The deployment of drug-eluting stents, such as the Endeavor stent from Medtronic, may be on the rise again. (Source: Medtronic)

The utilization of drug-eluting stents may be poised for a comeback based on recent clinical studies that found they have value despite some risks. Industry analysts, however, suggest that there their usage has plateaued and they can not maintain their initial groundbreaking sales.

While studies have emerged over the past year concerning drug-eluting stents (DES), a few analyses and trials have been particularly influential in adversely affecting the stents’ utilization rates. A spate of negative outcomes—sensationalized by the mainstream press and/or taken to heart by cardiologists—have since been contradicted through extended investigation, further analyses, or paradoxical trial outcomes. This trend may solidly position DES to regain some of the market losses they endured over the past year.

DES were originally brought to the market to retard in-stent restenosis, which occurs in about 10 percent of DES cases compared to 40 percent of bare metal stent (BMS) cases, according to Venkat Rajan, medical device industry analyst for Frost & Sullivan, a San-Diego based market research firm.

Despite the low price and easy reimbursement for BMS, they hold a small percent of the market. In 2006, 300,000 BMS were deployed in the United States, compared to 1.2 million DES. Last year, the number of DES deployments in the States dipped by approximately 100,000, acording to Rajan. While recent positive clinical outcomes have initiated a shift toward greater DES utilization, analysts say the “peak” years may be over.


SCAAR Registry

In February 2007, Lagerqvist et al published three-year results from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) analysis in the New England Journal of Medicine (NEJM). The study included all patients treated with stents in Sweden between 2003 and 2004—6,033 drug-eluting and 13,738 bare metal. Researchers found no difference in the composite of death and myocardial infarction over three years of follow-up. Researchers did find that DES-treated patients had significantly higher adverse event rates (18 percent) after six months, in particular, stent thrombosis, over the follow-up period.

The SCAAR registry results had a devastating effect on the DES market, mainly because of widespread media coverage sensationalizing the apparent increased risk of death with DES.

“At their peak usage rates, DES were being deployed into 90 percent of patients receiving stents in this country. Now it’s as low as 62 percent, said Stephen Ellis, MD, an interventional cardiologist at the Cleveland Clinic.

Because DES immediately achieved its highest potential of 90 percent upon release, the market was bound to endure a downturn at some point, according to Frost and Sullivan’s Rajan.

In Sweden, the home of the SCAAR Registry, the use of drug-eluting stents dropped from 60 percent to 10 percent nearly a year after the initial registry was released, according to a report in the September 2007 NEJM by Stefan K. James, MD, a
SCAAR investigator.

As a result of the negative effects of the registry, the SCAAR investigators extended their study to include more patients. Their latest findings, presented at the 2007 European Society of Cardiology Congress, show no difference between DES and BMS in terms of adverse side-effects when patients are followed out to four years, as opposed to three.

The updated SCAAR study group analysis is based on a one- to four-year follow-up of more than 35,000 patients, who received nearly 62,000 stents: 21,480 patients with only BMS and 13,786 patients who received at least one DES.


Head-to-head

There is some debate regarding individual comparisons of Cypher (Cordis) and Taxus (Boston Scientific), or sirolimus-eluting stents and paclitaxel-eluting stents. Some studies suggest a slight edge for Cypher regarding in-stent restenosis and late stent thrombosis, but the difference seldom comes into play, said Ellis.

The Settler et al meta-analysis, one of the most influential large registries in the last year, examined 38 randomized trials involving 18,023 patients. It compared sirolimus-eluting stents, paclitaxel-eluting stents and BMS to each other. Researchers found that the sirolimus-eluting stents were associated with lower risk of MI during follow-up than paclitaxel-eluting stents and bare metal stents, although mortality rates were similar. The paclitaxel-eluting stents at four years had a late stent thrombosis rate of 2.5 percent, whereas the sirolimus and BMS had nearly identical and slightly lower rates (Lancet 2007;370[9591]:937-948).

Ellis said the Endeavor stent (Medtronic) is not nearly as efficacious as Cypher and Taxus to prevent restenosis and whether it’s safer is debatable.
 

At their height of popularity in 2003, drug-eluting stents were being deployed into 90 percent of patients receiving stents in United States. Today, it’s as low as 62 percent.
Despite the low cost of bare metal stents, cardiologists prefer to use drug-eluting stents because of lower instent restenosis rates.

Safety and efficacy are important issues but these stents also need to prove cost-effective if their usage is to experience an uptick. To drill down to solid cost-effectiveness evidence, one needs to examine the comparator of either medical therapy or BMS, which will produce very different outcomes, according to William Weintraub, MD, chair of cardiology at Christiana Care Health System and director of the Christiana Center for Outcomes Research.

When comparing DES with BMS, researchers should consider the differences in mortality and non-fatal events like MI, of which those differences are slight, Weintraub said. There are, however, differences in revascularizations, and since DES prevent restenosis and therefore prevent further procedures, they are obviously more cost-effective. The only consideration is patient quality of life, which typically involves eliminating angina, and the angina associated with restenosis is short-term.

“At the end of the day, what drug-eluting stents have to be is cheaper. On one side, we are evaluating the cost of current procedures. On the other, we are evaluating the cost of drug-eluting stents. Right now, the difference in cost between the two is minimal, which is good news,” Weintraub said.

While the price of the DES has decreased by about $1000 since they launched in 2003, it is still more than six-times that of BMS. Cypher and Taxus each cost approximately $2000. Medtronic’s Endeavor, the newest FDA-approved DES (February 2008), is expected to cost less than its two predecessors. While the Endeavor may be priced slightly less to ease the product into the market, the difference will not be drastic, according to Rajan.

Depending on the institution, either the administration or the interventional cardiologists decide which DES to use. When choosing a particular brand of DES, administrators take cost into consideration far more than cardiologists, who are more concerned with efficacy, Ellis said.

In the cases where the cardiologist has the choice, they typically make the decision based on an individual patient needs, according to Ellis. Most hospitals offer the choice to their cardiologists of all the stents, even though, some hospitals, like the VA hospitals, may only present one option due to their agreement with a particular stent maker.

At Ellis’s institution, the administrators chose a particular DES, which he and his fellow cardiologists lobbied to change. They were successful.

As more DES come to market, costs are likely to drop even further, creating a situation where DES are actually cost-saving, Weintraub said. The utilization of DES in favor of BMS produces two clear winners: patients, who have less restenosis and less additional procedures, and stent makers, who profit from the sales. Hospitals, however, are losers because they operate under fairly low margins, which can be tipped over into the red fairly easily. For one, the Diagnosis-Related Group (DRG) does not make up for the added cost of DES, and second, hospitals lose revenue from less follow-up procedures, a result of the success of DES.


It takes courage

In comparing DES to optimal medical therapy, the COURAGE trial, which appeared in NEJM in March 2007, found that for patients with stable coronary artery disease, PCI was found to not be cost-effective as an initial management strategy. Weintraub, who was part of the COURAGE trial, noted that the results do not mean that PCI should not be done, but as an initial strategy in chronic stable coronary disease, medical therapy should be attempted. If the patients continue to have angina, then a procedure might be necessary, he said.

Many cardiologists and other cardiology personnel accused the mainstream media of exaggerating the negative clinical outcomes associated with DES trials, and therefore driving down the usage of DES.

“The negative results often grab the headlines, while the follow-up studies disproving the negative results don’t receive nearly enough attention,” Ellis said.

He said the average interventional cardiologist has become more current and less fearful about using DES more often, but perhaps not the case with referring physicians.

On the other hand, Rajan predicted that the market has plateaued, and DES will never achieve their initial popularity. He does not project that the market will decline any further, because the aging population and the obesity problem in the U.S. will demand these life-saving devices.

The coming year will determine how the U.S. drug-eluting stent market will fare, which is always vulnerable to results of ongoing trials. However, now that the market has a third contender in Medtronic’s Endeavor, with a probable fourth in Abbott’s Xience, the cardiologists will have more choices. Finally, with clinical results trending toward the positive, the future is looking bright for this market.