April 05, 2011

April 5, 2011 (New Orleans, Louisiana) — A novel everolimus-eluting stent containing a new metallic alloy, platinum, as part of a modified design has been shown to be noninferior to the widely used Xience V stent (Abbott Vascular)--also known as Promus (Boston Scientific)--in a pivotal trial, PLATINUM, presented during a late-breaking clinical-trials session here today at the American College of Cardiology 2011 Scientific Sessions and published simultaneously in the Journal of the American College of Cardiology [1].

Presenting the data, Dr Gregg Stone (Columbia University Medical Center, NY) said the Xience V stent, a cobalt-chromium everolimus-eluting stent, "has set the current benchmark for patient outcomes, with the lowest reported rates of both stent thrombosis and restenosis." The PLATINUM trial has now shown that this new stent can deliver "comparable clinical outcomes," he said.

"The bar is set very high now," observed panel member Dr Charles J Davidson (Northwestern University Feinberg School of Medicine, Chicago, IL), on hearing the results. He wondered how it was going to be possible to continue to demonstrate clinical advantages of newer and newer stents, when there are likely only minor differences between them. Stone agreed, commenting that what will be important is how the "subtle differences" are deciphered. "There are ways we can continue to improve, but this will require larger trials, with long follow-up, in high-risk patients such as those with ACS, STEMI, and left main."

Moderator of the press conference, Dr Edward J McNulty (University of California, San Francisco), who observed that he had no conflicts of interest and therefore no allegiance to one company or another, agreed: "Our procedures continue to get safer; our equipment and devices are getting better. New stents will have to be as safe as approved devices, and when it comes to deciding which stent is better than another, it will come down to nuanced aspects, and these don't come to light until you are using these devices in lots and lots of people, not in these small trials designed for regulatory approval. This is the sort of information you get from large registries and from feedback from operators."

New Stent Equivalent to Old: "Extraordinary" Low Rate of Adverse Events

The new platinum stent is manufactured by Boston Scientific and is known as Promus Element in markets where it is already approved, which includes the European Union, where it received a CE Mark in 2009. The company says it anticipates FDA approval for the Promus Element stent in mid-2012 [2]. Boston Scientific also has a paclitaxel-eluting stent employing a new platinum-chromium alloy, ION (Taxus Element), which performed well in the PERSEUS trial, which was given CE Mark approval last year and is expected to gain FDA approval by the middle of this year.

When it comes to deciding which stent is better than another, it will come down to nuanced aspects, and these don't come to light until you are using these devices in lot and lots of people.

Promus Element has the same drug, everolimus, and polymer as the Xience V, but the inclusion of platinum instead of cobalt in the scaffolding is designed to make the stent easier to use, including the fact that it is thought to be more flexible, with less chance of recoil, and is more radiopaque and therefore easier to see, said Stone.

Stone reported the 12-month results from PLATINUM, which is a five-year trial. In it, 1530 patients undergoing PCI in one or two of their coronary arteries between January and September 2009 at 132 sites worldwide were randomized to either the new platinum stent (n=768) or the cobalt stent (n=762) as a control. Follow-up was clinical only, said Stone, and the primary end point was the 12-month rate of target lesion failure (TLF): a composite of target-vessel–related cardiac death, target-vessel–related MI, or ischemia-driven target lesion revascularization (TLR), in the per-protocol population.

The new platinum stent was noninferior to the control stent: the primary end points were 3.4% and 2.9% in the two groups, respectively (p for noninferiority=0.001; p for superiority=0.60). There were no significant differences between the two in other safety and efficacy measures, including stent thrombosis, which occurred in just 0.4% of patients in each group, and TLR, which occurred in 1.9% of participants in both arms of the trial. Overall, only 3.3% of the study population had adverse events, a figure that Stone dubbed "quite extraordinary."

The only differences observed, said Stone, were in the need for bailout, which was slightly lower with the platinum stent, possibly due to "ease of use and stability" of the newer product, he said, and also the maximal pressures required with the balloons, which was "slightly higher" with the new platinum stent.

Dr Martin Leon (Columbia University) who earlier presented the findings of the RESOLUTE US study with another novel stent, the Resolute zotarolimus-eluting stent (Medtronic), commented that Stone had demonstrated "the first step with PLATINUM, a different stent platform," but acknowledged that it is "difficult to distinguish some of these devices when the safety and efficacy appear to be at benchmark levels.

"So how do you choose?" Leon wondered. "It’s like anything else in life. When you get up in the morning, do you choose a black jacket or a gray jacket? You don't look for a randomized trial. You've got some very good devices that may have subtle differences that may appeal to one individual or another, but it's going to be difficult to distinguish these devices as being meaningfully different."

Stone serves on the scientific advisory boards for and receives honoraria from Boston Scientific and Abbott Vascular and is a consultant to Medtronic. Davidson receives consulting fees from Abbott Vascular and research grants from Edwards.