An article by Steve Syre in today’s Boston Globe – “Bleeding stent sales” (and picked up by DeviceTalk) noted the rather precipitous decline in drug-eluting stent sales during the past year.  J+J, for example, reported a drop of 41% in the second quarter of this year alone.  Two things: (1) this reversal of fortune was predicted last year in a series of articles in this blog and (2) this further validates the concept of drug-eluting stents as being a “transitional” technology.

Steve Syre’s title “Bleeding stent sales” is about as pithy as it gets.  The problem – as anyone who has been following the sector knows – is the small, but significant rate of in-stent thrombosis over the long-term that has been seen with drug-eluting stents (DES).  To put it in lay terms, basically the region around the stent remains, for reasons not entirely known, somewhat unstable and prone to clotting up (thrombosis).  Such an adverse effect is very serious and, in fact, not uncommonly fatal.

Problems with drug-eluting stents predicted last year

A series of articles last year highlighted this safety problem and when put in context with the increasing importance of safety in general (not just with DES but across-the-board in pharmaceuticals and medical devices), a “triple storm” was developing that significantly put at risk the growth projections for the DES market.  In fact, as the Boston Globe article highlighted, there has been a decline in sales for several of the current DES manufacturers.  Those articles can be found at:

The Future of Drug-Eluting Stents: A Big Issue or a Non-Issue? (26 June 2006)

Drug-Eluting Stent Market: $5 Billion Turning on a Dime (24 July 2006)

Drug-Eluting Stents, Part One: Triple Storm Catching Industry Attention (27 November 2006)

Drug-Eluting Stents, Part Two: Triple Storm Catching Industry Attention (28 November 2006)

The upshot is that the current decline in DES sales should not be a surprise, given that drug-eluting stents are essentially serve to improve quality-of-life, and that in this regard safety issues become increasingly relevant in terms of outcomes and patient benefit.

Drug-eluting stents as a Quality-of-Life measure

It has been demonstrated that drug-eluting stents are highly effective in preventing “restenosis” (or a gradually narrowing of the artery) after the initial angioplasty and stent implantation.  It should be noted however, that restenosis affects a patient’s quality of life by causing pain and often requiring a repeat procedure (revascularization). Because of this, it should not be surprising to learn that drug-eluting stents actually have not been shown to improve survival (e.g. save lives) relative to bare-metal stents. Hence DES is essentially a treatment that improves quality-of-life.

In-stent thrombosis is a problem

The effectiveness of drug-eluting stents is based on their generalized inhibition of the repair process at the angioplasty/stenting site.  Even though this effect is localized to the site, the therapeutic effect is relatively crude, essentially leaving an “open wound” in the artery. It should not be surprising to learn that this drug-eluting stent site is prone to in-stent, delayed thrombosis (clotting). While the incidence of this thrombosis is very rare (estimated at less than 0.5 percent to 1.0 percent), it does generally carry with it a 50 percent rate of mortality.   In short: drug-eluting stents have a very small but definitely serious (e.g. fatal) risk of adverse effects

Anti-thrombotic therapy required

To mitigate the in-stent thrombosis problem, nearly all patients on drug-eluting stents are placed on anti-thrombotic therapy (such as Plavix/clopidogrel).  As with all medicines, plavix itself has adverse effects (some of which such as internal bleeding are quite serious and even potentially fatal ).  At approximately $100 per month, there is also a significant cost to the regimen and with the requirement for frequent physician visits, blood tests and monitoring some detriment to quality of life. For many patients, particularly those in which cost and/or compliance are a problem or those in developing countries, all this can represent a significant burden.  Hence, the requirement to be on anti-thrombotic therapy has two consequences. First, it masks the actual rate of life-threatening in-stent thrombosis, which without such ongoing treatment would certainly be much higher. Second, it mitigates some of the quality-of-life improvement afforded by these stents.

The bottom-line is that drug-eluting stents are essentially a “transitional technology” and as such are likely be replaced by other technologies over the coming years.  The challenge is that a $5B industry is not easily reversed despite the indications of retrenchment written about in the Boston Globe article.  However, based on historical market shifts (as outlined in the article “DES Market: $5 Billion Turning on a Dime”) such shifts are not unprecedented, especially if a disruptive technology comes along.  Stay tuned …

Ogan Gurel, MD MPhil
gurel@aesisgroup.com
http://blog.aesisgroup.com/

Convergent Medical Technology Convergent Medical Technologies Combination Medical Products Aesis Research Group Ogan Gurel, MD