TCT2008回顾：非适应症指征数量与DES置入后MACE率相关

By TCT Daily Staff
The risk of major adverse cardiac events increases in step-wise fashion with each additional off-label indication in patients implanted with drug-eluting stents, according to findings presented at TCT 2008 in Washington, DC.

Anders M. Galloe, MD,?and colleagues from various sites throughout Denmark analyzed data from the SORT OUT II trial to evaluate how off-label implantation of the two drug-eluting stents (sirolimus- or paclitaxel-eluting) used in the trial correlate with the rate of major adverse cardiac events (MACE).

They found that patients with characteristics not included in the FDA-approved indications for the two stents had a significantly higher risk of MACE compared with cases in which the stents were used only for on-label indications.
"The major implication is that a simple counting of the number of off-label indications may enable you to predict the risk of [major adverse cardiac events] within a certain time span," Galloe said in an interview. "If the risk is high, you may prefer a drug-eluting stent to a bare-metal stent and you may extend the duration of dual antiplatelet therapy, thereby individually [tailoring] the assigned adjunctive therapy."

The correlation between the number of off-label indications and MACE increased in a stepwise manner, the researchers found. The incidence of MACE was 25.4% for patients with at least five off-label indications vs. 11.9% for patients with no off-label characteristics (P<.04).

Data from SORT OUT II trial
The SORT OUT II trial, published in the?Journal of the American Medical Association?earlier this year, included 2,098 patients implanted with either sirolimus- or paclitaxel-eluting stents with 1.5 to 3.5 years of follow-up. Galloe said he is not aware of previous studies that investigated MACE in relation to the number of off-label characteristics in the same manner as the SORT OUT II trial.

"The SORT OUT II study is big enough to answer the key question: Is there a correlation between the number of off-label indications for uses of drug-eluting stents in a single individual and the rate of [major adverse coronary events]?" Galloe said. "It is a surprise to see that [each] off-label indication for the use of drug-eluting stents tends to add on to the . . . rate."

He urged physicians to be aware of this fact during patient selection for stent implantation. The more off-label characteristics a patient has, the greater the potential need for a subsequent drug-eluting stent or prolonged antiplatelet therapy, if appropriate, Galloe said.

The SORT OUT II data enabled the researchers to account for 19 different off-label characteristics, he said. Once their research is published, "other scientists may perform a new analysis for these off-label indications and calculate the [major adverse cardiac event] rates in order to verify our results in other settings," he said.

One limitation of the analysis is that some of the sample sizes are small once the SORT OUT II population is divided into subpopulations. The researchers said they plan to follow the patients for up to five years to continue to document any adverse events.

"Some of the sample sizes are small, and statistical power diminished, which [might have been] partly compensated for by our waiting for the [MACE] rates to keep on increasing, thereby enabling further analysis of stent thrombosis, coronary death, acute MI, and other secondary endpoints," Galloe said.