For more than a year, cardiologists have been discussing emerging evidence that drug eluting stents (DES), as effective as they are at reducing the risk of restenosis, may be more prone than bare metal stents to late problems - namely, late, sudden occlusion of the coronary artery. This phenomenon is seen because DES may inhibit the growth of the normal tissue that, typically, will eventually coat bare metal stents. This normal tissue inhibits blood clotting on the stent. Since this normal coating of tissue may not occur on DES, the risk of sudden clotting is now thought to persist for a long time - perhaps indefinitely - leading to the need for prolonged therapy with clopidogrel (Plavix) in patients treated with DES.
Last week, at the World Congress of Cardiology, researchers presented evidence that patients treated with DES may have an increased long-term risk of poor outcomes, compared to patients treated with bare metal stents. This evidence came from long-term results from the clinical trials that originally gained approval for DES.
In one study, investigators found that patients treated with the sirolimus-eluting stent (Cypher, J & J), had a statistically significant increase in long-term incidence in death or heart attack as compared to patients treated with bare metal stents. Patients treated with paclitaxel-eluting stents (Taxus, Boston Scientific), had a trend toward increased long-term risk, but that trend was not statistically significant. In another meta-analysis using data from 17 randomized trials, on the other hand, there was no difference in cardiac mortality in patients treated with DES vs. bare metal stents, (though, inexplicably, there did appear to be an increase in non-cardiac mortality, such as cancer, stroke or lung disease).
In a presentation of new data derived from the BASKET study, results were were analyzed from the 746 patients treated for more than 6 months, to see whether the incidence of late problems differed among patients treated with DES vs. bare metal stents. They found that there was no overall difference in outcomes between the two groups. However, DES led to somewhat a better outcome when used in small coronary arteries, or in bypass grafts.
Finally, in long-term data presented from the RAVEL trial, the original trial reporting a remarkable decrease in the rate of restenosis with DES, the long-term incidence of death or heart attack was not significantly different between DES and bare metal stents. Indeed, there was a non-significant trend toward better outcomes with the bare metal stent.
In a separate development, the Wall Street Journal reported on September 7 that Boston Scientific had held a meeting with FDA in early August to report a small (0.5%) but statistically significant increase in late occlusion with its Taxus stent. This constitutes the first time a company has acknowledged an increased risk of late thrombosis with DES. J & J, in the same article, while admitting to a similar incidence (0.6%) of late occlusion with its Cypher stent, maintained that their data, as yet, provided no "safety signal."
According to articles posted by Shelley Wood on TheHeart.org (a website for medical professionals, registration required), the presentation of this new evidence at the World Congress led to heated discussion among the cardiologists in attendance. The cardiology community has enthusiastically embraced DES over the past 5 years, and this new evidence that DES may not be superior to bare metal stents in producing favorable long-term outcomes - and may even be detrimental in some - strikes at some fundamental beliefs among heart specialists, who now realize they must grapple with the implications.
(Go to the next page for DrRich's comments on what this new information means to patients with coronary artery disease.)
