FFR-Guidance Demonstrates Benefits in Patients with Unstable Angina, NSTEMI

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Patients with multivessel disease and unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) derive as much benefit from fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) as do those with stable angina, according to a subanalysis of the FAME trial reported in the November 2011 issue of JACC: Cardiovascular Interventions.

In FAME (Fractional Flow Reserve vs. Angiography for Guiding PCI in Patients with Multivessel Evaluation), 1,005 patients with multivessel CAD were randomized to PCI guided by angiography with (n = 509) or without (n = 496) FFR. The study was conducted at 14 participating centers in Europe and 6 in the United States. The main results showed that at 1 year, those randomized to FFR-guided PCI had lower rates of death, MI, or repeat revascularization than those receiving angiographic guidance alone (13.2% vs. 18.3%; P = 0.02).

For the new subanalysis, lead FAME investigator, Nico H. J. Pijls, MD, PhD, of Catharina Hospital (Eindhoven, The Netherlands), and colleagues compared the 328 patients in the study who had an initial diagnosis of unstable angina or NSTEMI with the 677 who had stable angina. Unstable angina or NSTEMI patients had positive troponin but total creatine kinase less than 1,000 U/l.

Similar Risk Reduction, MACE

For procedural results, there was no difference between patients with unstable angina/NSTEMI and patients with stable angina with respect to the number of indicated lesions per patient, the percentage of hemodynamically significant lesions within the FFR-guided groups, or the percentage of successfully treated lesions. There also were no significant differences in procedure time, contrast use, number or type of stents used, or use of glycoprotein IIb/IIIa inhibitors. However, hospital stay was significantly longer for patients with unstable angina/NSTEMI than for patients with stable angina (4.5 ± 4.5 days vs. 3.1 ± 2.7 days; P < 0.01).

In the unstable angina/NSTEMI group, FFR guidance resulted in an average 1 stent less per patient compared with angiography guidance alone (1.9 ± 1.5 vs. 2.9 ± 1.1; P < 0.01), as well as less contrast (269 ± 139 mL vs. 308 ± 134 mL; P = 0.01).

At 2 years, there was no evidence for heterogeneity in effect of FFR guidance among any subgroups. In patients with unstable angina/NSTEMI, the absolute reduction for MACE (death, MI, CABG, or repeat PCI) at 2 years with FFR guidance was 5.1% compared with 3.7% in patients with stable angina (P = 0.92). The relative risk reductions for MACE were 19% and 18%, respectively.

Overall, patients with unstable angina/NSTEMI had a higher rate of composite death, MI, and repeat revascularization at 2 years compared with stable angina patients. There was also a significant difference in occurrence of MI and death or MI (table 1).

Table 1. Endpoints at 2 Years


Unstable Angina
(n = 328)

Stable Angina
(n = 677)

P Value

Death/MI/CABG/Repeat Revascularization








Death or MI





Functional status at 2 years did not differ between the groups, with 74.1% of unstable angina/NSTEMI patients free of angina compared with 79.6% of stable angina patients (P = 0.07).

The study authors say the higher event rate in the unstable angina/NSTEMI group points to the negative impact of unstable coronary disease on prognosis while “at the same time showing that these patients in the FAME population are in fact at increased risk of MACE, compared with stable patients. This is reflected in similar relative risk reduction but larger absolute risk reduction by using FFR in these patients.”

Alleviates Some Concerns, But Questions Remain

Duane Pinto, MD, MPH, of Beth Israel Deaconess Medical Center (Boston, MA), told TCTMD in a telephone interview that the study sheds needed light on how to manage unstable angina and NSTEMI patients.

“It’s very interesting because we think that high-risk [NSTEMI] patients should have their arteries repaired to avoid repeat reinfarction,” Dr. Pinto said. “But there are instances where you cath someone and they have an intermediate lesion in the circumflex and an intermediate in the right coronary and you do the FFR and it’s negative for the circumflex so you go ahead and just fix the right coronary artery and leave the circumflex [alone]. The question is always whether it’s okay to do that because they may cause trouble later on, so this study validates that indeed you can leave those lesions alone.”

Dr. Pinto also said the study may help alleviate concern that FFR can be less accurate in predicting flow-limiting lesions in the midst of an acute coronary syndrome.

In a telephone interview with TCTMD, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), said the results are hypothesis generating and consistent with the idea that FFR prevents unnecessary stenting, which can expose the patient to the risk of stent thrombosis without really curing anything.

“This supports the fact that you can do multivessel PCI in the setting of NSTEMI if it is indicated,” he said.

But, Dr. Brener said the study leaves open unanswered questions such as how many lesions thought by the investigators to be culprit lesions had normal FFR and were left alone.

Study Details

In the original trial, PCI was performed with standard techniques and drug-eluting stents. FFR was measured with a coronary pressure guidewire (St. Jude Medical Systems, Uppsala, Sweden) at maximum hyperemia induced by intravenous adenosine, which was administered at a rate of 140 µg/kg/min. Pressure pullback recordings were performed in all indicated arteries. Use of periprocedural glycoprotein IIb/IIIa antagonists was at the discretion of the operator. After PCI, all patients were treated with aspirin and clopidogrel for at least 1 year.


Sels J-WEM, Tonino PAL, Siebert U, et al. Fractional flow reserve in unstable angina and non–ST-segment elevation myocardial infarction: Experience from the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) study. J Am Coll Cardiol Intv. 2011;4:1183-1189.



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  • FAME was supported by unrestricted research grants from Radi Medical Systems and Stichting Vrienden van het Hart Zuidoost Brabant.
  • Dr. Pijls reports having received an educational grant from St. Jude Medical.
  • Drs. Brener and Pinto report no relevant conflicts of interest.