Royal Philips announced that a combined total of more than 5,000 patients have been enrolled in three prospective clinical studies to assess the safety of deferring cardiovascular interventions using Philips Volcano’s proprietary iFR (instant wave-Free Ratio) pressure measurement technology versus conventional FFR (Fractional Flow Reserve) measurements.
During catheterization procedures to assess and treat a patient’s coronary arteries, a guide wire is used to obtain measurements of the blood pressure at specific points inside the affected arteries to help assess the severity of the blockage(s).
There is a growing body of clinical evidence that the use of FFR in conjunction with interventional X-ray helps improve procedure outcomes, and reduces healthcare costs.
FFR and iFR both measure the difference in blood pressure (and by inference the blood flow) through a partially blocked coronary artery (stenosis) to assess whether the blockage is likely to cause a shortage of oxygen to the heart muscle (myocardial ischemia). Both measurements are performed with the aid of a guide wire-based pressure sensor inserted into the appropriate artery via a small incision in the patient’s leg.
They differ in that FFR measurements require the injection of a hyperemic agent to dilate the artery, whereas iFR’s ability to synchronize pressure measurements to a ‘wave-free’ period in the patient’s heartbeat means that no hyperemic agent is needed. By eliminating the need for hyperemic agents, iFR offers the benefits of reduced procedure time, cost and complexity.
The combination of these three studies represent one of the largest intra-coronary physiologic data sets ever collected. With more than 5,000 patients studied, all with physiologic guidance, it is more than twice the size of the combined enrollment of the DEFER, FAME and FAME 2 studies which shaped the field of coronary physiology.
Further, with nearly 40% of the patients in these studies presenting with Acute Coronary Syndrome (ACS), these studies have the potential to expand the use of physiology above its predominant use today.
Two of the studies, DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization, NCT02053038) and iFR SWEDEHEART (NCT02166736), will assess whether patient outcomes at one year differ when guided by iFR or FFR.
The third study, SYTNAX II (NCT02015832), will evaluate the relative treatment outcomes of a hybrid iFR/FFR strategy coupled with intravascular ultrasound (IVUS) guidance, to compare the clinical utility of percutaneous coronary intervention (PCI) versus bypass surgery for three-vessel coronary disease. More details on these studies can be found below.
Today, many interventional cardiologists using iFR employ a hybrid method for the evaluation of ischemia. When iFR measurements fall within an intermediate ‘gray zone’ (typically 7% to 14% pressure drop) they are followed up with an FFR measurement for confirmation. Clinical trials are needed to establish widely adopted clinical guidelines for iFR that are compatible with current FFR guidelines, in order to widen the use of iFR as a primary diagnostic tool.
"We are all really excited about completing enrollment for the DEFINE-FLAIR, iFR SWEDEHEART and SYNTAX II studies," said Professor Patrick W.J.C. Serruys, DEFINE-FLAIR Study Chairman and SYNTAX II Steering Committee Chairman, Erasmus MC, Rotterdam, the Netherlands. "Together, these three major clinical outcome studies will more than double the randomized published physiology data, and have the potential to re-shape revascularization guidelines and help physicians perform PCI procedures more likely to benefit their patients."
"The combination of these studies adds to the wealth of already published prospective physiology outcome data and may help expand the adoption of iFR, which is already used in over 3,000 cath labs worldwide. Additionally, the nearly 2,000 patients with ACS significantly add to the evidence on physiologic assessment in this type of condition, and may be able to help physicians determine the most appropriate treatment and improve patient care," stated Andrew Tochterman, Segment Leader Image Guided Therapy Devices at Philips.
Featuring harmonized endpoints for a combined total of over 4,500 enrolled patients, the DEFINE-FLAIR and iFR SWEDEHEART studies represent the largest prospective physiological study dataset for iFR technology so far. The 2,500 DEFINE-FLAIR patients were recruited at over 47 centers located across Europe, Asia, North America and Africa.
The 2,043 iFR SWEDEHEART patient enrollees were selected from 15 sites in Sweden, Denmark and Iceland. Importantly, nearly 40% of the patients enrolled in these two studies presented with ACS, making these combined data sets some of the largest ever generated for iFR or FFR in ACS patients. The investigators expect to present the 12-month primary outcome data (myocardial infarction, unplanned revascularization, death) during Spring 2017.
The third study, SYTNAX II, will evaluate the relative treatment outcomes of a hybrid iFR/FFR strategy, along with IVUS guidance, to compare the clinical utility of PCI versus bypass surgery for three-vessel coronary disease using a clinical SYNTAX scoring methodology. SYNTAX II has enrolled 453 multi-vessel disease patients at 22 European sites, and uses contemporary interventional practice combining ischemia-driven revascularization using physiological guidance, the Synergy stent, and IVUS guidance.
Sponsors for the three studies are Imperial College London for DEFINE-FLAIR; Uppsala Clinical Research Center (UCR) for iFR SWEDEHEART; and the European Cardiovascular Research Institute (ECRI) for SYNTAX II. Philips contributes funding and other support for these pivotal studies.