A meta-analysis of individual patient-level data from FAME 2, DANAMI-PRIMULTI and Compare-Acute indicates that percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) is associated with a significant reduction in a composite of cardiac death and myocardial infarction compared with optimal medical therapy. These findings add to those of the five-year results of FAME 2, which showed FFR-guided PCI to reduce the risk of spontaneous myocardial infarction.
Writing in the European Heart Journal, Frederik M Zimmerman (Department of Cardiology, Catharina Hospital, Eindhoven, The Netherlands) and others conducted a “collaborative individual patient data meta-analysis” of trials that compared FFR-guided with optimal medical therapy “to resolve a key uncertainty in clinical practice for a frequently performed, invasive and expensive procedure” (PCI in patients with stable/stabilised disease). The pre-specified primary outcome was a composite of cardiac death or myocardial infarction, with secondary outcomes including the composite of all-cause death or myocardial infarction and the individual components of these composite outcomes.
Zimmerman et al reviewed data from FAME 2, DANAMI-PRIMULTI and Compare-Acute—the first of these reviewed FFR-guided PCI in patients stable disease and the other two reviewed FFR-guided PCI in non-culprit lesions of patients with ST-segment elevation myocardial infarction (STEMI) who had successfully undergone treatment of the culprit lesion. All of the studies assessed PCI with second-generation drug-eluting stents. Of 2,400 patients overall, 1,056 had been randomised to FFR-guided PCI and 1,344 to optimal medical therapy.
After a median follow-up of 35 months, FFR-guided PCI was associated with a 28% relative risk reduction in the primary endpoint compared with optimal medical therapy (p=0.02). “The estimated cumulative incidence [of the primary endpoint] at five years was 10.7% for FFR-guided PCI group and 16.4% for the primary endpoint, which resulted in an estimated number needed to treat to prevent one event up to five years of 18,” Zimmerman et al report. They add that the difference between groups was driven by a difference in myocardial infarction (use of FFR-guided PCI had a number needed to treat of 20 to prevent one myocardial infarction at five years). However, there were no significant differences between FFR-guided PCI or optimal medical therapy in the rate of cardiac death or all-cause death. The authors observe: “For the secondary composite of all-cause death or myocardial infarction, there was a 23% relative reduction in FFR-guided PCI (p=0.04)”.
According to Zimmerman et al, “two factors” explain why none of the individual trials that compare PCI have shown it to reduce a composite of cardiac death or myocardial infarction in patients with stable/stabilised disease. The first of these is that the trials were underpowered for the composite of cardiac death or myocardial infarction; the authors note: “Because all trials were powered for a primary composite endpoint that included various definitions of revascularisation as one of its components, it cannot be expected that a statistically significant reduction in cardiac death or myocardial infarction would be found in any single trial”. The second factor is that earlier trials that assessed the use of PCI in the context of stable/stabilised disease used bare metal or first-generation drug-eluting stents and used angiography rather than FFR.
The authors conclude: “In this individual patient-level data meta-analysis of the three available randomised controlled trials to date, FFR-guided PCI resulted in a reduction of the composite of cardiac death or myocardial infarction compared with medical therapy, which was driven by a decreased risk of myocardial infarction.”
Zimmerman and study author Nico HJ Pijls (Department of Cardiology, Catharina Hospital, Eindhoven, The Netherlands) told Cardiovascular News: “A classical dispute resolved: PCI reduces hard endpoints, not only in acute coronary syndrome but also on the long-term instable angina.”