll patients with elevated FAI-Score after MI despite well-controlled risk factors. FORTIFY will test whether the monoclonal antibody orticumab reduces local inflammation.

Methods

FORTIFY is an ongoing, multicenter, randomised, double-blind, placebo-controlled, phase 2b trial of orticumab in clinically stable patients >6 months after type 1 MI. Participants must be on guideline-directed secondary prevention with well-controlled LDL-C, blood pressure, and glycemia. The entry criteria include elevated coronary inflammation defined as FAI-Score ≥75th centile in at least 1 coronary artery or ≥50th centile in at least 2 arteries. Eligible participants are randomised 2:2:1:1 to high-dose orticumab, low-dose orticumab, or matched placebo regimens. Follow-up CCTA is performed at 6 months. The primary endpoint is percent change from baseline in mean FAI-Score across the 3 major coronary arteries.

Results of screening by FAI

As of 25 February 2026, 185 participants underwent screening CCTA with FAI-Score assessment; 97 were eligible and 88 were not eligible for randomisation. In this clinically stable population >6 months after type 1 MI, FAI-Score centiles showed broad distribution in LAD, LCx, RCA, and the mean, providing the first description of FAI-Score centile distribution in a stable post-MI trial population. Across all screened participants, values spanned nearly the full 0–100 scale. LAD FAI-Score centiles ranged from 1% to 99% (mean 49.9%, SD 29.4). In the LAD, FAI score in eligible participants (n=97) ranged from 12% to 99% (mean 70.7%, SD 18.8), versus 1% to 72% (mean 26.5%, SD 20.0) in non-eligible participants (n=86). Similar patterns were observed for LCx and RCA.

Conclusions

These findings support the feasibility of use of FAI score as an enrichment strategy for residual coronary inflammation and support the choice of studying a stable population >6 months post-MI, where substantial coronary inflammation persists despite contemporary secondary prevention.FAI Score centile distribution