A large trial in the use of fractional flow reserve to guide percutaneous coronary intervention in patients with stable coronary disease has been halted because of the benefit shown in the patients who received the intervention.
The data safety and monitoring board of the FAME II trial recommended stopping the study early based on the positive results of an interim analysis. The board found a highly statistically significant reduction in hospital readmission and urgent revascularization in stable coronary disease patients who received a stent based on fractional flow reserve (FFR) assessment, compared with those treated with optimal drug therapy, and determined it would be unethical to continue to randomize patients to optimal medical therapy (OMT) based on the results so far, St. Jude Medical announced Jan. 18 in a statement.
The coordinating clinical investigator for the trial, Dr. Bernard De Bruyne, considered this a practice-changing step. The results show FFR "should be considered the standard of care for patients with coronary artery disease."
"What we observed to date regarding urgent revascularizations validates the profound role that FFR-guided therapy has in improving patient outcomes," Dr. De Bruyne, coordinating clinical investigator for the trial and a cardiologist at Onze-Lieve-Vrouw Clinic, Aalst, Belgium, said in St. Jude’s statement.
"[FFR] should be considered the standard of care for patients with coronary artery disease."
But such sweeping statements are premature, according to Dr. Eric Bates, professor of internal medicine at the University of Michigan Health System in Ann Arbor. "The data need to be reviewed by the scientific community."
In FAME II, just over 1,200 patients had been randomized to either FFR-guided percutaneous coronary intervention or OMT in the trial, originally designed for 1,600 patients. Investigators will continue to follow enrolled patients, but no new patients will be added to the trial.
The devices used in the trial, the PressureWire Aeris and PressureWire Certus, combine measurements of pressure and temperature, enabling calculations of fractional flow reserve, coronary flow reserve, and an index of microcirculatory resistance.
The original FAME (Fractional Flow Reserve vs. Angiography for Guiding PCI in Patients with Multivessel Coronary Artery Disease) trial studied the procedure in patients who had already been selected for PCI. In that, patients whose PCI was guided by FFR had significantly reduced rates of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year, compared with those guided by angiography alone (N. Engl. J. Med. 2009;360:213-24). But the FAME II study, begun in 2010, is evaluating use of the tool for improving the benefits of stenting in the first place as an alternative to noninvasive medical therapy.
The latest PCI guidelines from the American College of Cardiology Foundation and the American Heart Association give FFR a tepid class IIa recommendation, saying it is reasonable for assessing angiographic intermediate coronary lesions (50%-70% diameter stenosis) and for guiding revascularization decisions in patients with stable ischemic heart disease (J. Am. Coll. Cardiol. 2011;58 [doi:10.1016/j.jacc.2011.08.007]). According to Dr. Bates, who was vice chair of the writing committee, fewer than 10% of PCI patients undergo FFR.
"Interestingly, there was no difference in death or MI rates" in St. Jude’s statement, "and no mention that the registered primary end point in clinicaltrials.org was the composite of death, MI, and unplanned hospitalization leading to urgent revascularization," he said in an interview. Without the data to examine, the conclusions that it is "unethical to randomize patients to OMT alone" and that FFR has a "profound role" are at the very least hyperbole. "Moreover, the mechanism for decreasing hospital readmission and urgent revascularization rates needs to be explained to me," he added.
Yet, "adding a functional assessment to anatomic data makes great sense and is clinically encouraged." To that end, the ISCHEMIA trial will soon start randomizing 8,000 patients with a LVEF of 35% or more and at least 10% cardiac ischemia. They will undergo blinded computed tomographic angiography to rule out high-risk left main disease or normal coronary arteries, and then will be randomized to catheterization and revascularization plus OMT or to optimal medical management alone, with revascularization reserved for worsening symptoms. The primary end point will be time to cardiovascular death or nonfatal MI*. Secondary end points will include cost effectiveness and quality of life measures.
Dr. Bates had no relevant disclosures.
David Filmore of "The Gray Sheet" contributed to this report. Cardiology News and "The Gray Sheet" are both owned by Elsevier.
*Correction, 1/25/2012: An earlier version of this story listed an incorrect primary end point for the ISCHEMIA trial.