A study has found that while the severity of ischaemia correlates poorly with daily angina symptoms in patients with stable coronary artery disease (CAD), the development of coronary collateral circulation is associated with both the ischaemic burden and reduced intensity of ischaemic chest pain.¹ This may help explain the often-observed disconnect between stenosis severity and patient-reported symptoms.²

The ORBITA-STAR (Objective Randomized Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina-Systematic Trial of Angina Assessment Prior to Revascularization) was a multicentre, n-of-1, placebo-controlled study.¹ It enrolled 51 participants with severe single-vessel CAD and angina who were referred for percutaneous coronary intervention (PCI).

After stopping antianginal medications, participants documented daily angina symptoms for 14 days using a smartphone app. They then underwent an invasive procedure where baseline Fractional Flow Reserve (FFR) and instantaneous wave-free ratio (iFR) were measured. Each participant was subjected to four 60-second episodes of low-pressure balloon occlusion across their stenosis, each paired in a randomised order with an audiovisually identical placebo inflation. Key endpoints included the Collateral Flow Index (CFI), calculated during balloon occlusion, and a placebo-controlled pain intensity score, rated by patients on a 10-point scale after each episode.

The mean age of participants was 63 years, and 78% were men. The median FFR was 0.68 and the median iFR was 0.80. Daily angina frequency showed little correlation with the severity of ischaemia as assessed by FFR or iFR.

However, an association was found between greater ischaemia (lower FFR and iFR values) and increased collateral flow (higher CFI). Furthermore, a higher CFI was associated with lower placebo-controlled pain intensity scores. The study found no evidence of ischaemic preconditioning, as pain scores and CFI remained stable across the sequential balloon occlusion episodes.

These findings suggest that coronary collateralisation is an adaptive response to chronic ischaemia in patients with single-vessel CAD. This natural bypass circulation appears to have a clinically relevant role in reducing the severity of ischaemic chest pain. The study authors concluded, “Coronary collateralization is associated with ischemic burden and may reduce the intensity of ischemic chest pain. This may explain the nonlinear relationship between stenosis, ischemia, and angina.”¹

The conclusions are limited to a single-vessel disease population. The investigators noted that the more complex associations in patients with multivessel disease are the subject of an ongoing study.

This study was funded by the Medical Research Council, the National Institute for Health and Care Research (NIHR), and the British Heart Foundation.

References

1. Rajkumar CA, Foley MJ, Ahmed-Jushuf F, et al. The Role of the Collateral Circulation in Stable Angina: An Invasive Placebo-Controlled Study. Circulation. 2025;152:1541-1551. https://doi.org/10.1161/CIRCULATIONAHA.125.074687

2. Al-Lamee R, Thompson D, Dehbi H-M, et al; ORBITA investigators. Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial. Lancet. 2018;391:31–40. https://doi.org/10.1016/S0140-6736(17)32714-9

Disclaimer: The information presented in this article is for educational purposes only. Any quotes included reflect the opinions of the individual quoted, and do not necessarily reflect the views of the publisher. The publisher does not guarantee the accuracy or completeness of the content and accepts no responsibility for any errors, or any consequences arising from its use.