Will Stenting Replace Endarterectomy for Carotid-Artery Disease?

Will Stenting Replace Endarterectomy for Carotid-Artery Disease?

by David W. Sharp

WHAT'S HOT IN MEDICINE
Rank	Paper	Citations This Period (May-Jun 06)	Rank Last Period (Mar-Apr 06)
1	T.J. Lynch, et al., "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib," New Engl. J. Med., 350(21): 2129-39, 20 May 2004. [Harvard Med. Sch., Boston, MA; Harvard Sch. Public Health, Boston, MA] *821XM	102	1
2	H. Hurwitz, et al., "Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer," New Engl. J. Med., 350(23): 2335-42, 3 June 2004. [9 U.S. institutions] *825JY	91	2
3	J.G. Paez, et al., *"EGFR* mutations in lung cancer: Correlation with clinical response to gefitinib therapy,"** Science, 304(5676): 1497-1500, 4 June 2004. [7 U.S. and Japanese institutions] *825YR	82	3
4	A.A. Hedley, et al., "Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002," JAMA-J. Am. Med. Assoc., 291(23): 2847-50, 16 June 2004. [Ctrs. Dis. Control & Prevent., Atlanta, GA and Hyattsville, MD; U. Calif., Berkeley] *828GT	65	5
5	S. Yusuf, et al., "Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study," Lancet, 364(9438): 937-52, 11-17 September 2004. [Program office: Population Health Res. Inst., Hamilton, Ont. Canada] *853MF	43	†
6	D. Cunningham, et al., "Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer," New Engl. J. Med., 351(4): 337-45, 22 July 2004. [9 institutions worldwide] *839RC	42	6
7	W. Pao, et al., "EGF receptor gene mutations are common in lung cancers from ‘never smokers’ and are associated with sensitivity of tumors to gefitinib and erlotinib," Proc. Natl. Acad. Sci. USA, 101(36): 13306-11, 7 September 2004. [Mem. Sloan-Kettering Cancer Ctr., New York, NY; Washington U. Sch. Med., St. Louis, MO] *853AT	41	†
8	R.S. Bresalier, et al., "Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial," 352(11): 1092-1102, 17 March 2005. [8 institutions worldwide] *906PU	41	9
9	J.S. Yadav, et al. (for the SAPPHIRE Investigators), "Protected carotid-artery stenting versus endarterectomy in high-risk patients," New Engl. J. Med., 351(15): 1493-1501, 7 October 2004. [13 U.S. institutions] *859UP	40	†
10	F.A. Shepherd, et al., "Erlotinib in previously treated non-small-cell lung cancer," New Engl. J. Med., 353(2): 123-32, July 2005. [15 institutions worldwide] *944OP	40	†
SOURCE: Thomson Scientific's Hot Papers Database. Read the Legend.

he Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy trial (SAPPHIRE) has been widely debated, so it is not surprising to see its 2004 publication gaining entry into the Top Ten (#9). Our carotid arteries are susceptible to plaque formation, narrowing, and development of clots. Carefully executed clinical trials have demonstrated the place of endarterectomy. Recent years have seen interest in another intervention, carotid-artery stenting. But stents are no good if they collapse, and the procedure is risky if it produces debris that can be carried further into the cerebral vasculature. In SAPPHIRE, a nickel-titanium alloy stent was used together with a tiny basket which was passed beyond the lesion and removed, along with any wandering emboli, after the procedure. This is the "protection" referred to.

The "high risk" means that all patients had at least one complicating factor such as age above 80 years or clinically significant heart disease. This was a randomized comparison of stenting and endarterectomy so all patients had to be eligible for both approaches. However, more than half the patients enrolled could not be randomized because the surgeons reckoned that endarterectomy would not be safe for them. The reverse situation, with stenting contraindicated when the surgeons were happy with endarterectomy, was unusual. In early 2002 enrollment into SAPPHIRE slowed down and the trial was terminated. However, its object was not to prove that one procedure was better than the other but to show that stenting was not appreciably worse, and this turned out to be the case. The primary endpoint was recorded in 12.2% of patients assigned to stenting and in 20.1% of those assigned to endarterectomy, figures that are compatible with non-inferiority (p = 0.004).

This is a "pivotal study," according to the New England Journal of Medicine’s U.S. editorialist Dr. Richard P. Cambria (New Engl. J. Med., 351[15]: 1565-7, 2004), but he also notes that debate over the SAPPHIRE trial started as soon as the findings began to be presented at scientific meetings in 2003. That discussion continues—for example, the critical analysis by Dr. D.J. Thomas from St. Mary’s Hospital, London, U.K., in which he warns that these data do not constitute "a license for the widespread use of stenting" (Stroke, 36: 912-6, 2005). Both commentators note the problem with the large number of non-randomized patients, and another shared concern relates to the difference between patients whose carotid-artery stenosis is causing symptoms and those in whom it is not. As Thomas points out, medical therapy has advanced since those trials, and an asymptomatic patient might well expect a much lower risk of peri-procedural complications than that recorded in SAPPHIRE before deciding on this intervention rather than conservative (i.e., medical) therapy.

So SAPPHIRE is an important study but one carrying the danger of overenthusiastic interpretation. Other studies are in progress. One from this year also concludes that embolization-protected stenting is not inferior to endarterectomy in high-risk patients (W.A. Gray, et al., J. Vasc. Surg., 44[2]: 258-68, 2006). As with endarterectomy so with stenting, there is no substitute for multiple comparative trials followed by overall assessment of the evidence. In 2005 a Cochrane systematic review concluded that the evidence "to support a widespread change in clinical practice away from recommending carotid endarterectomy" was insufficient (L.J. Coward, et al., Stroke, 36[4]: 905-11, 2005). As Science Watch went to press, the Stent-Supported Percutaneous Angioplasty of the Coronary Artery versus Endarterectomy trial was published (The SPACE Collaborative Group, Lancet, 368: 129-47, 2006). This time non-inferiority of stenting was not proved, a result that, according to the journal’s commentator (A.R. Naylor, Lancet, 368: 1215-6, 2006), provides surgeons and stenters "with evidence to support their own personal prejudices."

Mr. David W. Sharp, M.A. (Cambridge) is contributing editor,
The Lancet, London, U.K.


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Science Watch^®, November/December 2006, Vol. 17, No. 6
Citing URL: http://www.sciencewatch.com/nov-dec2006/sw_nov-dec2006_page5.htm