The long-term benefits of revascularization over medical therapy for patients with stable coronary artery disease (CAD) remain a subject of clinical debate. New long-term follow-up data from the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) trial provide further insight, demonstrating a sustained benefit for percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) over a median of 11 years.¹
Methodology
The FAME 2 trial was a multicentre, randomised study involving patients with stable CAD and at least one hemodynamically significant stenosis, defined by an FFR value of ≤0.80. For the long-term follow-up, 748 patients from 16 hospitals were included. Participants were randomised to receive either FFR-guided PCI plus medical therapy (n=447) or medical therapy alone (n=441). The primary composite outcome was a hierarchical analysis of time to death, myocardial infarction (MI), or urgent revascularization.¹˒²
Results
At a median follow-up of 11.2 years, the primary composite endpoint occurred in 150 patients (33.6%) in the PCI group compared to 182 patients (41.3%) in the medical therapy group. The analysis resulted in a win ratio of 1.25 in favour of the PCI group (95% CI 1.01–1.56, P=0.043), with a number needed to treat of 17.
The benefit was primarily driven by a significant reduction in urgent revascularizations, which had a win ratio of 4.57 (95% CI 2.53–8.24). The win ratio for MI was 1.50 (95% CI 0.98–2.31), while for all-cause death it was 0.88 (95% CI 0.66–1.17), indicating no significant difference in mortality between the groups.¹
In Practice
These long-term findings from the FAME 2 trial reaffirm that in patients with stable CAD and proven hemodynamically significant stenoses, an initial strategy of FFR-guided PCI reduces the composite risk of death, MI, or urgent revascularization compared to medical therapy alone. The results highlight that the main advantage of this invasive strategy is a substantial and lasting reduction in the need for future urgent revascularization procedures. The data support the continued use of FFR to identify patients with stable CAD who are most likely to benefit from revascularization.
References
1. Collet C, Mahendiran T, Fearon WF, et al. Fractional flow reserve-guided percutaneous coronary intervention versus medical therapy for stable coronary artery disease: long-term results of the FAME 2 trial. Nat Med (2026). https://doi.org/10.1038/s41591-025-04132-5
2. Tonino PAL, De Bruyne B, Pijls NHJ, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360:213–224. https://doi.org/10.1056/NEJMoa0807611
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