Drug-Eluting Stents: A Short-Lived Fall From Grace?

The rapid adoption and use of drug-eluting stents has been followed of late by an unceremonious fall. The first one, Johnson & Johnson’s (J&Js) Cypher, was introduced in October 2002 and launched in April 2003. Boston Scientific’s version, called Taxus, was approved in March 2004. By 2005, these products were racking up combined sales of $3.1 billion. This is a remarkable, perhaps unprecedented, rise but recent questions have caused sales to take a dramatic hit.
 
Stents are implanted during percutaneous coronary interventions (PCIs) to improve blood flow in patients with coronary artery disease. Bare metal stents, a predecessor technology, first became available for this purpose in the 1990s. But they had problems with restenosis, a re-narrowing of the artery after implantation. Based largely on their success in reducing the incidence of restenosis, drug-eluting stents were adopted very rapidly. At the beginning of 2006, drug-eluting stents were being used in 85 percent of all PCIs in the U.S.

Sales Performance Falling

Following their rapid and dramatic rise in popularity, drug-eluting stent sales have taken a dive this year. Sales of J&J’s Cypher, for example, are down 41 percent compared to the same period in 2006, and sales of Boston Scientific’s Taxus have plunged by 42 percent. The fact that sales of both products are down by essentially the same amount while their overall market share has not changed (46 percent for Cypher and 54 percent for Taxus) signals that this is a “category effect” and not restricted to a particular company’s product. And while drug-eluting stents are still used in the majority of PCIs, their penetration rate is now 65 percent — a full 20 percentage points behind where it was a year earlier.

Exacerbating these losses, the total number of PCI procedures fell by 10 percent, from 273,000 in the second quarter of 2006 to 245,000 in the second quarter of 2007. That means drug-eluting stents are being used in smaller numbers in a procedure that’s being performed less frequently.

So What Happened?

Starting in the second half of 2006, several things happened to cause the downturn. These occurred very close together in time, confusing the situation. For the sake of clarity, here’s a brief timeline:

• In September 2006, studies presented at the European Society of Cardiology/World Congress of Cardiology meeting reported potential problems with thrombosis following drug-eluting stents implants;
• In the fall of 2006 and into the winter of 2007, these above-mentioned studies generated significant media attention which, in turn, led to an FDA hearing on the subject and a congressional review of off-label marketing that included drug-eluting stent practices; and
• In March, another study questioned PCIs more generally. Results of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial were presented at the American College of Cardiology and published in the New England Journal of Medicine. The summary states, “As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction or other major cardiovascular events when added to optimal medical therapy.” Although the study doesn’t say it, the conclusion that many physicians drew from COURAGE is that PCIs are not worth the risk involved.

A Turnaround on the Horizon?

Although, manufacturers may not want to panic just yet. Just as a variety of factors fueled the sharp downturn, there are a number of signs that both drug-eluting stents and PCI will regain their lost ground in the not too distant future.

First, the risk of thrombosis that triggered the uproar about drug-eluting stents is low — less than 1 percent per year. And restenosis, the primary reason for using drug-eluting stents in the first place, has not gone away. Evidence that clinicians are remembering this is borne out by stabilization in drug-eluting stent penetration rates which was essentially unchanged at 65 percent of all PCIs throughout the second quarter of 2007.

In another sign that the U.S. market may have initially overreacted, international sales of drug-eluting stents did not experience the same downturn. While international drug-eluting stent sales did fall, J&J and Boston Scientific report a 14 percent drop compared to the more than 40 percent decline in the U.S. Even if we consider that markets outside the U.S. didn’t have quite as far to fall, this is a significant difference.

Sales are a function of how many PCI procedures are performed and the penetration of drug-eluting stents within those procedures. Internationally, the total number of international PCI procedures actually increased by 3.5 percent to reach 414,000 in the second quarter of 2007, so that provides a bit of additional optimistic news on the first point.

Also, the drug-eluting stent pipeline is full with several new products expected to enter the market in the next two years. These include new products from existing players as well as new entrants such as Abbott’s Xience and Medtronic’s Endeavor. These products will offer a wider set of therapeutic options to choose from, and their marketing campaigns are sure to put drug-eluting stents back in the spotlight in a positive way.

PCI Study Problematic

There is also reason to believe the initial fears sparked by the COURAGE trial were misplaced. As noted earlier, the trial compared PCI to drug therapy as an “initial management strategy in patients with stable coronary artery disease.” This is really nothing new, as lifestyle changes and anti-platelet drug therapy have always been the preferred options for initial therapy. The problem is, it is notoriously difficult to get patients to change their lifestyles and not much easier to ensure long-term compliance with drug therapy. And patients with coronary artery disease who have trouble with one or both of these issues eventually wind up needing a PCI.

Within two years, evidence of patient noncompliance combined with a new generation of drug-eluting stents should result in sales spiking back up to their previous levels. The market may grow at a more moderate rate in the future as a result of the FDA bearing down harder on off-label use and more safety verification prior to approval. But then, few markets have ever seen the explosive growth rates drug-eluting stents experienced early on. — Todd Clark