Medical Device Daily Washington Editor

The world of medical practice might never run out of controversy, and drug-eluting stents (DES) have fed the controversy machine more than any other medical device in recent memory.

Hardly quieting any arguments, an article in the Jan. 24 edition of the New England Journal of Medicine once again is critical of DES use, not in comparison to bare-metal stents (BMS) this time, but in comparison with coronary artery bypass grafting (CABG) procedures.

According to the authors, a team led by Edward Hannan, PhD, professor of health policy at the University of Albany (Albany, New York), CABG “continues to be associated with lower mortality rates than does treatment with drug-eluting stents” for patients with multi-vessel disease, and CABG is “also associated with lower rates of death or myocardial infarction and repeat revascularization.” Despite these assertions, the article probably offers little real clarity in the DES vs. CABG debate.

The data favor CABG, the authors say, but information toward the end of the article suggests that this conclusion is not absolutely conclusive.

One of the drawbacks to the study is that it was based on data from two registries, the Cardiac Surgery Reporting System and the Percutaneous Coronary Intervention Reporting System, both run by the New York State Department of Health.

But the use of registry data has been the bane of several previous studies of DES compared to BMS, the conclusions from registries often later amended or discredited.

The registry data came from more than 17,000 patients who had a procedure between Oct. 1, 2003, and Dec. 31, 2004, and the mean follow-up times were 19.1 months for the CABG patients, and 18.7 months for those receiving stents.

The patient population was older in the CABG group, on average, “although more patients over 80 years of age were treated with stents than with CABG,” the article says, which is perhaps predicated by the lower tolerance for trauma among the very elderly.

The article says that the data sets include BMS as well as DES. While there is no discussion of the brands of DES included in the registry data, the only DES referred to in the bibliography is the Taxus, made by Boston Scientific (Natick, Massachusetts).

One must read several pages into the article to get to the qualifications of the authors’ conclusions.

The authors state that the major findings of the study are for patients with two- and three-vessel disease, and adjusted rates of death and infarction were significantly lower for CABG.

But “for the mortality outcome, there were no significant differences between drug-eluting stents and CABG for patients with three-vessel disease.”

However, “there was a trend in favor of CABG.”

The results were also rather equivocal for three groups of high-risk patients (diabetics, patients with left ventricular ejection fractions below 40%, and patients 80 years and older), the data indicating “no significant differences in adjusted mortality.”

The authors acknowledge that the use of registry data does not allow the analysis to control for the possibility that a patient “would have been deemed ineligible for one of the procedures” due to health problems. They also say that the data would be more robust with a longer follow-up.

The article also does not discuss comparisons of peri-procedural mortality for the two procedures, which can be of substantial importance.

According to Villareal, et al, in the spring 2002 edition of the Texas Heart Institute Journal, an analysis of data from the institute showed that “in-hospital mortality was significantly greater in patients undergoing CABG than in those undergoing stenting” by 3.6% in the CABG group vs. 0.75% in the stenting group.

The market for bypass surgery has contracted over the past few years as the relative cost of percutaneous interventions have fallen compared to bypass and as angioplasty/stenting gained in popularity.

According to data from the Hospital Cost and Utilization Project (HCUP), sponsored by the Agency for Healthcare Research and Quality, bypass procedures in the U.S. dropped by a third between 1997 and 2005, and angioplasties doubled in frequency from 1993 to 2005 (Medical Device Daily, Sept. 4, 2007).

Part of the fuel feeding the uptake of percutaneous procedures is that many bypass patients cannot withstand a second such operation, in part because scar tissue behind the sternum makes a second procedure much more onerous than the first.

But DES has suffered over the past two years with reports citing increased rates of thrombosis, and greater risk of death from DES-related thrombosis.

Another key event in the fortunes of DES devices is likely to take place next week, when the UK’s National Institute for Health and Clinical Excellence reports the conclusions from its study of the relative value of DES vs. BMS.

Last year, the agency reported that a study of data from two registries of British patients indicated that the cost of a DES for each quality-adjusted life year was too high for the Institute’s appetite, and should NICE formalize this view, sales of DES in the UK and in other parts of Europe — which often follow the Brits’ lead — could fall.

According to a Jan. 23 report by Reuters, the effect could be a 5% reduction in sales this year in Europe.

In an editorial accompanying the NEJM article, Joseph P. Carrozza, MD, writes that while the registry data are “a sobering reality check for those who hoped the benefits of drug elution would level the playing field between CABG and stents,” the data do not show how treatment selection is influenced by co-morbidities.

The Hannan paper, according to Carrozza, also suffers from the fact that “patients were enrolled before widespread use of extended dual antiplatelet therapy as prophylaxis against late-stent thrombosis” and from the fact that follow-up times “capture the majority of clinical events related to the major hazards of stenting — thrombosis and restenosis — but does not include events driven by atherosclerosis of saphenous-vein grafts, a process that begins several years after surgery.”

Hannan did not return calls for comment.