1、CREST: Safety and Efficacy Similar for Carotid Surgery, Stenting Email Key Points: CREST shows similar safety, efficacy for CAS vs. CEA Data seen as watershed moment for reimbursement Another study favors CEA but leaves CAS option open By L.A. McKeown Friday, February 26, 2010 Long-awaited results f
2、rom a large trial of carotid endarterectomy vs. stenting show that both procedures are equally safe and effective for the treatment of carotid atherosclerosis and the prevention of stroke, myocardial infarction (MI), and death. The results were presented February 26, 2010, at the American Stroke Ass
3、ociations International Stroke Conference 2010 in San Antonio, Texas. CREST (Carotid Revascularization Endarterectomy vs. Stenting Trial) involved 2,502 patients with either symptomatic (n = 1,321) or asymptomatic (n = 1.181) carotid stenosis who were randomized to endarterectomy or carotid stenting
4、 at 117 centers in the United States and Canada over a 9-year period. Patients, who were an average age of 69 years, received neurological exams and best medical therapy and risk factor management. Follow-up was out to 4 years (median 2.5).At a press conference prior to the presentation of the resul
5、ts, CREST investigator Wayne M. Clark, MD, of Oregon Health and Science University (Portland, OR), reported that at 4 years, both procedures were similar with regard to the primary endpoint (composite of any stroke, MI, or death within 30 days plus subsequent ipsilateral stroke) as well as in the ov
6、erall secondary endpoint of periprocedural complications (table 1).Table 1. CREST OutcomesCAS CEA HR (95% CI)Primary Endpoint 4 Yearsa7.2% 6.8% 1.11 (0.81-1.51)Periprocedural Complicationsb5.2% 4.5% 1.18 (0.82-1.68)a Primary Endpoint, any stroke, MI, or death within 30 days plus subsequent ipsilater
7、al stroke.b Periprocedural Complications, any periprocedural stroke, MI, or death.However, stent patients experienced more strokes and fewer MIs in the periprocedural period than did surgery patients (table 2).Table 2. Periprocedural MI and StrokeCEA CAS HR (95% CI) P ValueStroke 2.3% 4.1% 1.79 (1.1
8、4-2.82) 0.01MI 2.3% 1.1% 0.50 (0.26-0.94) 0.03The rate of minor stroke was 2.7% for CAS vs. 1.4% for CEA, and the rate of major stroke was 1.4% for CAS vs. 0.8% for CEA, with neither of the differences achieving statistical significance. The overall death rate was only 0.6%.Dr. Clark and colleagues
9、point out that the rate of stroke and death in the surgical group was the lowest ever reported in a large stroke prevention trial.Moreover, “the rate for stroke and death in carotid stenting was also the lowest yet reported in any randomized trial, and significant advances in technology, technique a
10、nd patient selection for stenting have continued over the 8-year enrollment in CREST,” said Gary Roubin, MD, PhD, of Lenox Hill Heart and Vascular Institute (New York, NY), in a prepared statement. Dr. Roubin is a lead investigator for CREST and the studys co-principal investigator for stenting.Dr.
11、Clark added that at 4-year follow-up, recurrent event rates were low in both groups: 2.0% for CAS, 2.4% for CEA. “So both procedures seem to be very safe,” he said. “Im excited to say I think we have 2 good options to treat patients.”Most Strokes Were Non-DisablingCommenting on the trial, Christophe
12、r J. White, MD, of the Ochsner Heart and Vascular Institute (New Orleans, LA), said while there were more strokes overall in the stenting group, the incidence of major strokes and death between the surgery and stenting groups “was completely a draw.” He further added that the majority of the strokes
13、 were non-disabling, which is an important caveat, especially when discussing treatment options with patients.“Obviously nobody wants to have a stroke, but these were non-disabling strokes involving numbness or weakness that is gone in a few days,” Dr. White said in a telephone interview with TCTMD.
14、 “These are very similar to a surgical cranial nerve palsy, which we see in endarterectomy, where you cant speak or swallow or blink. Yes, its a deficit, but its a minor deficit that typically goes away.”In fact, Dr. Clark pointed out that the rate of cranial nerve palsy in the surgical group was 4.
15、7%, compared with 0.3% in the stented group (P 0.001). “That can maybe cause as much disability as a minor stroke,” he added.Age Differences EmergeIn an interaction analysis, stenting results were slightly better for patients ages 69 and younger, with the benefit increasing with decreasing age. Conv
16、ersely, for patients older than 70, surgical results were slightly superior to stenting, with the benefits increasing along with age.“When we went into this, I think most of us felt that the less invasive procedure would be best suited for the older patient. Now that we have data from studies in the
17、 United States and Europe we have to question that,” said CREST principal investigator Thomas G. Brott, MD, of the Mayo Clinic (Jacksonville, FL), who spoke at the press conference. However, Dr. Brott cautioned that cutoff points for age can be misleading.According to Dr. White, this difference may
18、be due to increased tortuosity of the arteries as people age, which can make it more difficult to place stents. While stenting is not entirely out of the question in the very old, he said the skill level required by the operator is increased.Unlike some prior endarterectomy trials that have shown hi
19、gher rates of death and major stroke in women compared with men who undergo carotid revascularization, CREST found no significant difference between sexes in the primary endpoint.Dr. Brott added that data on medical therapy in both arms of the trials is still being tabulated, but will be important i
20、n the overall analysis of CREST.CREST vs. CMS: Hope Runs HighCurrently, the Centers for Medicare and Medicaid Services (CMS) only reimburse carotid stenting procedures for symptomatic high-risk patients in whom surgery is prohibitive. With the release of the CREST data, some like Dr. White hope CRES
21、T will be the watershed moment clinicians have been waiting for to nudge CMS into finally viewing carotid stenting as a viable alternative to surgery.“What CREST means isnt that stenting should be used in place of surgery, it means that each individual patient and his or her physician can now have a
22、 conversation about which procedure suits them better,” said Dr. White, who is a spokesperson for the Society of Cardiovascular Angiography and Interventions. “Before today, you couldnt have that conversation because there was no agreement on safety and there was no reimbursement from Medicare. The
23、importance of CREST is that not only will it give physicians confidence, it will also give regulators confidence in terms of payment for patients to be able to have this procedure. Right now Medicare forces everyone to have surgery, and I think thats a little unfair.”Dr. Clark said the CREST investi
24、gators are still analyzing cost data, which CMS will likely need to make any decision regarding carotid stenting. In addition, both Drs. Clark and Brott said operator experience and monitoring also will be a factor since CMS included language in the initial coverage decision for stenting that addres
25、sed the need for adequate training and experience.ICSS Gives Edge to SurgeryHours before the CREST results were presented, the Lancet and Lancet Neurology published 2 reports from the International Carotid Stenting Study (ICSS) suggesting that endarterectomy is safer than stenting for patients with
26、symptomatic carotid artery stenosis. Furthermore, they found that stenting triples the occurrence of new ischemic brain lesions on MRI compared with surgery. The studies were published online ahead of print on February 25, 2010.For ICSS, investigators led by Martin M. Brown, MD, of University Colleg
27、e London (London, United Kingdom), assessed the effectiveness of stenting and endarterectomy in preventing stroke, death, and procedure-related MIs in 1,713 patients with recently symptomatic carotid stenosis. Patients were randomly assigned to stenting (n = 855) or surgery (n = 858) and followed fo
28、r up to 120 days after randomization.At 30 days post-treatment, the risk of stroke, death, or periprocedural MI was higher in the stenting group than in the endarterectomy group (7.4% vs. 4.0%; 95% CI 1.1-5.6; RR 1.83, 1.21-2.77, P = 0.003). The incidence of stroke, death, or periprocedural MI was 8
29、.5% in the stenting group vs. 5.2% in the endarterectomy group, representing an estimated 120-day absolute risk difference of 3.3% (95% CI 0.9-5.7) with an HR of 1.69 (1.16-2.45; P = 0.006) in favor of surgery.Risk of any stroke (65 vs. 35 events; HR 1.92; 95% CI 1.27-2.89) and all-cause death (19 v
30、s. 7 events; HR 2.76; 95% CI 1.16-6.56) were higher in the stenting group than in the endarterectomy group. In addition, 3 fatal periprocedural MIs occurred in the stenting group, compared with 4 non-fatal MIs in the endarterectomy group. However, like CREST, there were fewer cases of cranial nerve
31、palsy in the stenting group compared with the endarterectomy group (1 vs. 45) as well as fewer hematomas of any severity (31 vs. 50 events; P = 0.0197).“Our results suggest that carotid endarterectomy should remain the treatment of choice for symptomatic patients with severe carotid stenosis suitabl
32、e for surgery,” Dr. Brown and colleagues write. “Most patients had no complications from either procedure. Thus, some patients might still opt for stenting after being presented with the available evidence, especially if they have a strong preference for avoiding surgery.”The second paper from ICSS
33、involved a substudy of 231 patients (124 from the stenting group and 107 from the surgery group) who underwent preprocedural and postprocedural diffusion-weighted MRI (DWI) to detect new ischemic lesions.New postprocedural lesions occurred more frequently in patients treated with stenting than in th
34、ose treated with endarterectomy (OR 5.21; 95% CI 2.78-9.79; P 0.0001) and an increasing DWI lesion volume was associated with subsequent symptomatic strokes. The authors also found that the incidence of DWI lesions was higher in centers that routinely used embolic protection devices during stenting
35、than in those that did not.The investigators conclude that differences in non-disabling strokes within the ICSS study might not solely be related to differences in clinical follow-up. They point out that most of the new ischemic lesions were not associated with symptoms of stroke at the time of sten
36、ting, suggesting that particles of atheromatous plaque are released during stent implantation. Though too small to cause any noticeable symptoms at the time, this may be significant enough to lead to small areas of brain damage.In an editorial accompanying both studies, Klaus Grschel, MD, of the Uni
37、versity of Gttingen (Gttingen, Germany), suggested that both approaches could serve as treatment options and “should preferably complement each other, with advantages of either technique in certain patient subgroups, which each need to be identified.” He added that DWI, as used by the ICSS investiga
38、tors in the substudy, might detect even subclinical ischemic lesions and should be increasingly used to monitor procedure quality. In addition, he suggested the imaging technique could help identify patients who might benefit from either treatment.ICSS vs. CREST: More Similarities Than Differences?D
39、r. White said that while the conclusions of the ICSS investigators are different than those of the CREST investigators, the results themselves are mainly the same.“ICSS and CREST are very consistent in their findings,” he said. “Both show no difference in major stroke and death between stenting or s
40、urgery.” Dr. White added that the primary outcome measure of ICSS is the 3-year rate of fatal or disabling stroke. Although those data have not yet been analyzed, he said he is fairly certain that “the final analysis of ICSS will be the same as CREST.”But from a scientific standpoint, Dr. White said
41、 he believes CREST comes out on top of ICSS mainly because of the experience of the operators. Unlike ICSS, CREST had a lead-in phase to train less experienced operators prior to the trial. “One of the weaknesses of ICSS is they didnt do that,” he said. “They had some very inexperienced people, and
42、I think they paid the price for that. A fundamental flaw is that there arent enough experienced stenters to conduct these trials, so you have to allow people with relatively little experience to get started, but you also have to build in a buffer that allows for a learning curve. The CREST researche
43、rs should be congratulated for doing that.”Other issues could explain the differences between the 2 trials, according to Dr. White. For example, the ICSS trial included only symptomatic patients, whereas CREST included both those with and without symptoms. In addition, use of embolic protection devi
44、ces in CREST was nearly 98% compared with only about 75% in ICSS.Dr. Clark said that, while he has not carefully reviewed the ICSS results, another factor to consider when weighing the 2 trials is that CREST investigators uniformly used the same stent and the same embolic protection device throughou
45、t the trial, whereas ICSS investigators used multiple stents and had inconsistent use of embolic protection.Sources:1. Brott TG, Roubin G, Howard G, et al. Randomized carotid revascularization endarterectomy vs stenting trial (CREST): Primary results. Presented at: American Stroke Association Intern
46、ational Stroke Conference; February 26, 2010; San Antonio, TX. 2. International Carotid Stenting Study investigators. Efficacy and safety of carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): An interim analysis
47、of a randomised controlled trial. Lancet. 2010;Epub ahead of print. 3. Bonati LH, Jongen LM, Haller S, et al. New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: A substudy of the International Carotid Stenting Study (ICSS). Lancet Neurol. 2010;Epub ahead of print. 4. Grschel K. Has surgery won the race against endovascular treatment for carotid stenosis? Lancet Neurol. 2010;Epub ahead of print. Disclosures:
