A host of studies unveiled this summer comparing the drug-eluting stents (DES) of Boston Scientific (Natick, Massachusetts) and the Cordis (Miami Lakes, Florida) unit of Johnson & Johnson (J&J; New Brunswick, New Jersey) have added to the confusion over which device-drug combination is better suited for the treatment of coronary artery disease and the prevention of in-stent restenosis.
Several studies in mid-August editions of the New England Journal of Medicine (NEJM) and the Journal of the American Medical Association (JAMA) appear to give the edge to Cordis’ Cypher sirolimus-eluting stent, while another study published in the Aug. 1 issue of the American Journal of Cardiology (AJC) gives the nod to Boston Sci’s Taxus paclitaxel-eluting stent. Currently, the two devices are the only DES products approved for sale in the U.S.
Both the NEJM and JAMA studies were randomized, head-to-head comparisons of the Cypher and Taxus stents and examined complex patient groups, including patients with diabetes. Data from the randomized, head to head Sirolimus-eluting and Paclitaxel-eluting Stents for Coronary Revascularization (SIRTAX) study and the Paclitaxel-eluting and Sirolimus-eluting stents to Prevent Restenosis in Diabetic Patients (ISAR-DIABETES) studies, as well as a meta-analysis of six, randomized head-to-head studies of the two drug-eluting stents, appeared to show improved outcomes with use of the Cypher stent vs. the Taxus system.
The SIRTAX study, a 1,012-patient comparison of the devices, included not only patients with angina but also a large percentage of patients who were suffering from an acute myocardial infarction at the time of the stent placement. In that study, the use of the Cypher as compared with the Taxus resulted in significantly fewer major adverse cardiac events (6.2% vs.10.8%), primarily by significantly decreasing the need for target lesion revascularizations (TVRs) (4.8% vs. 8.3 %).
ISAR-DIABETES, a study of 250 patients with diabetes and coronary artery disease, found that the use of the Cypher is associated with a marked decrease in the degree of tissue in-growth into the segment that received the stent as compared with use of the Taxus stent (late lumen loss 0.43 mm vs. 0.67 mm), with a resulting significant reduction in restenosis (6.9% and 16.5%). This benefit was observed in both insulin-dependent and non-insulin-dependent diabetics.
“There is a difference,” said David Moliterno, chief of cardiology and co-director of the Gill Heart Institute at the University of Kentucky (Lexington, Kentucky), who wrote an editorial on the studies in the NEJM. “It’s reasonably small, but it is real.”
For all patients taken as a group, Moliterno said, those who receive the Taxus stent seem to be 2% to 3% more likely to need their procedure redone than those who receive the Cypher. For low-risk patients, the choice of stent may not matter, he said – and indeed, some doctors prefer Taxus because it can be easier to get stents into tortuous arteries. However, high-risk patients, such as those with diabetes, may fare better with the Cypher stent, Moliterno said.
The JAMA and NEJM authors said they're not sure why the Cypher stent performed better than the Taxus stent in the trials. The difference could be due to stent design, the mechanisms that enable the drugs to be released from the stents, or the drugs themselves. “Other unidentified factors may as well be responsible for the observed difference in performance between the two stents,” authors of the JAMA study wrote.
None of these articles offered new research. The JAMA article and the NEJM editorial focused on statistical compilationS of previous clinical trials. Two other NEJM articles described clinical trial results that had been presented at medical conferences - results from the SIRTAX and ISAR-DIABETES trials were presented at the American College of Cardiology (Bethesda, Maryland) annual meeting in Orlando in March.
In JAMA, the authors concluded that Cypher had a lower rate of restenosis (9.3% vs. 13.1%) and a lower rate of TVR (5.1% vs. 7.8%). The rates of death, heart attack and stent-related blood clots were statistically similar for both stents. In the JAMA article, researchers looked at six clinical trials involving 3,669 patients, conducting a statistical examination, known as meta-analysis, to integrate the data from several studies. The eight JAMA authors are affiliated with medical institutions in Germany, Spain and Switzerland. Although two have received research grants or lecture fees from some U.S. companies, they haven't received any payments from either J&J or Boston Scientific, they said.
The NEJM editorial added that overall data suggest that Cypher provides a “clinical edge,” but that Taxus “holds an edge on availability, deliverability and cost.” In calling for a more definitive comparison, Moliterno noted that some of the tests that he reviewed “have limitations that affect the reliability of their findings.” In two of the tests, for example, he said “the number of patients tested was moderate,” with each clinical trial conducted at only two study centers. He added that the testing of second-generation stents and stent delivery systems “is already well under way.”
In a statement, Boston Scientific argued that most of the data in the new analyses are not up to the level that medical societies would demand for making treatment decisions – and that there is still no clear difference between the two stents. A company spokesperson noted that the largest trial to date comparing the two devices, the 1,353-patient REALITY trial – which was funded by Cordis – failed to prove a benefit for the Cypher over Taxus. It missed its primary endpoint of a significant reduction in eight-month binary restenosis. Cypher produced a rate of 9.6% vs. 11.1% for Taxus.
Also bolstering Boston Sci’s arguments that there truly is no clear winner yet was the contradictory study in the American Journal of Cardiology, which showed that Boston Sci’s Taxus Express2 system had lower incidents of major adverse cardiac events (MACE) than the Cypher system. The study showed a safety trend in favor of Taxus over Cypher in the cumulative one-year MACE rate, the study’s primary endpoint, which was 15.6% for Taxus vs. 20.4% for Cypher. Of the three MACE components, the results favored Taxus over Cypher in the cumulative rates of TVR (5.9% for Taxus vs. 10.3% for Cypher) and myocardial infarction (10% for Taxus vs. 14.1% for Cypher). For the third component, cumulative mortality, the results were essentially equivalent (7.2% for Taxus vs. 7.7% for Cypher).
“The major finding of this study is that unrestricted use of PESs [paclitaxel-eluting stents] in a universal drug-eluting stent environment is associated with a nonsignificantly lower incidence of major adverse cardiac events at one year compared with SESs [sirolimus-eluting stents],” authors of the AJC study wrote. The study, conducted at the Rotterdam Cardiology Hospital (Rotterdam, the Netherlands), included 293 patients with diabetes and de novo coronary artery disease who were enrolled in identical sequential registries, one assessing the paclitaxel-eluting stents and one assessing the sirolimus-eluting stents.
The authors of the various articles say additional research is needed in order to make a better comparison. “Our finding needs to be confirmed by longer follow-up studies,” said the JAMA authors. “A large-scale randomized trial may help settle this score more definitely,” said an editorial in the NEJM.
Even if J&J were to benefit from the study data, it still is being held back by supply and regulatory issues with its manufacturing facilities. Differences in ease of use for doctors, marketing and, especially, supply and manufacturing, may prevent Cypher from retaking the market lead that it enjoyed prior to the introduction of the Taxus stent. J&J said that the FDA has visited new manufacturing plants that would finally allow it to churn out more Cypher stents – and the company is waiting for the nod to start the assembly lines running.