Three late-breaking clinical trials that explored the use of fractional flow reserve (FFR) and the instantaneous wave-free ratio (iFR) index for clearing blockages and as diagnostic tools have shown these approaches are beneficial, according to research presented at ACC.17 in Washington, DC, and simultaneously published in the New England Journal of Medicine.

The DEFINE-FLAIR and iFR-SWEDEHEART trials demonstrated that iFR was equivalent to FFR in terms of incidence of major adverse events in patients experiencing angina or a myocardial infarction (MI). The studies also showed iFR resulted in markedly less patient discomfort and reduced procedure-related adverse events compared with FFR. Although iFR has been validated in several smaller studies, these two new trials are the largest to date and the first to assess how using the method affects patient outcomes.

Both FFR and iFR are based on coronary physiology, a direct, internal measure of coronary flow and pressure within the arteries. FFR has been underutilized in practice, in part because it takes more time and may cause some discomfort, chest pain and shortness of breath for some patients, researchers said.

The study results suggest that iFR could offer the same benefits as FFR while avoiding its downsides. The studies showed no significant difference between iFR and FFR for the primary endpoint, which was in both trials a composite of all-cause mortality, non-fatal MI and unplanned revascularization at 12 months.

"Our study shows that it is safe to use either the iFR or FFR technique," said Justin E. Davies, MBBS, PhD, lead author of DEFINE-FLAIR. "I think iFR lowers the barriers to physiological measurement, which I believe is key to getting more people to use coronary physiology to guide coronary revascularization decision-making."

Like FFR, iFR is based on coronary blood pressure measurements using a thin pressure sensor wire, but unlike FFR, it uses a mathematical algorithm to measure the pressure in a coronary artery only when the heart is relaxed and the coronary blood flow is high. As a result, a vasodilator drug is not needed.

"If patients could choose between two methods, given that there is no difference in outcomes, patients would probably appreciate not having to experience the side effects of the vasodilator," said Matthias Götberg, MD, PhD, lead author of iFR-SWEDEHEART. "For cardiologists who are hesitant to use FFR, iFR might provide an opportunity to increase adoption rates of coronary physiology and benefit more patients."

Both DEFINE-FLAIR and iFR-SWEDEHEART enrolled patients who had stable angina or acute coronary syndrome and needed coronary physiology to inform treatment. For patients enrolled after an MI, the studies only included data related to blockages other than the one for the index MI.

In DEFINE-FLAIR, researchers enrolled 2,492 patients at 49 centers in 17 countries. Half of the patients received iFR and half received FFR. In iFR-SWEDEHEART, researchers enrolled 2,037 patients at 15 centers in Sweden, Denmark and Iceland. A total of 2,019 patients in this study were treated according to protocol, with 1,012 patients receiving iFR and 1,007 receiving FFR.

iFR-SWEDEHEART revealed a substantial reduction in patient discomfort, with just 3 percent of iFR patients reporting discomfort in a post-procedure questionnaire compared with 68 percent of FFR patients. DEFINE-FLAIR showed a substantial reduction in symptoms of both patient-reported and physician-reported procedure-related adverse events, which occurred in 3 percent of iFR patients and 30.8 percent of FFR patients overall. No significant differences in separate analyses of all-cause mortality, subsequent MI or revascularization were found in either study.

Compare-Acute is the first randomized clinical trial in which physicians used FFR to precisely assess secondary blockages. Compared with patients in whom only the infarct-related blockage was treated, patients who received FFR-guided evaluation and treatment of all significantly narrowed arteries were 65 percent less likely to experience the trial's primary endpoint, a composite of all-cause mortality, non-fatal MI, stroke and subsequent revascularization at 12 months.

In Compare-Acute, 885 STEMI patients were enrolled at 24 sites in 12 countries in Europe and Asia. Immediately after PCI for the infarct-related artery, stable patients were randomly assigned to receive FFR-guided assessment of other arteries but no additional PCI (infarct-only revascularization; 590 patients) or FFR-guided assessment and PCI to treat additional lesions when indicated by an FFR of 0.80 or lower (complete revascularization; 295 patients).

The primary endpoint – a composite of all-cause mortality, non-fatal MI, stroke and subsequent revascularization at 12 months – occurred in 20.5 percent of patients receiving infarct-only revascularization and 7.8 percent of patients receiving FFR-guided complete revascularization, a difference that was statistically significant. When the components of the composite primary endpoint were analyzed separately, there was no significant difference in the rates of all-cause mortality, non-fatal MI or stroke; however there was a significant reduction in the incidence of subsequent revascularization procedures among patients randomized to receive complete revascularization.

All non-urgent revascularization procedures performed within the first 45 days after the initial PCI based on symptoms or stress tests were excluded from this analysis to avoid biasing the results in favor of complete revascularization.

When assessing the lesions other than infarct-related artery, the researchers found that about half of these lesions were sufficiently constricted to require treatment. Together, these results suggest that treating non-infarct related lesions is beneficial and that FFR can help clinicians to precisely identify these lesions.

"The results show that using FFR in the acute phase of STEMI is feasible and safe," said lead author Pieter Smits, MD. "Furthermore, FFR-guided complete revascularization allows you to fine-tune the treatment and get better outcome results."

Keywords: ACC17, ACC Annual Scientific Session, Acute Coronary Syndrome, Adenosine, Angiography, Arteries, Hemodynamics, Myocardial Infarction, Vascular Diseases, Cause of Death, Constriction, Pathologic, Coronary Stenosis, Cost-Benefit Analysis, Fractional Flow Reserve, Myocardial, Random Allocation, Angina, Stable, Angioplasty, Coronary Angiography, Myocardial Revascularization, Outcome Assessment, Health Care, Registries, ACC Scientific Session Newspaper

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