Medical Device Daily

So far, so good for drug eluting stents (DES) with a biodegradable polymer.

A full year of follow-up with patients receiving the novel stents have shown results comparable, or non-inferior, to stents with permanent polymer coatings in a presentation at the European Society of Cardiology (ESC; Sophia Antipolis, France) meeting being held in Barcelona.

DES have proven effective in preventing the re-narrowing of an artery after it is opened in a percutaneous coronary intervention (PCI) procedure and the market for these devices was estimated at almost $2 billion in the U.S. alone in 2008.

Yet several studies have shown persistent risk of blood clot formation inside DES over a longer time period after implantation than observed with bare metal stents. (Medical Device Daily, Sept. 1, 2009).

Recent angiographic studies have also shown a scar tissue accumulation can be seen up for up to two years after implantation of DES, and further, that the risk of late in-stent blood clot may be caused by a delayed healing process or a persisting inflammatory response to the permanent polymer that controls the drug-release from the surface of stent.

A biodegradable polymer DES specially developed for the Individualized Drug-Eluting Stent System to Abrogate Restenosis (ISAR) project, consists of a sand-blasted, stainless-steel stent coated with a polymer that dissolves over nine weeks.

The ISAR-TEST-4 study then randomized 2,603 patients assigning half to receive the new biodegradable stent and dividing the other half between the Xience DES from Abbott (Abbott Park, Illinois) and the Cypher DES from Cordis (Miami Lakes, Florida), a unit of Johnson & Johnson's (New Brunswick, New Jersey), both of which feature permanent polymer coatings.

The study, an all-comers trial where the cohort were non-selected patients undergoing PCI in de novo native-vessel coronary lesions, was conducted at two tertiary medical centers, the Deutsches Herzzentrum and the Medizinische Klinik of the prestigious Klinikum rechts der Isar, both in Munich, Germany.

The primary endpoint was a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or revascularization related to the target lesion (TLR) at one year.

The results, published online simultaneously in the European Heart Journal, indicate that safety and efficacy outcomes at one year are comparable with those of permanent polymer-based DES.

"These results now provide a framework for testing the potential clinical advantage of biodegradable polymer DES over the medium- to long-term," according to lead investigator Julinda Mehilli, MD, from the Deutsches Herzzentrum.

In a press conference ahead of the presentation, Mehilli told reporters, "At the moment, all I will say is that a bioerodable polymer seems as good as the permanent polymer, and that I need a longer-term follow-up to say that we have better safety with this stent."

"But probably the bioerodable-polymer stent will be the DES of the future," she added.

Abbott expands range of stents and scope of trials

Abbott reported at ESC 2009 the next generation in its family of DES stents, the Xience Prime, is now being widely distributed in European markets, and in select countries throughout Asia-Pacific and Latin America, on the heels of receiving the CE mark in June.

A cobalt chromium stent with what Abbott calls one of the thinnest strut designs available, the Xience Prime is articulated in a broad matrix of sizes, including the SV version for small vessels and the LL version for long lesions.

The Xience Prime also feature greater visibility under x-ray during stent implantation procedures.

These design features "make it easier for a physician to appropriately reach and treat a lesion in complex anatomy," said Patrick Serruys, MD, with the Thoraxcenter at Erasmus University Hospital (Rotterdam, the Netherlands), who is also the editor of EuroIntervention, a publication of the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Abbott also updated European cardiologists on the dizzying series of SPIRIT clinical trials that are designed as head-to-head competitors for the Xience stents, which remain in development and not available for sale, with the market-leading Taxus DES from Boston Scientific (Natick, Massachusetts)

The trials now included SPIRIT II through SPIRIT V and Abbott recently reported the launch of a further trial, SPIRIT PRIME to continue hammering at Taxus. (MDD, June 18, 2009).

Abbott trials have a total participation of some 22,000 patients, and data from the SPIRIT IV trial, one of the largest comparing Xience V to Taxus, will be presented at the Transcatheter Cardiovascular Therapeutics annual meeting later this month in San Francisco.

Double dose of blood thinner reduces stent risks

One study presented at ESC strongly suggests that reducing stent thrombosis and other adverse cardiac events following stent implantation may be as simple as taking a pill, or rather two pills.

Shamir Mehta, MD, with McMaster University (Hamilton, Ontario) delivered reassuring news for cardiologists and great news for the two pharmaceutical companies that manufacture the blood thinner clopidogrel, reporting that doubling the dosage significantly reduced the risks of myocardial infarction (MI) and stent thrombosis for patients.

With 25,087 patients participating, the CURRENT-OASIS 7 trial – clopidogrel optimal loading dose usage to reduce recurrent events/optimal antiplatelet strategy for interventions – is the largest clinical trial aimed at evaluating different dosing regimens for the blood thinner in a broad range of acute coronary syndrome (ACS) patients.

"Virtually every interventional cardiologist is using clopidogrel," Mehta said at the press conference ahead of his presentation.

"After the results of this trial are presented, they will have to decide what to do," he said, predicting that the trial results will require an adjustment to current guidelines for prescribing clopidogrel.

"It's a simple change to institute," said Mehta. "It means going from one pill to two pills a day, with cost implications that are virtually negligible while the benefits are great," improving patient outcomes in PCI.

Among the PCI patients in the study population receiving the higher dose of clopidogrel there was a 15% reduction in the composite endpoint of cardiovascular death, heart attack, or stroke at thirty days.

The major contributor was a 22% reduction in MI and what was called a highly significant 42% reduction in the risk of stent thrombosis, which was a secondary endpoint.

A further finding in the study data revealed that the patient group given a higher dose of aspirin consistently did better.

"There was no downside to using the higher dose aspirin and there may have been a benefit," Mehta reported.

The study was sponsored by Sanofi-Aventis (Paris) and Bristol-Myers Squibb (New York), co-commercialization and co-development partners for clopidogrel under the brand name Plavix.