CREST-2 Triggers Spirited Debate on Merits of CAS vs. CEA

The question of whether the CREST-2 trial is a worthwhile use of resources was debated in a didactic session yesterday. The study, which is currently recruiting patients, is comprised of two parallel trials evaluating carotid endarterectomy (CEA) and carotid artery stenting (CAS), each compared with optimal medical therapy alone in patients with asymptomatic, high-grade carotid stenosis.   

‘A bad trial’ 

Leading off his argument that CREST-2 is “a bad trial,” D. Christopher Metzger, MD, FSCAI, FACC, of Wellmont CVA Heart Institute, in Kingsport, Tenn., pointed out that results for CAS are improving over time. He added that the strategy provides excellent patency and stroke prevention out to 4 years, yields low periprocedural major stroke rates and has performed comparably to CEA in North American randomized controlled trials. CAS has been studied in more than 50,000 patients with carotid stenosis of 70% to 80%, he added. Thus, Metzger questioned the rationale for carrying out another CAS vs. CEA trial.

He also expressed concerns about whether CREST-2 is “fair,” highlighting issues surrounding the primary endpoint (the proportion of patients who experienced any stroke or death within 44 days or ipsilateral ischemic stroke out to 4 years) and the distinction between major and minor strokes, the potential inclusion of lower-risk patients and the lack of experienced CAS operators participating in the trial.

Metzger predicted that the trial will enroll slowly and involve many crossovers between groups. “You’re going to have poor buy-in from folks who know how well a carotid stent does in the true obstructive lesions and instead it’s going to be performed by low-volume operators in a study, which in my mind, is biased against carotid stenting,” he said. He added that adoption of CAS is “being held hostage” while the field awaits the CREST-2 results. “I’m not opposed to CREST-2 if we enroll the right patients,” he said. “What I’m opposed to greatly is the fact that everything else has been shut down, so we have to do this trial.”

Trial is a necessity 

Arguing that CREST-2 is necessary, the trial’s co-investigator Gary S. Roubin, MD, PhD, of Cardiovascular Associates of the Southeast, in Birmingham, Ala., noted the strong opinion among neurologists and some vascular surgeons that optimal medical therapy has reduced the stroke rate so low in asymptomatic patients with severe carotid stenosis that CEA and CAS should not be used in this population. CREST-2 is being conducted because the neurology community believes that medical therapy prevents stroke, “and we have to live with that,” Roubin said. “So we can stand by and be critical, or we can participate and ensure that the trial methodology provides a fair comparison.”

For the trial to have credibility, he said, young patients with truly high-grade stenosis and ideal anatomy must be included, skilled operators must participate and a protocol-driven optimal stenting technique is required. Furthermore, mistakes from past trials, such as the inclusion of elderly patients with bad anatomy and moderate stenosis, must be avoided, Roubin added.

“We must manage and control this trial,” he said, adding that he is asking for help with appropriate patient selection in the stent arm, operator credentialing and limiting crossovers. He told the audience that successful completion of CREST-2 will provide high-level scientific data about which asymptomatic patients need revascularization, how the procedures should be performed, and who should be performing them. “We’ll get all that information from the CREST-2 trial,” he insisted.

However, Roubin faced a skeptical crowd. When he took an informal vote about whether CREST-2 is a good idea, only a few audience members raised their hands.

Disclosures: 

• Metzger reports receiving consultant/honoraria fees from Abbott Vascular, Bard, Boston Scientific Corporation, CSI, Spectranetics and TriVascular and serving as a board member for Vascular Interventional Advances (VIVA).  
• Roubin reports equity/royalty/intellectual property rights relationships with Cook Medical, Essential Medical and The Medicines Company.