COURAGE, FAME: Revascularization More Effective Than OMT

MIAMI BEACH, FLA.—The results of the COURAGE and FAME trials demonstrate that revascularization is more effective in reducing ischemia than optimal medical therapy, according to Dean J. Kereiakes, MD, of Ohio State University. During a presentation at the DES Summit here, Kereiakes said that there are several requirements to achieve successful revascularization by PCI for durable relief of ischemia.

Accomplishments of ‘suboptimal PCI’ in COURAGE

In 2007, Kereiakes wrote an editorial on the “truth and consequences” of the COURAGE trial, published in the Journal of the American College of Cardiology. At TCT 2012, he defended his premise that COURAGE “had an unrealistic hypothesis, inadequate statistical power, subject selection bias and exorbitant crossover from medical therapy to PCI.” In addition, he said that PCI in COURAGE was “inadequate, incomplete and suboptimal.”

Of the 1,149 patients randomly assigned to PCI in COURAGE, the procedure was not attempted in 46 and the guidewire did not cross any lesions in 27, Kereiakes said. Additionally, 69% though only 36% of patients received two or more stents, of patients had two- or three-vessel disease, yielding incomplete revascularization among 47% of patients with multivessel disease.

“We know that incomplete revascularization by PCI, even in the absence of CTO [chronic total occlusion], is a powerful predictor of death and MI, and incomplete revascularization by PCI predicts MACE and unplanned revascularization,” he said.

Additionally, DES were used in very few patients in COURAGE. In a meta-analysis published in Circulation in 2009 comparing DES with BMS, the data demonstrated no difference in mortality between the two stent types, although data from observational studies demonstrated a 20% to 25% reduction in mortality in favor of DES. In addition, all studies showed a 50% to 70% reduction in target vessel revascularization (TVR), Kereiakes said.

In a nuclear substudy of the BASKET trial, DES was proven superior to BMS in durable relief of ischemia in target vessel distribution at 6 months (see Figure).

“Alas, all DES may not be created equal,” Kereiakes said. “In a meta-analysis of 13 randomized controlled clinical trials of 17,097 patients, stent thrombosis, TVR and MI were all consistently reduced by Xience’s Promus DES compared with non-EES DES.”

FAME, FAME 2

Kereiakes summarized the results of FAME: FFR ischemia guidance of PCI compared with angiography significantly reduced MACE (P=.02) as well as death and MI (P=.04) in patients with stenosis >50%. In addition, FFR-guided PCI was highly cost effective, numerically reducing revascularization at 2 years compared with angiography, he added.

The results likely reflect the distribution of DES by strategy randomization, which was similar for angiography and FFR, Kereiakes said. Endeavor (Medtronic, 40%), Taxus (Boston Scientific, 40%) and Cypher (Cordis, 20%) were the most commonly employed stents in the FAME trial.

A propensity-matched analysis of the NY State Registry comparing patients treated with Xience/Promus and Endeavor showed no difference in death or MI out to 2 years follow-up, but there was a significant reduction in target lesion revascularization and TVR with Xience/Promus. However, Kereiakes noted that the use of Xience/Promus in FAME would likely not have changed the main observation, and would not have resulted in a difference in death or MI.

The results of FAME 2, which demonstrated that PCI was associated with a highly significant reduction in MACE events, “likely reflect that 88% of patients received treatment with a highly effective second- or third-generation DES, including Promus, Resolute (Medtronic) and Biomatrix (Biosensors International),” Kereiakes said.

“Complete revascularization with contemporary technology (EES) in appropriately selected patients (FFR) will improve the magnitude and durability of ischemia reduction (angina relief; reduction; death/MI) following PCI plus OMT vs. OMT alone,” he concluded.