By Jeffrey Zimmet, MD, PhD

Associate Professor of Medicine, University of California, San Francisco, Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center

Dr. Zimmet reports no financial relationships relevant to this field of study.

SYNOPSIS: Researchers recently found that deferral of percutaneous coronary intervention based on fractional flow reserve and instantaneous wave-free ratio is equally safe, with a low one-year major adverse cardiac event rate of approximately 4%.

SOURCE: Escaned J, Ryan N, Mejía-Rentería H, et al. Safety of the deferral of coronary revascularization on the basis of instantaneous wave-free ratio and fractional flow reserve measurements in stable coronary artery disease and acute coronary syndromes. JACC Cardiovasc Interv 2018;11:1437-1449.

In the cardiac catheterization laboratory, clinicians recognize that visual estimates of lesion severity are limited, especially in cases of intermediate coronary stenoses. Physiologic measures have proven superior, with fractional flow reserve (FFR) taking the place as the default standard. Clinicians should recognize that the superiority of FFR-guided intervention (compared to guidance by angiography alone) demonstrated in investigations such as the FAME trial was based on the ability of the physiologic test to determine which lesions on which not to intervene. In general, the use of FFR results in fewer interventions compared to decision-making by angiography. The strategy of using a high FFR value to support conservative management of a lesion was based primarily on the outcomes of the 2001 DEFER trial, whose authors randomized 325 patients with FFR values > 0.75 to medical therapy or to percutaneous coronary intervention (PCI). DEFER was relatively small, included only patients with stable angina, and was performed in a different era of coronary intervention.

The authors of the Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation (DEFINE-FLAIR) and iFR Versus FFR in Patients With Stable Angina Pectoris or Acute Coronary Syndrome (iFR-SWEDEHEART) randomized, clinical trials compared iFR to FFR in clinical decision-making for patients with coronary artery disease and intermediate-severity lesions. With instantaneous wave-free ratio (iFR), clinicians use a coronary pressure wire, similar to that used for FFR, to interrogate stenoses with a hyperemia-free (without adenosine) algorithm. Escaned et al used the combined data set from these two trials (4,486 patients total) to examine patients who deferred intervention based on the results of their invasive physiologic testing.

In the combined groups, 2,130 patients deferred PCI based on FFR values > 0.80 or iFR values > 0.89. Deferrals accounted for 50% of the iFR group and 45% of the FFR group. Of these, 1,675 patients presented with stable angina, while the remaining 440 patients had presented with acute coronary syndrome (ACS). Fewer lesions were deferred among patients with ACS compared to those presenting with stable angina (36% vs. 50%; P < 0.001).

Among deferred patients, major adverse cardiac events (MACE) at one year occurred in 46 of 1,117 patients in the iFR group and in 41 of 1,013 patients in the FFR group. Urgent revascularization accounted for most MACE events, occurring in approximately 3% of each group. Presentation with ACS was associated with a higher MACE rate compared to stable angina in deferred patients (5.91% vs. 3.64% in ACS and stable angina, respectively; hazard ratio, 0.61; 95% confidence interval, 0.38-0.99; P = 0.04).

The authors concluded that both iFR and FFR led to safe deferral of revascularization, with a low one-year MACE rate. Patients presenting with ACS experienced a higher event rate compared to those with stable angina.


It is a common misperception that the primary role of invasive physiologic tests such as iFR and FFR is to determine which lesions should be intervened on. The more important role of this technology is to demonstrate which lesions are not hemodynamically significant and should be managed medically.

The Escaned et al study included data from two large randomized studies, was performed with up-to-date techniques and devices, and featured highly complete data collection. The historical DEFER trial, on which much of current practice is based, included only 92 patients randomized to medical management. Escaned et al included more than 2,000 such patients. Understanding the expected hazards for patients going forward can be important. A 4% MACE rate for patients with a negative FFR or iFR is a good fact to know. Even for the ACS population, for which MACE was closer to 6% in the Escaned et al study, these data are reassuring, and support the concept of invasive physiologic testing to guide deferral of intervention.