Determining the Physiological Threshold for Angina (ORBITA-FIRE): A Double-Blind, Randomized, Placebo-Controlled Study
Authors' conclusion
Physiological thresholds for angina, FFRangina and RFRangina, are highly individualized, vary with cardiac workload, and are consistently lower than the universal ischemia-based thresholds used to guide revascularization.
Study context
- Population
- Patients with stable angina and single-vessel CAD after imaging-guided percutaneous coronary intervention (PCI)
- Participants
- 65 patients
- Comparison
- In-stent balloon inflation vs placebo inflation at rest and during low- and high-intensity exercise
- Primary endpoint
- FFRangina and RFRangina at symptom onset (physiological thresholds for angina)
Methodological detailsmulticentre, double-blind, placebo-controlled
- Multicentre
- Double-blind
- Placebo-controlled
Primary result
As reported in the abstract
Physiological thresholds for angina
| Group | Value | FFRangina | RFRangina |
|---|---|---|---|
| Rest | median 0.29 (IQR 0.23–0.35) | 0.29 (IQR, 0.23-0.35) | 0.22 (IQR, 0.16-0.30) |
| Low-intensity exercise | median 0.38 (IQR 0.30–0.48) | 0.38 (IQR, 0.30-0.48) | 0.26 (IQR, 0.18-0.36) |
| High-intensity exercise | median 0.45 (IQR 0.36–0.55) | 0.45 (IQR, 0.36-0.55) | 0.32 (IQR, 0.23-0.46) |
Value
Restmedian 0.29 (IQR 0.23–0.35)
Low-intensity exercisemedian 0.38 (IQR 0.30–0.48)
High-intensity exercisemedian 0.45 (IQR 0.36–0.55)
FFRangina
Rest0.29 (IQR, 0.23-0.35)
Low-intensity exercise0.38 (IQR, 0.30-0.48)
High-intensity exercise0.45 (IQR, 0.36-0.55)
RFRangina
Rest0.22 (IQR, 0.16-0.30)
Low-intensity exercise0.26 (IQR, 0.18-0.36)
High-intensity exercise0.32 (IQR, 0.23-0.46)
- All thresholds significantly lower than clinical diagnostic cut points
- P < 0.001
Further findings
Pre-PCI physiology
- Median pre-PCI fractional flow reserve (FFR)
- 0.59 (IQR, 0.46-0.70)
- Median pre-PCI RFR
- 0.61 (IQR, 0.40-0.82)
Symptom reproducibility by threshold (rest, low-, high-intensity exercise)
- Lower FFRangina associated with greater symptom reproducibility
- P = 0.008, P<0.001, P<0.001
- Lower RFRangina associated with greater symptom reproducibility
- P = 0.015, P<0.001, P=0.002
Baseline angina burden and symptom relief with PCI
- Lower angina thresholds predicted higher baseline angina burden and greater symptom relief with PCI
- probability of interaction >0.999
Original publication
Determining the Physiological Threshold for Angina (ORBITA-FIRE): A Double-Blind, Randomized, Placebo-Controlled Study. Circulation. Published 8 May 2026. doi:10.
Summarised from the published abstract; every number is checked against it