Everolimus-eluting stents are superior to paclitaxel-eluting stents, and the latter should no longer be used in everyday clinical practice. That’s the conclusion of the COMPARE investigators in a report published online in the Lancet. But at least one expert in the field, David Kandzari, thinks the conclusion, though justified by the data, goes beyond the simple binary choice of choosing one stent over another. (See below for his perspective.)

COMPARE, which was initially presented at TCT last year, compared the everolimus-eluting Xience V stent to the paclitaxel-eluting Taxus Liberté stent in 1800 PCI patients. The primary endpoint (all-cause mortality, MI and TVR) was reached in 6% of the Xience group and 9% of the Taxus group (p=0.02). The difference was attributed to fewer cases of stent thrombosis (1% versus 3%), MI (3% vs 5%), and TVR (2% vs 6%).

David Kandzari sent the following comment to CardioBrief:

COMPARE is one of several recent and well designed trials highlighting what many cardiologists have recognized for some time, namely that there is not a class effect of DES (which was the conclusion from the 12/2006 FDA Panel meeting). When the first competitive DES became available, both the clinical community and industry focused almost exclusively on differences in angiographic restenosis and late loss metrics. Fortunately, as the emphasis returned to patient-focused clinical outcomes, attention then turned to differences in efficacy between DES, which were often inconsistent and influenced by protocol mandated angiographic follow up. Over this time, however, and with dedicated long-term follow up and larger sample sizes, studies began highlighting directly or indirectly comparative differences in safety outcomes. And now, we have several studies indicated safety and/or efficacy differences between existing DES.

The interest to me is that for what seems topical at the time (restenosis, TLR, or now stent thrombosis/MI), we will have trials that identify differences in such endpoints. And, because there are so many trials and of varied design, there is more than just chance probability that we will find unexpected and inconsistent results. So, I believe a key point for clinicians trying to assemble what has been termed ‘data fatigue’, and trying to understand which stent to use for patients, is to look at the broader view of themes for DES. Is there a consistency in the results of COMPARE with other trials? Is there a signal raised for late stent thrombosis with PES in other trials? Do EES have consistently greater efficacy than PES in other trials? The answer to all of these questions is yes.

We can challenge and criticize the nuances of the COMPARE trial design and its conduct, but the themes for each DES are apparent in other contemporary trials as well. It’s just that they’re no longer as subtle when the primary conclusions in a major journal are to not use a particular DES. It’s trials like COMPARE that challenge how we move forward in assuming a ‘one size fits all’ regulatory model of DES approval, what the appropriate comparator DES should be (and what the sample size will be as outcomes are further refined), and ultimately, whether physicians really adhere to the evidence at hand and change their practice.

Here is the press release from the Lancet:

EVEROLIMUS-ELUTING STENT BETTER THAN PACLITAXEL-ELUTING STENT IN UNSELECTED PATIENTS (COMPARE study) (Online First)

The everolimus-eluting stent is better than the second generation paclitaxel-eluting stent in unselected patients undergoing percutaneous coronary intervention (PCI)*in terms of safety and efficacy, concludes the COMPARE study, published Online First (www.thelancet.com) and in an upcoming edition of The Lancet. On the basis these findings, the authors suggest that paclitaxel-eluting stents should no longer be used in everyday clinical practice. The Article is written by Dr Pieter Cornelis Smits, Dr. Elvin Kedhi, and Dr. Eugene McFadden, Department of Cardiology, Maasstad Ziekenhuis, Rotterdam, the Netherlands, and colleagues.

Compared with the currently available first-generation drug-eluting stents, second-generation drug-eluting stents have been designed with the goal of improving safety, efficacy, and device performance. Everolimus, a semisynthetic sirolimus analogue, is released from a thin coating of biocompatible fluoropolymer on an open cell, thin strut, cobalt-chromium frame. A significant reduction in serious adverse cardiac events was noted in patients with the everolimus-eluting stent compared with those who had the first-generation paclitaxel-eluting stent. This first-generation stent has been superseded in Europe by the new-generation paclitaxel-eluting stent since September, 2005. Whether such differences persist with a new-generation paclitaxel-eluting stent that consists of the same polymer but has a different stent platform is not known.

The COMPARE study randomly assigned 1800 consecutive patients (aged 18–85 years) undergoing PCI at one centre to treatment with everolimus-eluting and second-generation paclitaxel-eluting stents. The primary endpoint was a composite of safety and efficacy (all-cause mortality, heart attack, and target vessel revascularisation**) within 12 months.

Follow-up was completed in 1797 patients. The primary endpoint occurred in 56 (6%) patients in the everolimus-eluting stent group versus 82 (9%) in the paclitaxel-eluting stent group (relative risk of primary endpoint occurring was 31% lower for the everolimus group). The difference was attributable to a lower rate of stent thrombosis (6 [<1%] vs 23 [3%]), heart attack (25 [3%] vs 48 [5%]), and target vessel revascularisation (21 [ 2%] vs 54 [6%]). Cardiac death, non-fatal myocardial infarction, or target-lesion revascularisation occurred in 44 [5%] patients in the everolimus-stent group versus 74 [8%] patients in the paclitaxel-stent group.

The authors say: “The use of second-generation everolimus-eluting stents, compared with paclitaxel-eluting stents, was associated with a significant reduction in the risk of major adverse cardiac events at 1 year. This difference was a result of reduction in the rate of myocardial infarction, a safety component of the primary endpoint, and reduction in repeat revascularisation of the target vessel.”

They conclude: “The everolimus-eluting stent is better than the second generation paclitaxel-eluting stent in unselected patients in terms of safety and efficacy. On the basis of our results, we suggest that paclitaxel-eluting stents should no longer be used in everyday clinical practice.”