New FFR trial to stop enrolment following positive interim analysis


An interim analysis of the FAME II trial has found a highly statistically significant reduction in the need for hospital readmission and urgent revascularisation when fractional flow reserve (FFR)-guided assessment was used to direct treatment in patients with coronary artery disease. As a result of the positive interim analysis, the FAME II independent Data Safety Monitoring Board (DSMB) has recommended investigators stop patient enrolment in this trial as the DSMB considers it unethical to continue to randomise patients to optimal medical therapy alone.

FFR is a physiological index used to determine the haemodynamic severity of stenosis in the coronary arteries, and is measured using the PressureWire Aeris and PressureWire Certus from St Jude Medical. FFR specifically identifies which coronary narrowings are responsible for ischaemia, and guides the interventional cardiologist in determining which lesions warrant stenting, resulting in improved patient outcomes and reduced healthcare costs.


The goal of the St Jude Medical sponsored FAME II (Fractional flow reserve-guided percutaneous coronary intervention plus optimal medical treatment vs. optimal medical treatment alone in patients with stable coronary artery disease) trial is to further study the role of FFR in the treatment of stable coronary artery disease by comparing percutaneous coronary intervention guided by FFR plus optimal medical therapy to optimal medical therapy alone.


The DSMB recommended that St Jude Medical stop patient enrolment in its FAME II trial due to increased patient risk of major adverse cardiac events among patients randomised to optimal medical therapy alone compared to patients randomised to optimal medical therapay plus FFR-guided percutaneous coronary intervention. In particular, patients receiving optimal medical therapy alone experienced a highly statistically significant increased risk of hospital readmission and urgent revascularisation, and the DSMB determined that this difference was highly unlikely to change with inclusion of more patients. The data currently reflect no observed difference in the rates of death or heart attack.


The FAME II trial may provide new insights about the benefits of coronary intervention and answer questions raised by the COURAGE (Clinical outcomes utilizing revascularization and aggressive drug evaluation) trial, which demonstrated no difference in the outcomes between percutaneous coronary intervention plus optimal medical therapy compared to optimal medical therapy alone. However, the COURAGE study did not require use of PressureWire FFR measurement technology.


“The FAME II trial is unprecedented in its ability to provide further answers and evidence regarding the optimal way to treat patients with coronary artery disease and myocardial ischaemia,” said Bernard De Bruyne, OLV Clinic, Aalst, Belgium, and coordinating clinical investigator of the FAME II trial. “What we observed to date regarding urgent revascularisations validates the profound role that FFR-guided therapy has in improving patient outcomes. This is further evidence that FFR should be considered the standard of care for patients with coronary artery disease.”


The FAME II trial will continue following patients currently enrolled according to the trial protocol and will not enrol any new patients. The trial randomised 1,219 patients with stable coronary artery disease in 28 centres in Europe, the USA and Canada.


Data will be published as information is analysed, with initial results expected to be presented this year.