FAME 2: FFR-Guided PCI Continues on Same Trajectory from 1 to 2 Years

BARCELONA, Spain—Data from the FAME 2 trial, presented September 2, 2014, at the European Society of Cardiology Congress and simultaneously published online in the New England Journal of Medicine, show that percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) continues to benefit patients with stable coronary artery disease (CAD) more than medical therapy alone through 2 years.

Methods
For the FAME 2 (Fractional flow reserve versus Angiography for Multivessel Evaluation 2) trial, Bernard De Bruyne, MD, PhD, of Cardiovascular Center Aalst (Aalst, Belgium), and colleagues measured FFR in 1,220 patients with stable CAD who had angiographic evidence of stenosis in at least 1 coronary vessel. 
The 888 patients who were determined to have at least 1 flow-limiting lesion (FFR ≤ 0.8) were randomized to optimal medical therapy with (n = 447) or without (n = 441) FFR-guided PCI. The remaining 332 patients were enrolled in a registry and treated with optimal medical therapy.
Enrollment in FAME 2 was halted early at only 54% of its planned sample size after an interim analysis determined that, compared with those on optimal medical therapy alone, FFR-guided patients had 68% lower risk of the primary composite endpoint of all-cause death, MI, or urgent revascularization.


Just as at 1 year, the primary endpoint at 2 years was lower in patients randomized to PCI compared with medical therapy, a difference driven by urgent revascularization. No between-group differences were seen for death or MI (table 1). 

Table 1. Two-Year Clinical Outcomes

PCI 

(n = 447)

Medical Therapy 

(n = 441)

HR (95% CI)

P Value

Primary Endpoint

8.1%

19.5%

0.39

(0.26-0.57)

< .001

Death

1.3%

1.8%

0.74

(0.25-2.14)

.58

Urgent Revascularization

4.0%

16.3%

0.23

(0.14-0.38)

< .001

MI

5.8%

6.8%

0.85

(0.50-1.45)

.56

 

Additional calculations further tipped the balance in favor of PCI. Urgent revascularization triggered by MI or ischemic changes on ECG was less common with PCI (3.4% vs 7.0%; P = .04). Landmark analysis excluding events within 7 days showed lower risk of death/MI in the PCI group compared with the medical therapy group (4.6% vs 8.0%; HR 0.56; 95% CI 0.32-0.97) but did not change the strength of the reduction in urgent revascularization with PCI.

Moreover, Dr. De Bruyne said, the death/MI curves continued to separate over time up to 2 years.

Dr. De Bruyne drew attention to the registry patients, whose 2-year rate of the primary endpoint was 9.0%. “It’s also important to emphasize that patients in whom all the lesions appeared to be hemodynamically nonsignficant did very well with medical therapy alone,” he said. 

“I think we can conclude that in patients with stable coronary artery disease, PCI improves outcome—and more specifically that FFR-guided PCI with the placement of drug-eluting stents of the second generation improves outcome compared with medical therapy alone,” Dr. De Bruyne commented. 

‘Recall Bias’ a Concern  

Discussant Udo Sechtem, MD, of Robert-Bosch Medical Center (Stuttgart, Germany), said ‘recall bias’ could explain the uptick in revascularization for medical therapy patients.

“If you tell the patient that he has a significant stenosis that was left untreated, and that patient gets chest pain, he will be absolutely in panic,” Dr. Sechtem observed. “He will go to the hospital and want to have treatment. And indeed, we see that the most common trigger was resting angina… not always with objective signs of damage.” 

When considering the 2-year reduction in the primary outcome, “the differences are not very impressive” if focused on more “objective triggers” such as ACS with troponin rise or ECG changes, he stressed. Also, he added, so few events occurred between 1 and 2 years that the data could be vulnerable to play of chance and potential bias. 

What Happens Before the Cath Lab?  

“If one intends to revascularize a patient who would fit the FAME 2 trial… of course you need FFR guidance,” Dr. Sechtem concluded, emphasizing that 25% of patients with angiographic evidence of stenosis did not turn out to have functionally significant lesions and did just as well with medical therapy as did the patients randomized to PCI.

Crucially, he added, clinicians should follow guideline recommendations when treating patients with stable CAD.

Session chair Robert A. Harrington, MD, of Stanford University School of Medicine (Stanford, CA), reiterated the latter point. “A big part of the guidelines is what we do before we get to the cath lab,” he said. “I’m struck by the fact that a quarter of the patients don’t end up having hemodynamically significant disease…. Could we have prevented cath in a good number of these patients to begin with?”

Dr. De Bruyne said that 23% of patients underwent noninvasive testing prior to angiography. “You might be surprised,” he said, but noted that this number reflects what is known from registries. “We know very well that less than half of patients with stable angina have ever had noninvasive testing before any procedure, not even a coronary angiogram.”

In FAME 2, he continued, “we were dealing with centers very experienced with [FFR] and where the strategy of sending the patient to the cath lab has changed tremendously over the years, namely that the threshold to go to the cath lab is much lower because [there] we can obtain both the anatomy and the physiology together. All the noninvasive pathways are very often bypassed at these centers.”


Sources: 
1. De Bruyne B, Fearon WF, Pijls NHJ, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med. 2014;Epub ahead of print.
2. Rade JJ. FFR-guided PCI: FAME may not be so fleeting after all [editorial]. N Engl J Med. 2014;Epub ahead of print.

Related Stories:

Disclosures
  • FAME 2 was supported by St. Jude Medical.
  • Dr. De Bruyne reports that his institution receives research grant support and consulting fees on his behalf from St. Jude Medical.

We Recommend

Comments