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Evevident
Original paper
2012NEJMCardiology

FAME 2

Fractional Flow Reserve-Guided PCI versus Medical Therapy in Stable Coronary Disease

RCTStable CAD / physiology-guided PCI

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Overview

In stable CAD with FFR-positive lesions, PCI plus medical therapy reduced urgent revascularization more than death or MI.

Clinical takeaway

FAME 2 refined stable-CAD teaching by showing that physiologically significant stenoses are more PCI-relevant, while making clear that the early primary endpoint benefit was driven mainly by urgent revascularization.

Key result

Primary endpoint: 4.3% with FFR-guided PCI vs 12.7% with medical therapy; HR 0.32, driven by urgent revascularization.

Practice impact

Use physiology to identify stable lesions where PCI is more likely to reduce symptoms or urgent revascularization risk.

Evidence

Study design

Randomized, open-label, controlled trial with a parallel registry; stopped early.

Enrollment

888

Follow-up

Mean 7 months at early termination; later extended to 5 years.

Geography

Multinational

Clinical question

Does FFR-guided PCI improve outcomes compared with medical therapy alone in stable CAD with physiologically significant stenoses?

Population

  • Patients with stable coronary artery disease and at least one stenosis with FFR of 0.80 or less.

Intervention

FFR-guided PCI with drug-eluting stents plus best available medical therapy.

Comparator

Best available medical therapy alone.

Primary outcome

Composite of death, myocardial infarction, or urgent revascularization.

FFR-guided PCI plus medical therapy reduced the composite endpoint, mainly by reducing urgent revascularization.

Hazard ratio / 0.32 / CI 95% CI 0.19-0.53 / p=<0.001

Key results

  • Primary endpoint: 4.3% with PCI vs 12.7% with medical therapy; HR 0.32; 95% CI 0.19-0.53; p<0.001.
  • Urgent revascularization: 1.6% with PCI vs 11.1% with medical therapy; HR 0.13; 95% CI 0.06-0.30; p<0.001.
  • Patients without ischemia by FFR entered a registry and had favorable outcomes with medical therapy.

Harms

  • PCI carries periprocedural myocardial infarction risk; death and MI alone did not differ significantly between groups.
  • Adenosine used for FFR can cause transient dyspnea, flushing, or heart block.

Clinical Use

When to cite

  • When discussing FFR-positive lesions and why physiology can select PCI candidates.

Practice impact

  • Supports physiology-guided selection for PCI in stable CAD rather than anatomy alone.

Applicability

  • Most applicable to stable CAD patients with FFR-positive stenoses where PCI is being considered.

Limitations

  • Stopped early for benefit, which can exaggerate effect-size estimates.
  • Open-label design can influence revascularization decisions.
  • Primary benefit was largely urgent revascularization rather than death or MI.

Common misinterpretations

  • Do not cite FAME 2 as showing a broad mortality benefit for PCI in stable CAD.

Related evidence

FAME - Earlier TrialCOURAGE - ContextISCHEMIA - Context

Citation

De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367(11):991-1001. doi:10.1056/NEJMoa1205361

The difference was driven by a lower rate of urgent revascularization.