BASKET-PROVE II, EVOLVE II Test Biodegradable-Polymer DES; No Late Stent Thrombosis Benefit

November 19, 2014

CHICAGO, IL – Two new studies testing first- and second-generation drug-eluting stents (DES) with a bioabsorbable polymer have shown that the two stents are noninferior compared with a durable-polymer DES.

In the BASKET-PROVE II study[1,2], an investigator-driven trial that tested the biodegradable polymer with a biolimus-eluting stent (Nobori, Terumo) against a second-generation everolimus-eluting stent (Xience Prime, Abbott Vascular) and a thin-strut bare-metal stent (ProKinetik, Biotronik), the Nobori stent was noninferior to the Xience Prime stent in the composite end point of cardiac death, MI, and target vessel revascularization (TVR). Compared with the bare-metal stent, the Nobori stent was superior in terms of efficacy, a difference that was driven by reductions in TVR rates.

In the per-protocol efficacy analysis, in which patients were mostly excluded because of dual-antiplatelet-therapy protocol violations, the biodegradable-polymer DES failed to meet the statistical definition of noninferiority compared with Xience Prime.

Regarding safety at 24 months, there was no significant differences in rates of death, MI, and TVR, and no difference in the rate of stent thrombosis between the three stents.

After presenting the results of BASKET-PROVE II at the American Heart Association (AHA) 2014 Scientific Sessions, Dr Christoph Kaiser (University Hospital, Basel, Switzerland) told heartwire there is absolutely no late advantage in using the biodegradable-polymer Nobori stent over the everolimus stent with a durable polymer. He said the additional cost of the Nobori stent is "not justified."

Dr Christoph Kaiser

Kaiser pointed out that BASKET-PROVE II was not powered to address differences in clinical outcomes, but he remains confident in the findings.

"The idea is that you get rid of the polymer and then you'd basically have a bare-metal stent, which we thought would be safer in later stages," he said. "We saw a little bit of a reduction in [definite/probable] late stent thrombosis—it was 0.4% with the Nobori stent and 0.7% with the Xience stent—but the overall events are so small. The difference is so small. To show a real difference, you'd need 20 000 patients to prove it. And because the difference is so small, it's probably not clinically meaningful."

The BASKET-PROVE II Study

BASKET-PROVE II included 2291 patients with acute or stable coronary disease requiring coronary stenting in large vessels (>3.0 mm in diameter). Patients received dual antiplatelet therapy with prasugrel (Effient, Lilly/Daiichi-Sankyo) for 12 months following DES implantation and for 4 weeks with the bare-metal stent. At 2 years, the primary end point—a composite of cardiac death, MI, and clinically indicated TVR at 2 years—occurred in 7.6% of patients treated with the Nobori stent, 6.8% treated with Xience Prime, and 12.7% treated with the bare-metal stent. Nobori was statistically noninferior to Xience but superior to the bare-metal stent.

For the combined safety end point of cardiac death, MI, or definite/probable stent thrombosis, the event rates in Nobori, Xience Prime, and the bare-metal stent arms were 3.7%, 3.8%, and 5.0%, respectively, which was not significant. Rates of definite and definite/probable stent thrombosis did not differ either.

Dr Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York), who was not affiliated with the trial, said BASKET-PROVE II is an exceptional study because it allows clinicians to view late-performance of three stent types. Importantly, the study included a broad population of patients undergoing coronary revascularization. She pointed to the very low event rates in the DES arms—less than 8% in both groups—and that both showed improved efficacy vs the bare-metal stent.

"There were no late safety events," said Mehran. "That's really important with the single-antiplatelet therapies. But please remember that these are underpowered studies with small patient numbers."

The Synergy Stent in Action

In the second study[3], EVOLVE II, presented by Dr Dean Kereiakes (Christ Hospital Heart and Vascular Center, Cincinnati, OH), the group compared a second-generation bioabsorbable-polymer everolimus-eluting stent (Synergy, Boston Scientific) and with a durable-polymer everolimus-eluting stent (Promus Element Plus, Boston Scientific) in 1684 patients.

At 1 year, the primary target lesion failure (TLF) end point, a composite of cardiac death, MI, or ischemia-driven revascularization, occurred in 6.5% of the Promus-treated patients and 6.7% of the Synergy patients. This difference was not significant, proving noninferiority between the two stents. There was no difference in revascularization or stent-thrombosis rates at 12 months. With Promus, there were two definite/three probable cases of stent thrombosis; with Synergy there were two definite/one probable cases of stent thrombosis.

Speaking with the media, Kereiakes said EVOLVE II "is a classic regulatory approval trial." The stent, he said, has the potential for benefit because it is designed to expedite healing within the vasculature.

One of the major differences between the Synergy stent and previous biodegradable-polymer DES is that it is thinner and takes just 3 to 4 months to absorb (compared with 9 months with the Nobori stent). Kereiakes said he will present these data on behalf of Boston Scientific to the US Food and Drug Administration in December, and barring any unforeseen circumstances, he expects the stent to be approved in 2015.

Kaiser reports payment from Eli Lilly and Daiichi-Sankyo for participating on a national advisory board; grants from Basel Cardiovascular Research Foundation, Stentys, Biotronik, Eli Lilly, Daiichi-Sankyo, Abbott Vascular, AstraZeneca; being on a speaker's bureau for Abbott Vascular; and consulting for Eli Lilly, Daiichi-Sankyo, AstraZeneca, and GE Healthcare. Disclosures for the coauthors are listed in the abstract. Kereiakes reports honoraria for consulting with Boston Scientific, Abbott Vascular, and Reva Medical, Harvard Clinical Research Institute, and Ablative Solutions. Disclosures for the coauthors are listed in the abstract.

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