CHICAGO — Take a basic stent, add a polymer, add a drug. Do short-term trials with short-term endpoints. Win approval, add the required extra cost and promote it as the next big thing. But don’t say much about follow-on drug regimen, meaning additional cost to patient (and possible low patient compliance). Stir in socio-economic issues — primarily government reimbursement, private insurance, no insurance. And what have you got?

The recipe for a growing debate and still unanswered questions.

At a Monday panel at this year’s annual scientific sessions of the American Heart Association (Dallas), the debate over concerns about drug-eluting stent (DES) technology was characterized by more light than heat, with participants basically agreeing that the issues are complex and considerable research still needs to be done.

But an emerging view seemed to be that the benefits of the DES over their bare metals stent (BMS) brethren are less than originally advertised and that DES devices aren’t best for all patients — certainly not supporting the overwhelming procedural penetration of the stent market to 80% to 90% or more.

Rather tellingly, the debate tended to include renewed attention to the complex factors of cost.

Arguing the benefits and general safety of DES side was David Williams, MD, of Rhode Island Hospital (Providence), reporting on a comparison of 3,000 patients in the National Heart, Lung, and Blood Institute Dynamic Registry who received either DES or BMS. Though DES patients tended to have more complex disease, they had lower rates of mortality in-hospital and at one year. Heart attack was slightly higher in the DES group, but DES patients required less repeat revascularization. And the researchers supported use of DES “in standard clinical practice.”

Presenting the anti-DES position, Joseph Muhlestein, MD, professor of medicine at the University of Utah and director of research at LDS Hospital (Salt Lake City), reviewed a three-year comparison of the Cypher and Taxus stents, the two that are FDA-approved and the focus of the debate. That comparison showed an “all-cause” rate of death higher in DES patients than BMS and a greater rate of adverse events, such as heart attacks, and repeat revascularization procedures out to three years.

It found that the need for target lesion revascularization was lower in DES patients at six months, but that this benefit was lost by three years. Additionally, after three years, all forms of revascularization were higher in the DES patients, due to the need for interventions performed on artery segments not treated in the initial procedure.

DES “may contribute to acceleration of atherosclerosis in other vessels,” Muhlestein said. And he hypothesized that the use of DES had some impact on the “endothelial function” of vasculature adjacent to the treatment area.

In summary statements, Williams stuck by his belief that the broad general use of DES is supportable, but Muhlestein offered what seems to be an emerging consensus: that DES use has been overly aggressive and that there needs to be more focused attempts to match the right stent to the appropriate patient/disease type.

Perhaps the most revealing entry to the debate was made by Netherlands researchers, their study presented by Joost Daemen, MD, clinical research fellow at Thorax Center, Erasmus Medial Center (Rotterdam, the Netherlands).

This study indicated the early success of DES over BMS but later equivalency of the two in 505 patients with ST-segment elevation myocardial infarctions (STEMI), severe heart attack caused by a sudden, total blockage of an artery, treated with stents.

At three years, target vessel revascularization rates were lower with both the Cypher (8%) and Taxus (7.7%) DES devices than BMS (12%), but thrombosis was slightly higher in the DES groups over BMS (total 2.4% in all patients).

And after three years, the rates of heart attack and death were comparable: 16.6% for BMS, 14.6% for the Cypher DES and 16.9% for the Taxus, “suggesting a sustained safety of both drug-eluting devices,” according to the researchers.

While Cordis (Miami, Florida), makers of the Cypher stent, will be happy to banner the heart attack/death data as better than the Taxus from Boston Scientific (Natick, Massachusetts), the larger point would appear to be that the big benefits of DES over BMS that the makers of DES devices were so happy to promote appear to evaporate over time.

The study shows that arteries treated with DES devices need fewer revascularization procedures early on, but more revascularization is needed in the DES-treated patients longer term.

And it will be interesting to see if the overall equivalency of the stent types, long-term, will have any impact on this market — that is, in shifting it back to more BMS use?

An even more important issue, of course, is whether even longer-term studies — out to five, 10 and 20 years — show sustained equivalency of the two stent technologies. Or will DES-implanted patients show increasing need for revascularization and show more adverse events? And what about newer generations of DES set to come online?

The debate was complicated by a fourth member of the panel who presented a study indicating economic disparities in the use of DES and BMS.

John Kao, MD, assistant professor of medicine at the University of Illinois (Chicago), reported that uninsured patients and those covered by the governmental plans of Medicare and Medicaid were more likely to receive the less expensive BMS devices, and patients covered by private insurance more often received DES.

This conclusion was drawn from data showing 4,322 patients receiving BMS devices, 109,693 that had been treated with percutaneous coronary intervention and DES.

The panelists suggested that this disparity represented more than economic bias. Rather, they noted the economic reality that DES-implanted patients required a lengthy follow-on regimen of anti-platelet drugs — inordinately expensive at up to $4 a day over up to 18 months.

And they further noted the clinical implications of such a regimen: frequent non-compliance — because of “cost or ignorance” or other intervening medical procedures, Muhelstein said — and the possibility that this non-compliance may result in a large number of adverse events among DES-implanted patients.

BMS or DES?

Complicated indeed.