Targeting the heart of the problem: why coronary inflammation is cardiovascular medicine's next frontier

Despite decades of advances in drug and device development, cardiovascular disease remains the world's leading killer1. Even patients receiving optimal care face sobering statistics: one in five heart attack survivors will experience another event within just two years².

This persistent risk has driven researchers to go back to basics to look at the underlying mechanisms that drive heart attack risk and have led us to a promising new frontier: coronary inflammation.

The inflammation imperative

"All risk factors, from smoking to obesity through to hypercholesterolemia, are driving inflammation in the vasculature, which is ultimately causing rupture of vulnerable plaques,"explains Chris Farina, CEO of Abcentra, in our recent podcast discussion with Fortrea's Cardiovascular and Metabolic Therapeutic Area Head, Dr. Cheerag Shirodaria.

This residual inflammatory risk represents a massive unmet need. In the United States alone, 800,000 patients suffer acute coronary syndrome annually¹, yet current therapies-despite excellent cholesterol and blood pressure control-leave significant risk untreated.

Precision targeting meets diagnostic breakthrough

The next generation of cardiovascular therapies focuses on plaque-targeted approaches that deliver anti-inflammatory effects precisely where inflammation causes harm, rather than suppressing the immune system broadly.

"Rather than inhibit inflammation mechanisms where your body does need these mechanisms to fight off infections, we target inflammation very specifically in the arteries, in the tissue where there is pathology,"Farina explains.

This precision is enabled by breakthrough imaging technology developed by University of Oxford spinout Caristo Diagnostics, where Dr. Shirodaria serves as co-founder and Chief Development Officer. The Fat Attenuation Index (FAI) score can quantify coronary inflammation from routine coronary CT angiograms by detecting phenotypic changes in the adipose tissue surrounding coronary arteries-changes that occur when inflammatory cytokines are released from inflamed vessels. This technology identifies at-risk patients before events occur-even those with seemingly normal arteries³.

Recent published data from the ORFAN registry, involving over 40,000 patients, has revealed that those with the highest inflammation scores face a ten-fold increased risk of cardiovascular death over ten years. Perhaps most striking: approximately 50% of patients could be reclassified for risk using this technology, fundamentally changing their clinical management³.

The clinical development challenge

Bringing these innovations to patients requires navigating complex clinical trial design in uncharted territory. When you're pioneering novel endpoints and patient populations, established playbooks don't exist.

"You need a lot of different expertise to converge on the design,"notes Farina, highlighting Fortrea's role in Abcentra's Phase 2b trial, called FORTIFY, that is evaluating orticumab in post-heart attack patients with residual coronary inflammation⁴.

This collaboration exemplifies the partnership model essential for cardiovascular innovation: combining deep therapeutic area expertise, advanced imaging capabilities, biostatistical sophistication, and operational excellence at specialized sites.

A new era beckons

The convergence of precision therapeutics and diagnostic capabilities promises to reshape cardiovascular medicine. Within five years, we may see the first drugs approved specifically for coronary inflammation, with guidelines embracing inflammation measurement as standard care.

"We stand on the precipice of being able to not only identify these patients-which we can now do using FAI score-but also prescribe treatments that can be effective in reducing their risk,"reflects Dr. Shirodaria.

This vision aligns perfectly with Fortrea's mission: accelerating the development of treatments that transform patient outcomes. By supporting pioneers like Abcentra through complex clinical development journeys, we're helping build the evidence base for tomorrow's breakthroughs.

The path from scientific discovery to patient benefit runs through rigorous clinical trials. As we observe World Heart Day, we're reminded that meaningful progress in heart health depends on the clinical research we conduct today-and the partnerships we forge to make it possible.

Listen to the full podcast discussion between Dr. Cheerag Shirodaria and Chris Farina to explore the science behind coronary inflammation, the development journey of ORTICUMAB, and the role of innovative diagnostics in cardiovascular medicine.

References

• 1. Virani SS, Alonso A, Aparicio HJ, et al. Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation. 2023;147:e93-e621.
• 2. Claessen BE, Guedeney P, Gibson CM, et al. Lipid Management in Patients Presenting With Acute Coronary Syndromes: A Review. J Am Heart Assoc. 2023;12:e018897.
• 3. Chan K, Wahome E, Tsiachristas A, et al. Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study. Lancet. 2024;403(10444):2606-2618.
• 4. Farina M, et al. Inhibition of oxidized low-density lipoprotein with orticumab inhibits coronary inflammation and reduces residual inflammatory risk in psoriasis: A pilot randomized, double-blind placebo-controlled trial. Cardiovascular Research. European Society of Cardiology. 2024;120(7):678-680.