September 27, 2010 (Washington, DC) — The latest results for the in-house-coated, polymer-free stent being developed in Munich show that a microporous stent, coated with a combination of drugs and a biocompatible "shellac resin," but no polymer to control elution, can have nearly identical one-year outcomes to that of the Resolute zotarolimus-eluting stent.
Dr Julinda Mehilli (Deutsches Herzzentrum, Munich, Germany) presented the ISAR-TEST 5 results here at TCT 2010.
The ISAR-TEST 5 trial builds on findings from ISAR-TEST 2, previously reported by heartwire . Both studies use the propriety stent-coating technology being codeveloped by the ISAR group, with both sirolimus (rapamycin) and probucol, an antihyperlipidemic drug. As Mehilli explained, probucol is both a good antioxidant and is highly lipophilic, but its primary effects on the vessel appear to be in preventing recoil and remodeling, rather than affecting neointimal hyperplasia.
"Since probucol is more lipophilic than rapamycin, we [speculated that we would] have better release kinetics of the rapamycin from the microporous surface of the stent," she said in a morning press conference. "With our first-generation ISAR polymer-free stent, it had only rapamycin on it and we had a very early, fast release of the drug. . . . Adding probucol to this mixture, we had better release kinetics, with 80% released within six weeks after implantation."
In ISAR-TEST 2, investigators compared their dual-drug, polymer-free stent with the Cypher stent and the first-generation Endeavor zotarolimus-eluting stent, showing restenosis rates in the ISAR dual-drug stent at one year to be similar to the Cypher stent, but significantly lower than those of the Endeavor.
ISAR-TEST 5
This time around, ISAR-TEST 5 compared the ISAR stent with the new zotarolimus-eluting Resolute stent, which uses the BioLinx polymer system and was recently shown to improve on the Endeavor's efficacy. In ISAR-TEST 5, an "all-comers" population of 3002 patients was randomized 2:1 to either the rapamycin/probucol-coated stent or the zotarolimus-eluting Resolute stent.
At one year, Mehilli reported here, rates of the primary end point--a composite of cardiac death, target-vessel-related MI, or target vessel revascularization (TVR)--were 13.1% in both groups. Rates of secondary end points were also comparable between stents.
ISAR-TEST 5: ISAR Dual-Drug Stent vs Zotarolimus-Eluting Stent Event Rates at One Year
| Event
|
ISAR
|
Resolute
|
RR (95% CI)
|
p
|
| Primary end point
|
13.1
|
13.1
|
1.03 (0.80–1.31)
|
0.83
|
| All-cause death
|
3.6
|
4.4
|
0.82 (0.56–1.20)
|
0.31
|
| Definite/probable stent thrombosis
|
1.1
|
1.2
|
0.94 (0.45–1.84)
|
0.91
|
| Cardiac death or MI
|
4.1
|
4.4
|
0.94 (0.65–1.36)
|
0.73
|
| Target lesion revascularization
|
10.3
|
10.0
|
0.99 (0.80–1.23)
|
0.94
|
Angiographic follow-up, conducted in 76% of patients at eight months, showed no differences in rates of binary restenosis (just over 13% for both groups) and in-stent late loss, which was 0.31 mm for the polymer-free stent and 0.30 mm for the Resolute.
In her concluding remarks, Mehilli emphasized that the trial was powered for clinical end points yet saw no differences between the two stents at 12 months. "Their performance was comparable with regard to hard clinical end points--stent thrombosis, death, or MI--as well as clinical and angiographic parameters of restenosis."
During a morning press conference, Dr Roxana Mehran (Columbia University, New York, NY) pointed out that the definite/probable stent-thrombosis rate seen for both stents in ISAR-TEST 5 was nearly double that seen in SPIRIT IV, presented earlier in the week, which was just 0.42% at two years. "That's a difficult one to beat," she said.
Of note, however, dual antiplatelet therapy was six months in ISAR-TEST 5, whereas three-quarters of patients in SPIRIT IV were still taking both clopidogrel and aspirin at two years.
The ultimate goal of a polymer-free stent would be to prove that is as effective as polymerized drug-eluting stents, but potentially requiring a shorter duration of dual antiplatelet therapy.
Promising, But Still Work to Do
According to ISAR-TEST 5 senior investigator Dr Adnan Kastrati (Deutsches Herzzentrum), speaking after the late-breaking clinical trial's presentation Saturday, the first step is to prove that the stent has comparable efficacy--something clearly shown here today.
"Then, if I have to choose between two equal stents, one with permanent polymer and one without, I think this [information] alone would be sufficient for our choice. But we need longer-term data," he said. "Once we have proven similar efficacy long term, we will launch further studies with less dual antiplatelet therapy."
The ISAR-TEST 5 results were well-received by a panel discussion following the presentation, in which it was pointed out that this study shows at least one-year noninferiority to a stent--the Resolute--that proved itself to be noninferior to the market-leading Xience/Promus stents. "These results are terrific," Dr Martin Leon (Columbia University, New York, NY) commented. "There has to be a future for this."
Kastrati, however, believes more studies are needed; although the stent-coating technology is CE Mark approved in Europe, it is not widely in use.
Others pointed out that it will be important to see whether there is any "late catch-up" restenosis, something many, including Dr Renu Virmani (CV Path, Washington, DC) earlier at this meeting, have predicted would come back to bite the polymer-free stents.
Mehilli disclosed having no conflicts of interest. Mehran receives research support from Bristol-Myers Squibb and Sanofi-Aventis and consults for Abbott, Accumetrics, AlphaMedica, AstraZeneca, Cardiva, Cordis, Gilead, Guerbet, the Medicines Company, Regado Biosciences, St Jude Medical, and Therox. Kastrati receives research support from Abbott and is a consultant for AstraZeneca and Biosensors and on the speakers' bureau for Cordis. Leon disclosed consulting for Angioscore and Neovasc and holding stock in Angioscore and Sadra Medical.
Heartwire from Medscape © 2010 Medscape, LLC
Cite this: ISAR-TEST 5: Dual-Drug Polymer-Free Stent Equals Zotarolimus-Eluting Resolute in All-Comers - Medscape - Sep 28, 2010.
