スタディの結果、薬剤溶出ステントの非劣性が確認された

RESET：PCI患者におけるエベロリムス溶出ステントのシロリムス溶出ステントに対する非劣性が認められた
RESET: Everolimus-eluting stents found to be non-inferior to sirolimus-eluting stents in PCI patients
第二世代の薬物溶出ステント（エベロリムス溶出ステント[EES]）は第一世代薬物（パクリタキセル）溶出ステントよりも無作為化コントロールトライアルにおいて常に一貫して優れた臨床成績を示してきた。しかし、EESを他の第一世代薬剤溶出ステント（シロリムス溶出ステント[SES]）と比較した早期のスタディではEESの非劣性のみが示された；標的病変での血行再建におけるSESと比較したEESの優越性は適切に調査されていない。これについて現在、EESとSESを日本の日常臨床で比較した、前向き無作為化多施設オープンラベルトライアル（Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial：RESET）により検討されている。薬剤溶出ステントによる経皮的冠動脈形成術を予定されている患者は、除外基準を用いずに組み入れた。一次有効性エンドポイントは標的病変の血行再建であった。RESETでは3,197人の患者を2つのステントのいずれかを埋め込まれる群に無作為に割り付けた。8ヵ月後のセグメント内後期内腔減少（in-segment late lumen loss） および造影上再狭窄率を評価した冠動脈造影サブスタディには571人の患者を組み入れた。このスタディ対象者には高齢、糖尿病およびPCI歴を有する者が高率であった。2011年European Society of Cardiology学会で発表された結果では、1年後の標的病変血行再建術および8～12ヵ月後の冠動脈造影上のセグメント内後期内腔減少においてSESに対しEESが非劣性であることが示された。
Full Text

The second generation drug-eluting stent, everolimus-eluting stent (EES), has consistently demonstrated superior clinical outcomes in randomized controlled trials over the first generation drug-eluting stent, paclitaxel-eluting stent. However, other earlier studies comparing EES with another first generation drug-eluting stent, sirolimus-eluting stent (SES), have only demonstrated the non-inferiority of EES; the superiority of EES relative to SES in terms of target-lesion revascularization has not yet been investigated in adequately powered randomized controlled trials.

This has now been addressed in the Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial (RESET), a prospective randomized multicenter open label trial comparing EES with SES in daily clinical practice in Japan. The trial was performed in patients scheduled for percutaneous coronary intervention with drug-eluting stents, who were enrolled without any exclusion criteria. The primary efficacy endpoint was defined as any target-lesion revascularization. The trial was a sequential non-inferiority and superiority study, which was powered for non-inferiority on the primary efficacy endpoint at one year after the index procedure.

Between February and July 2010, a total of 3206 patients were enrolled in the trial among 100 participating centers. Excluding nine patients who withdrew consent, 3197 patients were randomly assigned to receive either of the two investigation stents.

An angiographic sub-study evaluating in-segment late lumen loss and angiographic restenosis rate at eight months included 571 patients. The study population included large proportions of patients with advanced age, diabetes and prior PCI. The two groups of patients were well balanced in terms of baseline clinical, angiographic and procedural characteristics.

Results of this large randomized trial comparing showed EES to be non-inferior to SES in terms of target-lesion revascularization rate at one year and angiographic in-segment late loss at 8-12 months.

"One-year clinical outcome after both EES and SES use was excellent," said investigator Dr. Takeshi Kimura from Kyoto University Hospital, Kyoto, Japan, "with low rate of target-lesion revascularization and very low rate of stent thrombosis."

However, Dr. Kimura cautioned about several limitations to the study. First, he said, although SES was not widely used at the time of the trial, it was the most widely used and most extensively studied first generation DES. Clinical outcome after SES implantation should be regarded as the benchmark for the current and future generation drug-eluting stents.

Second, despite the all-comers trial design, the study population actually enrolled seemed to represent relatively low-risk patients, resulting in event rates lower than anticipated. Future stent trials, he suggested, might focus more on complex patients, in whom coronary artery bypass grafting could be a reasonable alternative.

Dr. Kimura also added that longer-term follow-up is important to address whether EES might affect the late adverse events beyond one year such as late restenosis and very late stent thrombosis.