FFR Exclusion in ISCHEMIA Trial Control Arm
No, FFR-positive patients were not excluded from the control arm of the ISCHEMIA trial; FFR was used exclusively in the invasive arm to guide revascularization decisions, while the conservative arm received optimal medical therapy without routine catheterization or FFR assessment. 1
FFR Use in ISCHEMIA Trial Design
The ISCHEMIA trial employed a fundamentally asymmetric approach to FFR utilization between treatment arms:
Invasive Strategy Arm
- FFR was used to guide revascularization decisions only in patients randomized to the invasive strategy, ensuring that only functionally significant lesions (FFR ≤0.80) were treated rather than all anatomically visible stenoses 1
- This physiologically-guided approach was part of achieving complete ischemic revascularization using contemporary drug-eluting stents combined with FFR assessment 1
- The FFR threshold of ≤0.80 defined functionally significant stenoses requiring revascularization, consistent with contemporary guidelines 1
Conservative Strategy Arm
- Patients in the conservative arm underwent cardiac catheterization only for failure of optimal medical therapy 2
- There was no routine FFR assessment in the conservative arm because these patients did not undergo routine catheterization 2
- The conservative strategy focused on optimal medical therapy (OMT) including lifestyle advice and pharmacologic interventions 2
Trial Entry Criteria and CCTA Screening
The trial used coronary CT angiography (CCTA) as a "gatekeeper" during randomization to exclude specific anatomic subgroups, not FFR 3, 4:
- Most enrolled participants with normal renal function first underwent blinded CCTA to exclude those with >50% left main stenosis and those without obstructive CAD 2
- Half of screen failures were identified by CCTA, including patients with nonobstructive CAD or unprotected left main CAD 3
- This CCTA screening occurred before randomization, meaning both arms had similar anatomic characteristics at baseline 4
Clinical Implications
The asymmetric FFR use reflects the trial's fundamental design comparing two management philosophies:
- Invasive strategy: Routine catheterization with FFR-guided revascularization plus OMT 1
- Conservative strategy: OMT alone with catheterization reserved for medical therapy failure 2
This design means FFR-positive lesions (FFR ≤0.80) were identified and treated in the invasive arm, while similar lesions in the conservative arm remained unidentified unless patients failed medical therapy and crossed over to catheterization 1, 2.
Evidence Supporting FFR-Guided Approach
The rationale for using FFR in the invasive arm was based on prior evidence showing FFR-guided PCI resulted in significantly lower composite event rates (13.2%) compared to angiography-guided PCI (18.3%, P=0.02) at 1 year, with fewer stents placed (1.9±1.3 vs 2.7±1.2, P<0.001) 1.