Randomized trials show noninferiority of biodegradable polymer DES

Issue: March 2013

The results of two randomized trials — SORT OUT V and COMPARE II — have shown the biolimus-eluting biodegradable polymer stent to be noninferior when compared with two different durable polymer drug-eluting stents. However, a significantly higher proportion of patients in SORT OUT V who were treated with the biolimus-eluting stent had definite stent thrombosis at 12 months when compared with the sirolimus-eluting stent.

The results of both trials were published online recently by The Lancet.

COMPARE II

In the open-label, prospective, randomized controlled, noninferiority COMPARE II trial, researchers enrolled 2,707 patients (n=4,025 lesions) aged at least 18 years who had a life expectancy more than 5 years and a reference vessel diameter of 2 mm to 4 mm. Patients were randomly assigned 2:1 to receive either a biolimus-eluting biodegradable polymer stent (Nobori, Terumo; n=1,795) or a durable fluoropolymer-based everolimus-eluting stent (Xience V or Prime, Abbott Vascular; or Promus, Boston Scientific; n=912). The study’s primary endpoint was a composite of safety (cardiac death and nonfatal MI) and efficacy (clinically indicated target vessel revascularization) endpoints at 12 months.

According to researchers, the biolimus-eluting biodegradable polymer stent was noninferior compared with the everolimus-eluting stent regarding the primary endpoint (5.2% vs. 4.8%; P for noninferiority <.0001), which remained the same after investigators performed a per-protocol analysis. Additionally, the rate of stent thrombosis was similar between groups.

SORT OUT V

Conversely, in the randomized, multicenter, all-comer, noninferiority SORT OUT V trial, investigators compared the biolimus-eluting biodegradable polymer stent with the durable polymer-coated sirolimus-eluting stent (Cypher Select Plus, Cordis) and found outcomes that favored the durable polymer DES.

The trial involved 2,468 patients aged at least 18 years who had chronic stable CAD or ACS and at least one coronary artery lesion with >50% diameter stenosis. Patients were randomly assigned 1:1 to either receive the biolimus-eluting biodegradable polymer stent (n=1,229; 1,532 lesions) or the sirolimus-eluting stent (n=1,239; 1,555 lesions).

The rate of the primary endpoint, a composite of safety (cardiac death, MI or definite stent thrombosis) and efficacy (TVR) endpoints at 9 months, was higher in the biolimus-eluting stent arm (4.1% vs. 3.1%; P for noninferiority=.06); however, in per-protocol analysis, the biolimus-eluting stent was noninferior compared with the sirolimus-eluting stent (3.8% vs. 3.2%; P for noninferiority =.03). Furthermore, at 12 months, the rate of definite stent thrombosis was significantly higher in the biolimus-eluting stent arm (0.7% vs. 0.2%; P=.034).

Sorting out the data

In an accompanying editorial, Adnan Kastrati, MD, with the Technische Universität, Munich, and Franz-Josef Neumann, MD, with the Universitäts-Herzzentrum Freiburg-Bad Krozingen, wrote that the main statistical result of SORT OUT V primarily reflects the power provided by the large sample size rather than being a strong indication of a clinically relevant difference between the compared devices.

Adnan Kastrati

“Biodegradable polymer-based DES, including the Nobori stent, were developed to improve the long-term performance of devices. Experimental and clinical findings continue to nurture this hope,” Kastrati and Neumann wrote. “Long-term results from both SORT OUT V and COMPARE II will more clearly define the role of the biodegradable polymer-based Nobori stent in clinical practice.”

Julinda Mehilli, MD, with the Klinikum der Universitaet Munich, who wrote a separate editorial accompanying the COMPARE II trial, agreed with the need to conduct longer-term follow-up.

“[Investigators] should be encouraged to follow-up COMPARE II patients for up to 5 years, because the hypothesized advantage of biodegradable polymer DES is that noninferiority at 1 year should transform into long-term clinical superiority over durable polymer DES,” she wrote. “Only then can we be certain that a stent with a disappearing polymer provides lasting clinical benefit for patients treated in routine practice.”

For more information:

Christiansen EH. Lancet. 2013;doi:10.1016/S0140-6736(12)61962-X.

Kastrati A. Lancet. 2013;doi:10.1016/S0140-6736(13)60055-0.

Mehilli J. Lancet. 2013;doi:10.1016/S0140-6736(12)62193-X.

Smits PC. Lancet. 2013;doi:10.1016/S0140-6736(12)61852-2.

Disclosure: Christiansen has received honoraria and travel grants from Cordis and Terumo; Kastrati has received lecture fees from Abbott, Biotronik, Cordis and Medtronic, and has submitted patent applications regarding DES technology; Mehilli has received lecture fees from Abbott Vascular, Eli Lilly/Daiichi Sankyo, Terumo, The Medicines Company and Translumina; Neumann reports no relevant financial disclosures; Smits is a consultant for Blue Medical and has received lecture and travel fees from Abbott Vascular.