FAME-2 Trial Design: FFR-Positive Patients in the Control Arm
Yes, FFR-positive patients (FFR ≤0.80) were included in the control arm (optimal medical therapy alone without PCI) in the FAME-2 trial. 1
Trial Design Structure
The FAME-2 trial enrolled 1220 patients with stable coronary artery disease and angiographically significant stenoses. 1, 2, 3 The study design specifically:
Identified 888 patients with at least one functionally significant stenosis (FFR ≤0.80) who were then randomized to either FFR-guided PCI plus optimal medical therapy OR optimal medical therapy alone. 1, 2, 3
Randomized these FFR-positive patients (FFR ≤0.80) in a 1:1 ratio to the two treatment arms, meaning approximately 441-447 patients with hemodynamically significant stenoses were assigned to the medical therapy-only control arm. 2, 3
Created a separate registry for the 332 patients in whom all stenoses had FFR >0.80, who received medical therapy but were not part of the randomized comparison. 1, 2, 3
Critical Design Feature
The control arm specifically consisted of patients with proven ischemic lesions (FFR ≤0.80) who did not receive PCI. 1 This was an unblinded design where both participants and clinicians were aware that PCI had been cancelled by protocol despite the presence of functionally significant stenoses. 1
Clinical Outcomes in FFR-Positive Control Patients
At 5-year follow-up, patients with FFR ≤0.80 randomized to medical therapy alone (the control arm) experienced:
Primary endpoint rate of 27.0% (death, myocardial infarction, or urgent revascularization) compared to 13.9% in the PCI group (hazard ratio 0.46,95% CI 0.34-0.63, P<0.001). 2
Urgent revascularization rate of 21.1% compared to 6.3% in the PCI group (hazard ratio 0.27,95% CI 0.18-0.41), which drove the difference in the primary endpoint. 2
No significant difference in death rates (5.2% vs 5.1%) or myocardial infarction rates (12.0% vs 8.1%) between medical therapy and PCI groups. 2
Important Clinical Context
The trial was stopped prematurely by the Data Safety Monitoring Board due to statistically significant reduction in urgent revascularization in the PCI group, highlighting the clinical consequences of leaving FFR-positive lesions untreated. 1
Cardiologists blinded to treatment assignment adjudicated the urgent revascularization outcomes, which required both urgent unplanned hospital admission with persistent/increasing symptoms AND revascularization performed within 24 hours of admission. 1