Drug-Eluting Stents Significantly Outperform Brachytherapy for In-Stent Restenosis

Martha Kerr

March 21, 2006

March 21, 2006 (Atlanta) -- Two major studies comparing the efficacy of brachytherapy with a drug-eluting stent for in-stent restenosis of a bare-metal stent show that the drug-eluting stents, whether sirolimus-eluting or paclitaxel-eluting, had greatly superior long-term clinical and angiographic outcomes compared with standard care with brachytherapy.

Vascular brachytherapy was the only US Food and Drug Administration-approved treatment for restenosis of a bare-metal stent in a coronary artery at the time of study enrollment. Because the rate of a recurrence of stenosis with radiation is high, and a number of smaller studies using drug-eluting stents showed lower rates of restenosis, the major trials were undertaken.

Results of the 2 trials were reported here at the 55th annual scientific sessions of the American College of Cardiology, coinciding with publication of reports on the trials in the March 15 issue of JAMA.

In the Sirolimus-Eluting Stent for In-Stent Restenois (SIRS) trial, David R. Holmes, Jr, MD, from the Division of Cardiovascular Diseases at the Mayo Clinic in Rochester, Minnesota, and colleagues randomized 384 patients with stenoses of bare-metal stents to 1 of 2 treatment groups: vascular brachytherapy or placement of a sirolimus-eluting stent (SES [ Cypher, Cordis, Inc, Warren, New Jersey]) in the bare-metal stent to open up the coronary artery.

Procedural success was 99.2% in the brachytherapy group and 97.3% in the SES group ( P = .28).
However, at 9-month follow-up, compared with brachytherapy, SES use was associated with significantly lower rates of target vessel failure (21.6% vs 12.4%; P = .020) and target vessel revascularization (19.2% vs 8.5%; P = .004).

At angiographic follow-up, the rate of binary angiographic restenosis was also lower in the SES group than in the brachytherapy group (19.9% vs 29.5%; P = .07).

The minimal lumen diameter after regaining patency was larger with the SES than with brachytherapy ( P < .001), as was the net lumen gain ( P < .001) due to stenting and the lack of edge restenosis.

"This was a home-run for drug-eluting stents," Dr. Holmes told Medscape in an interview. "The restenosis rate with drug-eluting stents is still higher than you would like, but brachytherapy was just not effective," he said.

Further support favoring the use of a drug-eluting stent over brachytherapy was shown by the results of the paclitaxel-eluting Taxus Express stent (Boston Scientific Corp, Natick, Massachusetts) for in-stent restenosis (TAXUS V ISR) trial. Presented by Gregg W. Stone, MD, from Columbia University Medical Center in New York City, he and his colleagues randomized 396 patients with restenosis of bare-metal stents to vascular brachytherapy or a paclitaxel-eluting stent (PES).

At 9-month follow-up, PES compared with brachytherapy reduced the rate of target vessel revascularization by 40% (10.5% vs 17.5%; P = .46) and was associated with a 43% relative risk reduction in the rate of overall major adverse events (11.5% vs 20.1%; P = .02).

PES also reduced the rate of angiographic restenosis at 9 months by 53% (14.5% vs 31.2%; P < .001).

The rates of cardiac death, recurrent myocardial infarction, and target vessel thrombosis were similar in the 2 groups of TAXUS V ISR.

While the data are strong in favor of PES for in-stent restenosis, Dr. Stone cautioned meeting attendees that "there are still safety questions with drug-eluting stents in highly thrombotic environments."

In a JAMA editorial accompanying the SIRS and TAXUS V ISR report, Debaba Mukhurjee, MD, and David J. Moliterno, MD, both from the University of Kentucky, Lexington, write that "the next major question may shift the optimal strategy for in-stent restenosis within bare-metal stents to that occurring in drug-eluting stents. It is doubtful that brachytherapy will have a tenable role" in this setting.

And Dr. Holmes told Medscape, "We will probably no longer be doing brachytherapy in this group," but he added that the availability of drug-eluting stents is not high in many parts of the world," so the question is still relevant for many patients.

Roger Campbell, MD, director of the Cardiac Catheterization Laboratory at Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, echoed Dr. Holmes' caution. "Questions remain with late in-stent thrombosis safety," he told Medcape. "We've proven the efficacy of drug-eluting stents, but safety is the number-one consideration and still debatable."

ACC 55th Annual Scientific Session: Abstract 2402-9, presented March 13, 2006; abstract 2922-69, presented March 14, 2006.

Reviewed by Ariana Del Negro