COMPARE II and SORT OUT V Studies Published for Terumo's Nobori Stent

January 30, 2013—The COMPARE II and the SORT OUT V studies of the Nobori abluminal biodegradable polymer biolimus-eluting stent (Terumo Interventional Systems, Somerset, NJ) were published online ahead of print in The Lancet.

The COMPARE II investigators concluded that the Nobori stent is as safe and efficacious as the current standard of a thin-strut everolimus-eluting stent with a durable, biocompatible polymer. They advised that patients need follow-up for longer periods to show whether the biolimus-eluting stent reduces the risk of stent thrombosis after 1 year when compared with the everolimus-eluting stent.

However, the SORT OUT V investigators concluded that at 1-year follow-up, the biodegradable polymer biolimus-eluting Nobori stent did not improve clinical results compared with a first-generation sirolimus-eluting stent, and advised that long-term data would be needed before a recommendation could be made for the role of this biolimus-eluting stent in routine clinical practice.

COMPARE II was published in The Lancet by Pieter Cornelis Smits, MD, et al, who aimed to compare the safety and efficacy of the Nobori stent with a thin-strut everolimus-eluting stent coated with a durable biocompatible polymer (Xience V or Xience Prime, Abbott Vascular, Santa Clara, CA; or Promus, Boston Scientific Corporation, Natick, MA). COMPARE II was funded by Terumo Europe (Leuven, Belgium) and the Research Foundation of the Cardiology Department, Maasstad Hospital in Rotterdam, The Netherlands.

The COMPARE II investigators used limited exclusion criteria (age > 18 years, life expectancy > 5 years, reference vessel diameter 2–4 mm) to enroll patients eligible for percutaneous coronary intervention. Patients were randomly allocated (2:1) by computer-generated random numbers to receive either a Nobori stent or one of the everolimus-eluting stents. The primary endpoint was a composite of safety (cardiac death and non-fatal myocardial infarction) and efficacy (clinically indicated target-vessel revascularization) at 12 months, analyzed by intention to treat. Patients received dual-antiplatelet therapy for 12 months after discharge.

From January 12, 2009 to February 7, 2011, the COMPARE II investigators enrolled 2,707 patients (4,025 lesions). Of these patients, 1,795 were assigned to receive the biolimus-eluting stent (2,638 lesions) and 912 were assigned to receive an everolimus-eluting stent (1,387 lesions). There were 2,688 (99.3%) patients who completed 12-month follow-up.

The investigators found that significantly more patients in the Nobori biolimus-eluting stent group received a nonassigned stent than did those in the everolimus-eluting stent group (105 [5.9%] vs 19 [2.1%]; P < .0001). The primary endpoint occurred in 93 (5.2%) patients in the biolimus-eluting stent group and 44 (4.8%) patients in the everolimus-eluting stent group at 12 months (relative risk 1.07 [95% CI, 0.75–1.52]; P_{non-inferiority} < .0001). Analysis per protocol did not change the outcome of this trial (P_{non-inferiority} < .0001), reported the COMPARE II investigators in The Lancet.

As summarized in The Lancet, SORT OUT (Scandinavian Organization for Randomized Trials with Clinical Outcome) V was conducted by Høj Christiansen, PhD, et al to investigate the effects of a third-generation biodegradable polymer biolimus-eluting stent (Nobori) compared with a first-generation durable polymer-coated sirolimus-eluting stent in a population-based setting of unselected patients receiving percutaneous coronary intervention (Cypher Select Plus, Cordis Corporaton, Bridgewater, NJ). The SORT OUT V study was funded by Terumo and Cordis.

SORT OUT V was a randomized, multicenter, all-comer, noninferiority trial undertaken at three sites across western Denmark. Eligible patients were aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes and at least one coronary artery lesion (> 50% diameter stenosis).

The SORT OUT V investigators reported that from July 2009 to January 2011, they randomly assigned patients (1:1) using an independently managed, computer-generated allocation sequence to receive either a Nobori or Cypher Select Plus stent. The primary endpoint was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularization) at 9 months, analyzed by intention to treat (noninferiority margin of 0.02).

The investigators assigned 1,229 patients (1,532 lesions) to receive the Nobori biolimus-eluting stent and 1,239 (1,555 lesions) to receive the Cypher Select Plus sirolimus-eluting stent. One patient was lost to follow-up because of emigration.

As summarized in The Lancet, intention-to-treat analysis showed that 50 (4.1%) patients who were assigned the biolimus-eluting stent and 39 (3.1%) who were assigned the sirolimus-eluting stent met the primary endpoint (risk difference 0.9% [upper limit of one-sided 95% CI, 2.1%]; P_{non-inferiority} = .06). Significantly more patients in the biolimus-eluting stent group had definite stent thrombosis at 12 months than did those in the sirolimus-eluting stent group (9 [0.7%] vs 2 [0.2%], risk difference 0.6% [95% CI, 0.0–1.1]; P =.034). Per-protocol analysis showed that 45 (3.8%) of 1,193 patients who received a biolimus-eluting stent and 39 (3.2%) of 1,208 who received a sirolimus-eluting stent met the primary endpoint (risk difference 0.5% [upper limit of one-sided 95% CI, 1.8%]; P_{non-inferiority} = .03), reported the SORT OUT V investigators.