St. Jude Reports Good News from FAME II Trial

Positive results from the FAME II clinical trial bring an end to the study’s enrollment. The Independent Data Safety Monitoring Board (IDSMB) recommended that the trial, conducted by St. Jude Medical, be stopped because it has found a “highly statistically significant reduction in the need for hospital readmission and urgent revascularization when fractional flow reserve (FFR)-guided assessment was used to direct treatment in patients with coronary artery disease,” according to a release issued by the company.

FFR is a physiological index used to determine the hemodynamic severity of narrowings in the coronary arteries, and is measured using St. Jude Medical’s PressureWire Aeris and PressureWire Certus. FFR specifically identifies which coronary narrowings are responsible for obstructing the flow of blood to a patient’s heart muscle (called ischemia), and guides the interventional cardiologist in determining which lesions warrant stenting, resulting in improved patient outcomes and reduced healthcare costs.

The goal of the trial is to further study the role of FFR in the treatment of stable coronary artery disease by comparing percutaneous coronary intervention (PCI) guided by FFR plus optimal medical therapy (OMT) to OMT alone.

During coronary catheterization, a catheter is inserted into the femoral (groin) or radial arteries (wrist) using a sheath and guidewire. FFR uses a small sensor on the tip of the wire (commonly a transducer) to measure pressure, temperature and flow to determine the exact severity of the lesion. This is done during maximal blood flow (hyperemia), which can be induced by injecting products such as adenosine or papaverine. A pullback of the pressure wire is performed, and pressures are recorded across the vessel.

There is no absolute cut-off point at which FFR becomes abnormal; rather, there is a smooth transition, with a large grey zone of insecurity. In clinical trials however, a cut-off point of 0.75 to 0.80 has been used; higher values indicate a non-significant stenosis, whereas lower values indicate a significant lesion.

The DSMB recommended that St. Jude Medical stop patient enrollment due to increased patient risk of major adverse cardiac events (MACE) among patients randomized to OMT alone compared to patients randomized to OMT plus FFR-guided PCI. In particular, patients receiving OMT alone experienced a highly statistically significant increased risk of hospital readmission and urgent revascularization, and the DSMB determined that this difference was highly unlikely to change with inclusion of more patients, the company reported. 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 PCI plus OMT compared to OMT alone. However, the COURAGE study did not require use of ST. Jude’s 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 ischemia,” said Bernard De Bruyne, M.D., Ph.D., of the OLV Clinic in Aalst, Belgium, and coordinating clinical investigator of the FAME II trial. “What we observed to date regarding urgent revascularizations 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 enroll any new patients. The trial randomized 1,219 patients with stable coronary artery disease in 28 centers in Europe, the United States and Canada.

“The original FAME trial demonstrated that FFR guidance improves outcomes in patients with stable coronary artery disease and two or three vessel disease. Today, FAME II confirms that PCI is beneficial for patients with one, two and three vessel disease whose ischemia has been documented by FFR,” said Frank Callaghan, president of the St. Jude Medical Cardiovascular Division. “Due to the statistically and clinically compelling differences in the number of patients returning to the hospital for an urgent revascularization procedure – which can be considered a surrogate for a repeat heart attack or death – we support the recommendation of the DSMB and the trial’s Steering Committee. We expect the data will continue to reveal the important role that FFR plays in developing an optimal treatment strategy.”

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

The original FAME trial was a randomized, prospective, multi-center trial that enrolled 1,005 patients with multivessel coronary artery disease. The FAME study compared outcomes for patients whose treatment was guided by FFR to those whose treatment was guided only by angiography using St. Jude Medical’s PressureWire Certus technology. The 12-month results, published in the Jan. 15, 2009, issue of the New England Journal of Medicine, demonstrated that instances MACE were reduced by 28 percent for patients whose treatment was guided by FFR rather than by standard angiography alone. Two-year results demonstrated that patients who received FFR-guided treatment continued to experience improved outcomes over time, including a 34 percent reduction in risk of death or heart attack.

St. Jude’s main competition in the FFR space is San Diego, Calif.-based Volcano Corp. Despite the competition in this space, the good news for St. Jude could also be perceived as a good thing for Volcano and its FFR product line.