The use of fractional flow reserve to guide percutaneous coronary intervention, along with best medical management, sharply reduced the need for urgent revascularization in patients with stable coronary artery disease and at least one physiologically significant lesion.
However, FFR-guided percutaneous coronary intervention (PCI) had little effect on deaths or myocardial infarctions, when compared with best medical management alone, according to the results of the FAME 2 (Fractional Flow Reserve vs. Angiography for Multivessel Evaluation 2) trial, which was conducted at 28 sites in Europe and North America and halted early.
The percentage of patients who had an MI, death, or urgent revascularization (the combined primary end point) was significantly lower in the PCI group than in the medical therapy group (4.3% vs.12.7%; hazard ratio with PCI, 0.32). This difference was driven by a 13-fold increase in the need for urgent revascularization in the medical-therapy group. Notably, the rate of death from any cause and the rate of MI did not differ significantly between the PCI group and the medical therapy group.
Importantly, patient recruitment was stopped on Jan. 15, 2012, at the recommendation of an independent data and safety monitoring board because of the highly significant difference in the incidence rates of the primary end point between the PCI and medical-therapy groups.
The results of the study were released in the New England Journal of Medicine on Aug. 28 to coincide with the presentation of the study at the annual congress of the European Society of Cardiology (N. Engl. J. Med. 2012 Aug. 28 [doi:10.1056/NEJMoa1205361]).
A total of 1,220 patients out a planned 1,832 were enrolled. Of those, 888 patients had at least one stenosis with an FFR of 0.80 or less: 447 patients were randomly assigned to FFR-guided PCI plus the best available medical therapy, and 441 patients to the best available medical therapy alone. The 332 patients with angiographically significant stenoses, but none with an FFR of 0.80 or less were enrolled in the registry and received the best available medical therapy alone. The mean duration of follow-up was 212 days.
Patients in stable condition who were appropriate candidates for PCI and who had angiographically assessed one-, two-, or three-vessel coronary artery disease suitable for PCI were included in the trial.
All patients were prescribed aspirin at a dose of 80-325 mg daily, metoprolol at a dose of 50 mg-200 mg daily (or any other beta-blocker), lisinopril (at least 5 mg daily, or another ACE inhibitor or an angiotensin receptor blocker)and atorvastatin (20-80 mg daily, or another statin).
All PCI patients were treated with second-generation drug-eluting stents.
Among the 56 patients who underwent urgent revascularization, the procedure was triggered by a MI in 12 patients (21%), by unstable angina accompanied by evidence of ischemia on ECG in 15 patients (27%), and by unstable angina diagnosed on the basis of clinical features in 29 patients (52%).
Patients in the PCI group were 86% less likely to undergo any revascularization and 83% less likely to undergo or nonurgent revascularization than were those in the medical therapy group.
The researchers identified several factors that may explain the differences between results in the present study and those in previous trials involving patients with stable coronary disease. "First, in previous trials in which various revascularization methods were compared with the best available medical therapy, patient enrollment was based primarily on angiographic findings, with or without noninvasive documentation of ischemia. It is likely that a sizable proportion of the patients had only limited ischemia," wrote lead investigator Dr. Bernard B. De Bruyne and his coinvestigators. Dr. De Bruyne is the codirector of the Cardiovascular Center at OLV Hospital in Aalst, Belgium.
"Even in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, in which noninvasive testing was performed in 85% of the patients, less than one-third of the patients had more than 10% ischemia on myocardial perfusion imaging. In daily clinical practice, less than half of patients undergo noninvasive stress testing before elective PCI. In the current trial, all the patients who underwent randomization had at least one functionally significant stenosis," they observed (N. Engl. J. Med. 2007;356:1503-16).
Second, PCI was performed only in lesions with an FFR of 0.80 or less. "This FFR-guided approach is associated with a better clinical outcome than that with PCI performed on the basis of angiographic results alone. These features probably explain the similarity of event rates between patients who were treated with PCI plus the best available medical therapy and patients with equivalent baseline characteristics but no functionally significant lesions who were enrolled in the registry and treated with the best available medical therapy alone," according to the investigators.