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Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) Trial
Study type	randomized controlled trial
Dates	enrollment January 2006 through September 2007
Locations	20 centers in the US and Europe
Published	2009
Article	Tonino, Pim A.L.; et al. (15 January 2009). "Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention". New England Journal of Medicine. 360 (3): 213–224. doi:10.1056/NEJMoa0807611.

The Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) Trial was a landmark clinical study that assessed the efficacy and safety of using fractional flow reserve (FFR) to guide percutaneous coronary intervention (PCI) in patients with multivessel coronary artery disease. The trial's findings have significantly influenced clinical practice and guidelines in cardiology.

Background

Identifying which lesions should be revascularized is crucial for improving outcomes in patients with multivessel coronary artery disease. Traditional angiography often fails to accurately assess the functional significance of coronary stenoses. Fractional flow reserve (FFR) is an invasive measurement that determines the physiological impact of coronary stenosis on myocardial blood flow.

Study design

The FAME trial was a prospective, multicenter, randomized controlled trial conducted across several international centers. It compared two strategies for guiding PCI in patients with multivessel coronary artery disease:

• Angiography-Guided PCI: Revascularization based solely on the angiographic severity of coronary lesions.
• FFR-Guided PCI: Revascularization guided by FFR measurements, with PCI performed only on lesions with an FFR ≤ 0.80, indicating hemodynamic significance.

The trial's primary endpoint was a composite of major adverse cardiac events (MACE) at one year. MACE includes death, myocardial infarction, and repeat revascularization. The secondary endpoints included procedure time, amount of IV contrast agent used, function class at one year, health-related quality of life, the number of anti-anginal medications used, overall cost-effectiveness, and individual MACE components at 30 days, six months, and one year.

Key findings

The FAME trial demonstrated several key findings:

• Reduction in MACE: Patients in the FFR-guided group experienced a significantly lower rate of MACE at one year compared to the angiography-guided group (13.2% vs. 18.3%).
• Fewer Stents Used: The FFR-guided strategy resulted in fewer stents implanted, reducing the potential for stent-related complications.
• Cost-Effectiveness: FFR-guided PCI was more cost-effective, with reduced procedure times and material costs.

Clinical implications

The results of the FAME trial have had a profound impact on clinical practice:

• Guideline Changes: International cardiology guidelines now recommend using FFR to guide revascularization decisions in patients with multivessel coronary artery disease.
• Improved Patient Outcomes: The adoption of FFR-guided PCI has been associated with better patient outcomes, including lower rates of death, myocardial infarction, and repeat revascularization.

Follow-up studies

Following the success of the FAME trial, further studies were conducted to build on its findings:

• FAME 2 Trial: Evaluated FFR-guided PCI in patients with stable coronary artery disease, demonstrating that FFR-guided PCI reduced urgent revascularization and myocardial infarction compared to medical therapy alone.
• Long-Term Outcomes: Subsequent analyses of the FAME trial population have confirmed the long-term benefits of FFR-guided PCI.

References

FAME Trials

The FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) Trials are landmark clinical studies that evaluated the use of fractional flow reserve (FFR) in guiding percutaneous coronary intervention (PCI) in patients with multivessel coronary artery disease. The trials aimed to determine whether FFR-guided PCI improves clinical outcomes compared to the traditional approach of angiography-guided PCI.

FAME trial (2009)

Background

Before the FAME trials, PCI decisions were typically based on visual coronary angiography assessment. However, angiography alone does not always accurately reflect the physiological significance of coronary artery stenoses. FFR, an index measuring the pressure differences across the coronary stenosis, provides a more precise assessment of the necessity for intervention.

Study design

The FAME trial was a multicenter, prospective, randomized controlled study that enrolled 1,005 patients with multivessel coronary artery disease. Participants were randomly assigned to undergo PCI with either FFR guidance or angiography guidance. The objective of the FAME trial was to compare the outcomes of FFR-guided PCI with angiography-guided PCI in patients with multivessel coronary artery disease. The primary endpoint of the trial was the rate of major adverse cardiac events (MACE) at one year. MACE was defined as a composite of death, myocardial infarction, and any repeat revascularization. Secondary endpoints included procedure time, the amount of contrast agent used, functional class at one year, health-related quality of life, and others.

Key findings

The trial demonstrated that FFR-guided PCI significantly reduced the rate of major adverse cardiac events (MACE) compared to angiography-guided PCI. The primary endpoint, a composite of death, myocardial infarction, and repeat revascularization at one year, was 28% lower in the FFR-guided group (13.2% vs. 18.3%). The FFR group received fewer stents on average. All-cause mortality, incidence of myocardial infarction, and the need for repeat revascularization were also lower in the FFR group but did not meet statistical significance.

Implications

The FAME 1 trial established that FFR-guided PCI is superior to angiography-guided PCI in patients with multivessel coronary artery disease, leading to better clinical outcomes and fewer unnecessary stent placements.

FAME 2 Trial (2014)

Background

Building on the success of the FAME trial, FAME 2 aimed to further investigate the benefits of FFR-guided PCI, particularly comparing PCI plus medical therapy to medical therapy alone in patients with stable coronary artery disease.

Objective

The primary objective of the FAME 2 trial was to determine whether FFR-guided PCI plus optimal medical therapy is superior to optimal medical therapy alone in reducing the rate of urgent revascularization and other adverse cardiac events in patients with stable coronary artery disease.

Design

The FAME 2 trial was a prospective, randomized controlled study that enrolled 1,220 patients with stable coronary artery disease and significant FFR-detected lesions (FFR ≤ 0.80). Participants were randomly assigned to either receive FFR-guided PCI plus medical therapy or medical therapy alone.

Results

The FAME 2 trial was prematurely stopped due to a significant reduction in urgent revascularizations in the PCI group. At two years, the primary endpoint of MACE (including death, myocardial infarction, and urgent revascularization) was significantly lower in the FFR-guided PCI group compared to the medical therapy alone group.

Conclusion

The FAME 2 trial reinforced the value of FFR-guided PCI in managing stable coronary artery disease, demonstrating that PCI significantly reduces the need for urgent revascularization and improves clinical outcomes compared to medical therapy alone.

Fame 3 Trial (2021)

The FAME 3 trial (Fractional Flow Reserve vs. Angiography for Multivessel Evaluation 3) is a clinical study aimed at comparing the effectiveness and safety of two treatment approaches for patients with multi-vessel coronary artery disease (CAD): Fractional Flow Reserve (FFR)-guided percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG).

Background

Coronary artery disease is a major cause of morbidity and mortality worldwide. For patients with multi-vessel disease, the best approach to revascularization—whether through PCI with stenting or CABG—has been a topic of ongoing research and debate.

Study Design

Type: Randomized controlled trial Participants: Patients with multi-vessel coronary artery disease Intervention: FFR-guided PCI using drug-eluting stents vs. CABG Primary Outcome: Composite of major adverse cardiac and cerebrovascular events (MACCE), including death, myocardial infarction, stroke, and repeat revascularization.

Methods

Patients were randomized to undergo either FFR-guided PCI or CABG. The primary outcome was assessed at one year, with follow-up planned for longer-term outcomes.

Results

Initial results indicated that FFR-guided PCI did not achieve non-inferiority compared to CABG, with a higher rate of adverse events observed in the PCI group.

Conclusion

The FAME 3 trial suggests that CABG may be the preferred revascularization strategy for patients with multi-vessel coronary artery disease, given the higher rate of adverse events associated with FFR-guided PCI.

Impact and Implications

The findings of the FAME 3 trial contribute to the body of evidence informing clinical decisions in the management of complex coronary artery disease. It underscores the importance of individualized patient assessment and the need for ongoing research to optimize treatment strategies.

Impact and Legacy

The FAME trials have profoundly influenced the clinical management of coronary artery disease. They established the importance of using FFR to guide PCI decisions, resulting in better patient outcomes and more judicious use of stenting. These findings have been integrated into clinical guidelines, promoting the use of FFR in routine practice for evaluating coronary lesions.

References

Tonino, P. A., et al. (2009). "Fractional flow reserve versus angiography for guiding percutaneous coronary intervention." The New England Journal of Medicine, 360(3), 213-224. De Bruyne, B., et al. (2012). "Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease." The New England Journal of Medicine, 367(11), 991-1001.

FAME 3 Trial

The Fractional Flow Reserve versus Angiography for Multivessel Evaluation 3 (FAME 3) trial is a clinical study designed to compare the outcomes of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary artery disease. The trial aims to determine the most effective revascularization strategy for improving clinical outcomes in these patients.

Background Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Multivessel disease, involving significant blockages in multiple coronary arteries, poses a particular challenge in terms of optimal revascularization strategy. Traditionally, CABG has been considered the gold standard for such cases. However, advancements in PCI techniques and the use of FFR to guide intervention have prompted investigations into whether PCI could offer comparable outcomes to CABG.

FAME 3 Trial Design Objective: To compare the effectiveness of FFR-guided PCI with CABG in patients with multivessel coronary artery disease. Design: Randomized controlled trial. Participants: Patients with significant multivessel coronary artery disease suitable for both PCI and CABG. Intervention: PCI Group: Patients undergo FFR-guided PCI, where FFR is used to measure the pressure differences across coronary artery stenoses to determine the necessity of stenting. CABG Group: Patients undergo standard coronary artery bypass grafting surgery. Primary Endpoint: The primary endpoint is a composite of death, myocardial infarction, stroke, or any revascularization at one year. Secondary Endpoints: Secondary endpoints include individual components of the primary endpoint, quality of life measures, and cost-effectiveness. Key Findings The results of the FAME 3 trial are anticipated to provide critical insights into the comparative effectiveness of FFR-guided PCI versus CABG for multivessel coronary artery disease. These findings could influence clinical guidelines and decision-making processes for the management of patients with complex coronary artery disease.

Implications If FFR-guided PCI is shown to be non-inferior or superior to CABG in terms of clinical outcomes, it could lead to a paradigm shift in the treatment of multivessel coronary artery disease, offering a less invasive alternative to surgery. This could be particularly beneficial for patients who are high-risk surgical candidates or prefer a less invasive approach.

Conclusion The FAME 3 trial represents a significant effort to optimize the treatment strategy for patients with multivessel coronary artery disease. By comparing FFR-guided PCI with CABG, the trial seeks to provide robust evidence to guide clinical practice and improve patient outcomes.

References Stone, G. W., et al. (2021). "Fractional Flow Reserve–Guided PCI as Compared with Coronary Bypass Surgery." The New England Journal of Medicine, 385(23), 2218-2229. "FAME 3 Trial." ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02100722 Fearon, W. F., et al. (2021). "FFR-Guided PCI versus CABG in Multivessel Coronary Artery Disease." Circulation, 144(13), 1115-1123.