Biotech Values

[bridgeofsighs]

Concerning Xience from the Lancet.
http://www.tctmd.com/show.aspx?id=88288
Ouch!
Researchers Find No Need for Taxus Liberté COMPAREd with Xience V
Key Points:

* Xience V safer, more effective than Taxus Liberté
* Results indicate Taxus should no longer be used in everyday practice, investigators say
* Trial a reminder that there is no class effect of DES

By Caitlin E. Cox
Friday, January 08, 2010

A large randomized trial of unselected patients has definitively shown that everolimus-eluting stents provide superior safety and efficacy over paclitaxel-eluting stents, according to a paper published online January 7, 2010, in the Lancet. The results demand an immediate change in clinical practice, the researchers say.

Findings from the COMPARE trial, led by Pieter Cornelis Smits, MD, of Maasstad Ziekenhuis (Rotterdam, the Netherlands), were previously presented in September 2009 at the annual TCT symposium in San Francisco, CA.

For the study, 1,800 consecutive patients undergoing elective or emergent PCI at a single center were randomly assigned to receive either everolimus-eluting Xience V stents (Abbott Vascular, Santa Clara, CA) or paclitaxel-eluting Taxus Liberté stents (Boston Scientific, Natick, MA). There were no limitations involving the number of lesions or vessels, location of lesions, or lesion length.

The incidence of the primary endpoint—a composite of safety and efficacy outcomes including all-cause mortality, MI, and TVR within 1 year—was significantly lower with Xience than with Taxus, primarily due to decreased MI and TVR rates. The secondary endpoint of combined cardiac death, non-fatal MI, and TLR also favored Xience. Moreover, definite and probable stent thrombosis rates were higher at 1 year with Taxus, a finding that reached statistical significance mainly because of a disparity in early stent thrombosis cases between the 2 stents

“On the basis of our results,” the investigators conclude, “we suggest that paclitaxel-eluting stents should no longer be used in daily practice.”

Clear Message for Clinicians

In an e-mail communication with TCTMD, Dr. Smits said he thinks it is important for interventionalists to act on these results since COMPARE treated all-comers and clearly showed the superiority of Xience vs. Taxus. “Of course, we need to await a longer follow-up period [to know for sure],” he said. “However, in the meantime we have stopped using Taxus stents, now that we believe we have a better and safer stent available.”

Based on COMPARE, it appears there are no exceptions to this rule. “Although our subgroup analysis was limited, we did not find [any] subgroup in which Taxus Liberté showed a better trend in outcome compared to Xience V,” added Dr. Smits.

No Class Effect of DES

David E. Kandzari, MD, of the Scripps Clinic (La Jolla, CA), pointed out to TCTMD that even as evidence has accumulated against Taxus in recent years, some interventionalists have continued to use the device. “Maybe clinicians just hit a wall where they don’t want to look at the data anymore,” he noted, adding that the Lancet paper may finally inspire change. “When we get to this point where it’s that stark of a message, maybe it will have an impact.”

Dr. Kandzari noted how trial design has evolved to include longer-term follow-up and larger patient cohorts. “[W]e now have studies highlighting, I think, fairly consistent differences in safety and/or efficacy outcomes between the 2 drug-eluting stent types,” he said. The current study “really underscores what I hope many clinicians had really acknowledged all along, at least to themselves, and that is that there is really no class effect of drug-eluting stents.”

“I think we’re also entering into what many clinicians have described as a period of ‘data fatigue,’” he continued, proposing that the solution is to look at overall themes in the literature for DES outcomes.

“We can challenge and criticize the nuances of the COMPARE trial design and how it was conducted,” Dr. Kandzari acknowledged, highlighting its single-center design and the way certain outcomes were measured. In particular, stent thrombosis rates were reported by investigators rather than determined by a core lab, and periprocedural MI rates only reflected cardiac enzymes captured post-procedure in patients with angiographically apparent complications.

Even so, the study findings are in line with themes apparent in other contemporary trials, he said, adding, “It’s just that the themes are no longer as subtle when, with this manuscript, the primary conclusion by the authors is to not use a particular drug-eluting stent.”

“I’m anxious to see if the conclusions of the SPIRIT IV trial, wherever they may be published, are as stark as they are for this trial in the Lancet,” he added. “From a practitioner’s perspective, I really respect the [COMPARE] authors for making such statements based on their experience and their opinion of their data.”