FAME 2: FFR-Guided PCI for Stable Coronary Artery Disease
Editor's Note: Commentary based on De Bruyne B, Fearon WF, Pijls NH, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med 2014;371:1208-17.
Revascularization of ischemic coronary stenosis provides symptomatic relief. Although it has been a standard for percutaneous coronary intervention (PCI) decision making, coronary angiography has a limited ability to determine the ischemic significance of intermediate stenoses. Using direct translesional pressure measurements in the cath lab, fractional flow reserve (FFR) identifies lesions that are associated with ischemia. In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, FFR-guided compared to angiographically-guided PCI was superior at one and two years for lower death/myocardial infarction (MI) and MI alone. Historically, the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial found similar outcomes between PCI and medical therapy for stable coronary artery disease (CAD) patients. However, many COURAGE patients did not have significant ischemia. To address the best treatment for ischemic patients with stable CAD, the FAME 2 study compared percutaneous intervention with stenting (PCI) with optimal medical therapy (OMT) to OMT alone with regard to major adverse cardiac events (MACE).
1,220 patients with multivessel CAD with at least one lesion having ischemia demonstrated by FFR <0.80 were randomized to one of the two treatment arms (PCI + OMT vs. OMT alone) and were followed for two years. Endpoints included death from any cause, non-fatal MI, and urgent revascularization.
Patients in the PCI group had a significantly lower primary endpoint than those in the medical therapy group (8% vs. 20%, P <0.001). The reduction of MACE was driven by a lower rate of urgent revascularization (4% vs. 16%, P <0 .001) with no difference in death or MI. Urgent revascularization triggered by MI or ischemic electrocardiographic changes was less frequent in the PCI group (3.4% vs. 7%, P < 0.01). By performing a landmark analysis to exclude the periprocedural troponin elevations in the first week of the index procedure, rates of death and MI from eight days to two years were significantly lower in the PCI group compared to the medical therapy group (4.6% vs. 8.0%, P = 0.04). In patients having no myocardial ischemia (the "registry" group), the rate of the primary endpoint was 9% at two years.
In patients with stable CAD, the FAME 2 study showed that FFR-guided PCI, as compared with medical therapy alone, reduced the MACE rate, and, moreover, when excluding periprocedural myocardial enzyme elevations, PCI with OMT reduced death and MI compared to OMT alone. In contrast, stable CAD patients without ischemia had a favorable outcome with medical therapy alone.
The FAME study demonstrated the superior outcomes of selecting and treating lesions with PCI associated with ischemia (abnormal FFR). The FAME 2 study showed that revascularization of ischemic lesions was better than medical therapy alone with a 10-fold reduction in need for urgent revascularization over two-year follow-up. Compared to "optimal" medical therapy for ischemic heart disease, revascularization by either PCI or coronary artery bypass graft (CABG) is challenged because the survival and rates of MI are not different except for specific clinical settings (three-vessel [3V]/left main [LM] CAD or ST-elevation myocardial infarction [STEMI]). The FAME 2 study supports PCI for ischemic patients and medical therapy for nonischemic patients. Stable nonischemic patients had an annual event rate of 9%. The results of FAME 2 both challenge and support the findings of the COURAGE study because those patients with moderate-to-significant ischemia benefitted by revascularization. Whether the forthcoming National Heart, Lung, and Blood Institute (NHLBI) ISCHEMIA study will provide a final resolution to this controversy remains to be seen.
PCI for most stable patients is not a life-saving event, but, over the long term, provides benefit as demonstrated in the FAME studies and improves quality of life based on studies illustrating symptom improvement with revascularization compared to medical therapy alone in the ischemic CAD individual.
- De Bruyne B, Fearon WF, Pijls NH, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med 2014;371:1208-17.
- Pijls NH, De Bruyne B, Peels K, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med 1996;334:1703-8.
- Tonino PA, Fearon WF, De Bruyne B, et al. Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation. J Am Coll Cardiol 2010;55:2816-21.
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