Clinical outcomes and cost-effectiveness of fractional flow reserve-guided percutaneous coronary intervention in patients with stable coronary artery disease
Selected in Circulation by D. Milasinovic
Three-year follow-up of the FAME 2 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation).
Fearon WF, Nishi T, De Bruyne B, Boothroyd DB, Barbato E, Tonino P, Jüni P, Pijls NHJ, Hlatky MA; FAME 2 Trial Investigators.
Circulation. 2017 Nov 2. pii: CIRCULATIONAHA.117.031907
LinkRead the abstract
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Why this study – the rationale/objective?
FAME 2 trial showed the benefit of PCI vs. medical therapy in patients with FFR≤0.80, primarily in terms of the reduced rate of urgent revascularization. This extended follow-up study investigated the impact of FFR-guided PCI on 3-year clinical outcomes, quality of life and cost effectiveness in treating patients with stable angina.
How was it executed – the methodology?
- 1220 patients with at least one angiographically appearing stenosis ≥50% were enrolled, of which 888 had at least one stenosis with FFR≤0.80, and were randomized to PCI (n=447) or medical therapy (n=441).
- The primary endpoint (MACE) included all-cause death, non-fatal MI and urgent revascularization (the follow-up rate was 94% in both groups at 3 years).
- Cost analysis was performed from the perspective of US healthcare system and quality of life was assessed based on European Quality of Life-5 Dimensions (EQ-5D) with US weighting.
What is the main result?
- MACE was reduced in PCI-treated patients (10.1% vs. 22.0%, p<0.001), mainly due to a large reduction in the rate of urgent revascularization (4.3% vs. 17.2%, p<0.001), albeit a non-significant reduction in death or MI was also noted (8.3% vs. 10.4%, p=0.28).
- The rate of CCS II-IV angina was significantly lower in PCI-treated patients, although the gap seems to have been closing with time (44.2% of patients in the medical therapy group underwent a late PCI).
- Initially higher treatment costs in the PCI group were offset by the accrual of expenses related to later revascularization procedures in the medical therapy group.
Critical reading and the relevance for clinical practice
The 3-year results of the FAME 2 trial reassert its initial findings that in patients with baseline FFR≤0.80, not performing PCI is associated with a continuously increased risk of urgent (and non-urgent) revascularization procedures, and a higher symptom burden, ultimately evening out the initially higher costs of PCI at baseline. These findings coincide timely with the publication of the ORBITA trial, that seems to convey a different message – PCI has no benefit over medical therapy in patients with stable CAD. The main advantage of the ORBITA trial seems to be the fact that it was a true placebo-controlled interventional trial, where a sham procedure was performed, and patients and outcome assessors were unaware of the treatment (PCI or medical therapy).
However, in addition to the debate regarding the choice of the primary endpoint and the effect size, and the length of the follow-up (only 6 weeks in the ORBITA trial), one of the arguments voiced, to explain the failure of PCI to show benefit over a sham intervention in the ORBITA trial, was the low-risk, low baseline angina burden patient population (only single vessel, and ≈30% of patients had baseline FFR>0.80, despite an angiographically appearing significant stenosis). It seems that this argument could be a sort of a link between the findings of FAME 2 and ORBITA, suggesting that a certain threshold of ischemia may need to be reached for PCI to have a clinical effect, and thus patient selection for PCI to be the key. Future physiology-based studies and the approaching era of precision medicine may perhaps better characterize the role of PCI in stable coronary artery disease, by offering more insight into the patient selection process.
What is the opinion of the community on the latest trials on the effects of PCI in stable CAD? Do you consider the results practice-changing?