Reed Miller

October 25, 2012

MIAMI — A cost-effectiveness analysis of the St Jude-sponsored FAME II trial shows that fractional-flow-reserve (FFR)–guided PCI is a cost-effective alternative to optimal medical management in stable patients with flow-limiting coronary lesions [1,2].

The cost-effectiveness analysis was presented here at TCT 2012 by Dr William Fearon (Stanford University, CA). "Based on COURAGE, people have argued that up-front optimal medical therapy should be achieved before proceeding to PCI, but what we showed in FAME II was that if you can identify ischemia-producing lesions and isolate those, patients [with those lesions] benefit from PCI up front as compared with optimal medical therapy, by decreasing urgent revascularization and improving quality of life," he said.

Fearon explained that optimal medical therapy for these patients costs about $2508 less in the first year than percutaneous intervention to treat the coronary lesions shown to be flow-limiting by FFR. But, by reducing angina and the need for urgent revascularization, FFR-guided PCI leads to a better quality of life, and the overall cost-effectiveness of the FFR-guided PCI approach over medical therapy was $53 000 per quality-adjusted life-year, which is comparable to other widely accepted therapies, Fearon said.

By contrast, the cost-effectiveness analysis from COURAGE trial found that, compared with optimal medical therapy, PCI guided only by angiography has a cost-effectiveness ratio of $168 000 per quality-adjusted life-year.

"We want to be conservative and not overstate things," Fearon said. "We don't have longer follow-up at this time, but . . . the benefit of PCI lasted more than one year in COURAGE, and freedom from angina [in the PCI group] lasted out to three years." The investigators project that at three years, the cost-effectiveness ratio of the FFR-guided PCI approach over medical therapy alone will be $32 000 per quality-adjusted life-year.

As reported by heartwire , FAME II included 1220 patients examined by FFR following symptoms of stable coronary disease. The 888 patents with at least one flow-limiting lesion, defined as an FFR <0.80, were randomized to either PCI or optimal medical therapy. Patients without any flow-limiting lesions were put into a registry.

The trial was stopped last year after the interim analysis showed that patients randomized to PCI were much less likely to need an urgent revascularization than patients randomized to optimal medical therapy. Although the "hard end points" of death and MI were about the same for both strategies, two years after randomization, 11.1% of the optimal-medical-management patients had undergone an urgent revascularization compared with only 1.6% of the PCI patients, so the composite end point was 12.7% and 4.3% in the medical-management and PCI groups, respectively (p<0.001).

In addition to the difference in urgent revascularization, the PCI patients were significantly less likely to have angina one month after the procedure than comparable medical-management patients (29% vs 52%, p<0.001), Fearon stressed. In the quality-of-life analysis, the difference in angina resulted in a significantly greater "change in utility" from baseline to one month in the FFR-guided PCI patients than the medical-therapy patients (0.054 vs 0.003), he said.

Will Difference Angina and Revascularization Alone Make a Difference?

At TCT, Dr David Faxon (Brigham and Women's Hospital, Boston, MA) pointed out that currently, most cardiologists' approach to these stable-angina patients is to wait to see if their angina improves on medical therapy and then intervene if it does not. He questioned whether clinicians would be willing to change their practice without any demonstrated improvement in death or MI.

Fearon conceded that "in the short time horizon of the study, there was no hard end point, and we don't know if we'd follow the patients further that would have changed, although our landmark analysis shows that it might."

However, he argued, "It's not fair to shortchange the improvement in quality of life that a reduction in having to come back urgently to the hospital for a revascularization [confers], and I think this component is key because now it adds the cost relationship to this and shows it's a cost-effectiveness strategy."

Dr Bernard Gersh (Mayo Clinic, Rochester, MN), who was on the data safety monitoring board that terminated the trial, suggested that some of the "urgent revascularizations" may not really have been urgent. Since the patients knew they had a flow-limiting lesion, they might have been more apt to seek medical attention for angina symptoms than patients outside of such a trial would be.

But Fearon pointed out that, among the patients in FAME II put in the registry because FFR showed them to have only hemodynamically insignificant lesions, the rate of urgent revascularizations was about half of that seen in the patients randomized to FFR-guided PCI. "These patients knew they had a lesion too, and yet they didn't present with urgent revascularizations at the rate of the patients with hemodynamically significant ones."

He also cited a subset analysis showing that even if urgent revascularization is redefined to mean only those revascularizations driven by measured biomarker elevations or ECG changes, the FFR-guided patients still had a much lower rate of revascularization than the medically managed patients (83% relative risk reduction, p<0.0001).

Fearon said that the adoption of FFR has been increasing since FAME I showed that the routine measurement of FFR-guided PCI can reduce mortality and MI compared with angiography-guided PCI in patients with multivessel disease, and he expects the results of FAME II and now this cost-effectiveness analysis to drive more interest in FFR.

"The practical barriers include familiarity with the technique, learning how to do it, and I think those barriers will come lower and lower and we'll see a continued uptick in its use," he said.

FAME II was sponsored by St Jude Medical.