Prasugrel内服患者とクロピドグレル内服患者の虚血に
関する予後は同等である

TRILOGY ACS サブスタディ：抗血小板薬の比較の結果、血小板反応性には差が認められたが臨床上の予後は同等であった

TRILOGY ACS Substudy: Comparison of antiplatelet agents finds differences in platelet reactivity but similar clinical outcomes

ST上昇のない急性冠症候群（ACS）に対し血行再建術を施行されなかった患者において、prasugrelはクロピドグレルよりも、年齢、体重、および用量に関係なく血小板反応性を低下させた。しかし、血小板反応性と虚血に関するアウトカム発現には有意な相関を認めなかったとのLate Breaking Clinical Trialの結果が2012年American Heart Association学会で発表され、同時にJAMAオンライン版に掲載された。研究者らは、Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes（TRILOGY ACS）トライアルにおいて大規模な経時的血小板機能サブスタディを施行した。TRILOGY ACSの参加者9,326人中、27.5%がこのサブスタディに組み入れられ、1,286人はprasugrelを1,278人はクロピドグレルを投与された。患者はアスピリンとprasugrel（10または15mg/d）またはクロピドグレル（75mg/d）のいずれかを併用する群に無作為に割り付けられた。Prasugrelは年齢、体重および用量に関係なくクロピドグレルよりも血小板反応性を低下させた。30か月間の一次有効性エンドポイント（心血管死、心臓発作、または脳卒中）発現率に関し、prasugrelとクロピドグレルの間に有意差はなく、血小板反応性と虚血性アウトカム発現との間に有意な相関は認められなかった。

Among patients with acute coronary syndromes (ACS) without ST-segment elevation who were treated without revascularization, prasugrel was associated with lower platelet reactivity than clopidogrel, irrespective of age, weight, and dose. However, no significant difference was seen between platelet reactivity and occurrence of ischemic outcomes according to a study presented during a Late Breaking Clinical Trials session at the American Heart Association's Scientific Sessions 2012 and simultaneously published Online First in JAMA.

Paul A. Gurbel, M.D., of the Sinai Center for Thrombosis Research, Baltimore, and colleagues conducted a study to examine the differences in platelet reactivity and clinical outcomes among patients with acute coronary syndromes (ACS) being treated by the antiplatelet agents clopidogrel or prasugrel.

The investigators conducted a large serial platelet function substudy within the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial. It was a randomized, double-blind, active control, event-driven trial comparing prasugrel vs. clopidogrel therapy in patient with unstable angina or non-ST-segment elevation myocardial infarction who were management medically without planned revascularization.

The objectives of the study were to characterize differences in platelet reactivity between treatment groups over time, to delineate the relationship of platelet reactivity with ischemic end point occurrence, and to determine a threshold for high platelet reactivity that optimizes the ability to discriminate between patients with and without ischemic event occurrence.

From 2008 to 2011, patients with medically managed unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) were enrolled in the TRILOGY ACS trial comparing clopidogrel vs. prasugrel. Of 9,326 participants, 27.5 percent were included in a platelet function substudy, including 1,286 who received prasugrel and 1,278 who received clopidogrel. Patients were randomized to receive aspirin with either prasugrel (10 or 5 mg/d) or clopidogrel (75 mg/d); those 75 years or older or younger than 75 years but who weighed less than 132 lbs. received a 5-mg prasugrel maintenance dose.

The researchers found that "among patients with ACS without ST-segment elevation and initially managed without revascularization, prasugrel was associated with lower platelet reactivity than clopidogrel, irrespective of age, weight, and dose. Among those in the platelet substudy, no significant differences existed between prasugrel vs. clopidogrel in the occurrence of the primary efficacy end point [composite of cardiovascular death, heart attack, or stroke] through 30 months and no significant association existed between platelet reactivity and occurrence of ischemic outcomes."

The TRILOGY ACS study was funded by Eli Lilly and Daiichi Sankyo. Author disclosures are in the manuscript.