Medical Device Daily Associate

ATLANTA – As the 55th edition of the American College of Cardiology 's (ACC; Bethesda, Maryland) annual scientific sessions wound down this week, one topic that has maintained its momentum within the cardiovascular community for the past several years is that of the drug-eluting stent (DES).

There were literally hundreds of presentations done on these devices during the conference, and many of these studies looked to compare the efficacy of the two drugs thus far being used in these systems, paclitaxel and sirolimus.

Inevitably, the comparisons looked at the two dominant players in the market at this time – Johnson & Johnson (J&J; New Brunswick, New Jersey), which uses sirolimus on its Cypher DES system and Boston Scientific (Natick, Massachusetts), which uses paclitaxel on its Taxus system.

Predictably, both companies claimed victory for specific subsets of patients, though some analysts suggested that they offered little new substance.

“From a competitive point of view, little new ammunition was provided by either JNJ or BSX to change the current market dynamics,“ Morgan Stanley (New York) analyst Glenn Reicin wrote in a note to clients.

One provocative study, discussed at a Tuesday morning press conference, evaluated 5,845 patients who were involved in trials evaluating both of these drugs, finding that sirolimus was superior to paclitaxel. To overcome the limitations of single head-to-head randomized trials, the researchers aimed to compare sirolimus-eluting stents (SES) to paclitaxel-eluting stents (PES) by both direct and indirect meta-analysis.

Researchers at Policlinico San Donato (Milan, Italy), Middelheim Hospital (Antwerp, Belgium) and the Medical College of Virginia (Richmond, Virginia) used the pooled results of 15 independent head-to-head trials to compare the efficacy of SES to PES.

Sirolimus is an immunosuppressive drug, a chemical agent that suppresses the immune response, and paclitaxel is an antineoplastic agent, which inhibits or prevents the growth and spread of malignant cells.

Researchers studied the results for binary angiographic restenosis (BAR) and target lesion revascularization (TLR) in a total of 5,854 patients (2,852 treated with SES and 3,002 treated with PES) at six and 12 months. Results showed significant reduction in BAR (p<0.0001) and TLR (p=0.0008) among patients treated with SES. BAR is a renarrowing of the previously unblocked artery; TLR is a repeat procedure or bypass surgery to unblock a previously repaired artery.

“When we looked at the primary endpoint [BAR] . . . we found that sirolimus-eluting [Cypher stent] was associated with a 38% relative risk reduction in binary restenosis rate,“ said Antonio Abbate, MD, a resident at the Medical College of Virginia , who presented the study results on Tuesday. As for TLR, he said the Cypher showed a 34% relative risk reduction.

The paper concluded that the study establishes the superiority of SES to PES in patients undergoing percutaneous coronary intervention and should be taken into account, together with costs, in clinical decision-making.

“I think the results of this combined meta-analysis is reassuring because we now know that all available data . . . confirms the finding of superiority of sirolimus over paclitaxel,“ attributing this to the “greater anti-proliferative affect of sirolimus.“

However, Abbate cautioned against choosing a DES solely on anti-proliferation, citing other key factors, including stent platform and device cost.

Moderator Spencer King III, MD, chair of interventional cardiology at the Fuqua Heart Center of Piedmont Hospital (Atlanta), warned against inferring that these results translate to a difference in myocardial infarction death or stroke for the two devices, and Abbate conceded that no such differences were found.

King said that the real conclusion should be “that it definitely establishes the superiority of sirolimus-eluting stent in reducing the amount of neointimal proliferation that occurs – that's what you're really measuring here.“

Data from another multicenter, prospective, randomized controlled clinical trial suggests that the Cypher outperformed the Taxus in procedures involving long coronary lesions, some of the most complex blockages to treat via angioplasty.

The LONG DES-II (percutaneous treatment of long native coronary lesions with Drug-Eluting Stents II) compared the angiographic in-segment binary restenosis rate of the Cypher vs. the Taxus at six months, at five centers in Korea and including 500 patients. Lesion length needed to be greater than 25 mm. It is estimated that long lesions such as these comprise about 20% of cases treated by interventional cardiologists today.

“In this study, the Cypher stent showed better outcomes than the Taxus stent in these complex, long lesions. Patients with very long lesions are among the most difficult to treat and tend to be at higher risk of restenosis,“ said Seung-Jung Park, MD, PhD, principal investigator and chief of interventional cardiology, ASAN Medical Center (Seoul, Korea).

In this study, the patients received a mean total stent length of about 41 mm.

Additionally, patients treated with the Cypher had significantly larger minimal in-stent diameter (vessel opening) at follow-up than patients treated with the Taxus; 2.39 plus or minus 0.46 mm for the Cypher Stent vs. 2.04 plus or minus 0.65 for the Taxus, important for blood flow, and a lower average in-stent diameter stenosis than those treated with the Taxus (13 plus or minus 17.8% for the Cypher vs. 23.6 plus or minus 20.7% for the Taxus at late follow-up).

Secondary endpoints included in-segment and in-stent restenosis at six months as well as Major Adverse Cardiac Events (MACE). At the nine-month clinical follow-up, MACE rates were 3% for the Cypher vs. 7.8% for the Taxus.

Not to be outdone, Boston Scientific (Natick, Massachusetts) reported results from the independent, multi-center STENT registry, the largest prospective, comparative real world DES study ever reported, the company said.

The study included follow-up on 5,566 patients at eight coronary centers in the U.S. who received either a Taxus Express2 DES or a Cypher DES, including 1,182 diabetic patients, nearly 500 of whom were insulin-treated diabetics.

Among insulin-treated diabetics, the results demonstrated a numerical trend toward improved survival and lower overall MACE rate for patients who received a Taxus stent system vs. those who received a Cypher stent system.

Among the study's diabetic patients, the Taxus was used in more complex lesions. The Taxus patients had a slightly higher ACC risk score, smaller vessels and longer lesions than Cypher patients. Despite the higher complexity of the Taxus patients, the results favored Taxus over the Cypher in each of the study's MACE categories for insulin-treated diabetics.

In news from other companies at the ACC on the DES front:

• Abbott (Abbott Park, Illinois) reported the first clinical results for its investigational ZoMaxx DES for the treatment of coronary artery disease. A 40-patient, single-arm, clinical, angiographic and intravascular ultrasound (IVUS) trial, ZOMAXX IVUS was conducted in 40 patients, mean age of 59 years.

It demonstrated 100% procedural success, no major adverse cardiac events and minimal late vessel diameter loss during four-month follow-up; 80% of patients had hyperlipidemia (high cholesterol), 40% had diabetes, and 40% had a prior heart attack. The mean lesion length stented was 14.4 mm.

Before treatment with a ZoMaxx stent, percent diameter stenosis was 70%. Directly after treatment, percent diameter stenosis improved to 5.1% inside the stent and 19% in-segment, or within the stent plus 5 mm on either side of it. Late lumen loss was 0.20 mm in-stent and 0.17 mm in-segment.

The ZoMaxx stent was delivered with 100% success, the company said.

• Medtronic (Minneapolis), which is racing to become the third company to sell DES devices in the U.S., said the latest test data showed that its Endeavor compared favorably to the Cypher.

Medtronic said the new data showed its Endeavor stent – using the immunosuppressant drug ABT-578 licensed from Abbott – is safe and effective in treating coronary artery disease after one year, with no statistically significant differences from the Cypher. Medtronic also said combined data from a study called Endeavor III and two earlier studies gave its stent an overall rate of thrombosis, or blood clots, of just 0.3%.

On a key statistic including the number of deaths, heart attacks and repeat procedures in patients, Endeavor's rate was 13.2% after 12 months, vs. 11.8% for Cypher. After nine months, Endeavor's rate was 12%, 11.5% for Cypher.

Last fall, Medtronic suffered a blow when the Endeavor III study narrowly missed its main goal of equivalency with J&J's stent on a measure known as “late loss“ after eight months of patient use, a predictor of whether a heart vessel will re-clog, with the data collected by physically measuring the narrowing of arteries. In this study, however, “late loss“ data were not remeasured.

The company plans to submit data from four Endeavor studies to the FDA to support its application for approval and said it remains on track for a 2007 U.S. market launch. Medtronic already sells the Endeavor in Europe.

Medtronic is also studying its stent's performance against the Taxus stent in the Endeavor IV trial, set for enrollment completion this spring. It said it has enrolled 1,000 of an intended 1,548 patients so far.

No Comments