FAME 2 at 3 Years: Outcomes, Symptoms Better With PCI vs OMT in Stable CAD, at Similar Cost

DENVER, CO—PCI in patients with stable CAD and functionally significant stenosis leads to improved clinical outcomes and quality of life (QoL) over the long term, as compared with optimal medical therapy (OMT) alone, according to 3-year data from the FAME 2 trial. Importantly, the invasive approach also becomes more “economically attractive” as the years go by.

Previously, the FAME 2 researchers had shown that PCI was initially more expensive than OMT alone, but that the money saved by avoiding repeat revascularization in the year after treatment substantially narrowed that gap. The 3-year follow up data, presented here today in a late-breaking clinical trial session at TCT 2017, add even more evidence to support the economics of PCI as the initial strategy by showing no difference in cost at 3 years, strikingly fewer urgent revascularizations, and a high rate of crossover to PCI.

Study presenter William F. Fearon, MD (Stanford University Medical Center, CA), said the results “reinforce the fact that the greater burden of ischemia, the greater the benefit of revascularization with PCI.”

FAME 2 enrolled 1,220 patients from 28 sites in Europe and North America. All had stable CAD and angiographically significant stenosis. FFR was measured in all target lesions. Those with at least one flow-limiting lesion (FFR ≤ 0.80), which constituted 73% of the population, were randomized to OMT with or without FFR-guided PCI, while the other 27% with FFR > 0.80 were enrolled in a registry and received OMT only.

The study was halted early when interim data showed substantially fewer events related to the primary composite endpoint of all-cause death, MI, or urgent revascularization in the FFR-guided group.

Urgent Revascularizations Quadrupled With OMT

The 3-year data presented here showed that patients who received OMT had a higher rate of the composite endpoint compared with the PCI or registry patients. MACE occurred in 10.1% of the PCI-treated patients versus 22% of the OMT patients (P < 0.001). Additionally, death and MI were numerically lower in the PCI arm, but the difference did not reach statistical significance. The incidence of urgent revascularizations was more than four times higher in the OMT group than in the PCI patients (17.2% vs 4.3%; P < 0.001).

Among patients with Canadian Cardiovascular Society (CCS) class II-IV angina, symptoms were lower at all time points throughout the 3-year follow up in the PCI group. Importantly, 44% of patients in the OMT-only arm crossed over to PCI at some point, Fearon noted. The mean number of antianginal drugs was significantly lower among the PCI versus the OMT-only patients, as were measures of resource utilization from baseline through 3 years.

While baseline costs for the PCI group were more than twice as high at 1 year compared with OMT, “over time, costs were higher at each time point in the medical therapy group such that at 3 years there was no difference in cumulative costs between the two groups,” Fearon said.

At 2 years, quality-adjusted life-years (QALY) were higher in the PCI arm and costs were slightly higher resulting in an incremental cost-effectiveness ratio (ICER) for PCI of $17,300 per QALY. At 3 years, the ICER for PCI was even more economically attractive at $1,600 per QALY.

According to Fearon, the findings were “robust” on a number of sensitivity analyses, including one in which the costs of initial angiogram and FFR measurement were eliminated in the OMT arm. Using a “last value carried forward” computation, the QALY at 3 years was numerically higher in the PCI group than with OMT, and costs were numerically lower.

Ischemic Burden Is Key

Following the presentation, moderator Gregg W. Stone, MD (NewYork-Presbyterian/Columbia University Medical Center, New York, NY), asked Fearon if the results could be due to lack of placebo control—a question spurred by the sham-controlled ORBITA trial, which preceded Fearon’s presentation. In ORBITA, also conducted in stable CAD patients, but with single-vessel disease only and no mandated FFR cut point, PCI proved no better than a sham procedure in improving exercise capacity or symptom relief.

Responding to Stone’s question, Fearon said he felt it was unlikely, adding “it’s hard to imagine a placebo effect lasting 3 years.”

Panelist Stephen G. Ellis, MD (Cleveland Clinic Foundation, Cleveland, OH), said his take on the study is that it supports the notion that an initial strategy of medical therapy is not unreasonable, “but we certainly seem to be justified in performing PCI” in this patient cohort.

Regarding the lack of statistical difference in death and MI between the groups, Fearon pointed to the rate of crossovers in the study: 44.2% of patients in the medical therapy group subsequently underwent PCI over the follow-up period. Had they not done so, he said, “we could potentially have seen higher rates of death and MI.”

Panelist Allen Jeremias, MD, MSc (St. Francis Hospital, Roslyn, NY), said the entire FAME trial series has furthered the understanding of this complex patient population.

Like Fearon, he said ischemic burden is clearly the main factor to consider in stable CAD patients, adding that while those with higher burden constitute higher risk and would therefore be candidates for PCI, in those with lower burden, “it might be safe to treat medically, if that’s their choice.”

Stone added that the FAME investigators “have shown again and again that the lower the FFR, the higher the event rate. So, there’s ischemia, and then there’s ischemia. There are symptoms and then there are symptoms. . . . We have to look at each individual patient according to the constellation of their symptoms and physiology.”