Elinogrelは有望な血小板阻害薬である

INNOVATE PCI：Elinogrelは急性および慢性疾患の治療においてクロピドグレルよりも優れた抗血小板作用を発揮する
INNOVATE PCI: Elinogrel provides more potent antiplatelet effect than clopidogrel in acute and chronic phases of therapy
急性および慢性疾患の治療において経口および静脈内elinogrelはクロピドグレルよりも迅速な抗血小板作用を有するとのトライアルの結果が2010年European Society of Cardiology学会のホットラインセッションで発表された。このINNOVATE PCIスタディは、非緊急PCIを施行される患者652人においてP2Y12阻害薬elinogrel（このIV型が迅速な可逆性の血小板阻害を有する）とクロピドグレルを比較した、無作為化用量設定トライアルである。患者は最初にPCI前にクロピドグレルを1日300または600mgの後に75mgを内服、またはelinogrel 80mgをボーラスで静脈内投与しその後50、100または150mgの経口elinogrelを1日2回内服する群に無作為に割り付けられた。データ＆安全性モニタリング委員会は50mg経口投与群への組み入れを中止し静脈内投与の用量を120mgに増量することを推奨した；590人の患者は60日間追跡され、328人は120日間追跡された。スタディは有効性を評価する検出力に欠けていたが、elinogrelの静脈内投与および経口投与はクロピドグレルよりも有効である可能性があるようであり、阻害力は高用量で高いようであった。これらの結果は、さらに大規模なトライアルで臨床エンドポイントを評価しelinogrelをさらに研究するための基礎となりうる。
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Investigators showed that treatment with oral and intravenous elinogrel had more rapid antiplatelet effects than clopidogrel in the acute and chronic phases of therapy. Although still in early days, the hope is that reversible platelet inhibition may mitigate some of the bleeding risks and improve clinical outcomes. The study was presented in a Hotline session at ESC 2010.

Phase 2 trial results for elinogrel, a novel antiplatelet agent available in both intravenous and oral formulations, were presented in a Hotline session at ESC 2010.

The study, INNOVATE PCI, was a randomized dose-ranging trial that compared elinogrel, a P2Y12 inhibitor, which in its IV form, provides rapid, reversible platelet inhibition, with clopidogrel in 652 patients undergoing non-urgent PCI. Current P2Y12 antagonists are taken orally and require several hours to reach maximal platelet inhibition. The most widely used P2Y12 inhibitor is clopidogrel, which has significant variability in response (and a lack of response in some patients).

According to the INNOVATE PCI trial, elinogrel provides a more potent antiplatelet effect in both the IV and oral forms; however, this immediate platelet inhibition has yet to be translated into a reduction in hard clinical endpoints.

Patients were initially assigned pre-PCI to clopidogrel 300 or 600 mg followed by 75 mg/day, or to elinogrel 80 mg IV bolus followed by 50, 100, or 150 mg oral elinogrel twice daily. The Data & Safety Monitoring Committee recommended discontinuation of enrolment into the 50 mg oral dose arm and increasing elinogrel IV dose to 120 mg; 590 patients were followed for 60 days, and 328 for 120 days.

While the study was not powered to determine efficacy, principal investigator Dr. Sunil Rao from the Duke Clinical Research Institute, Durham, USA, said the results now provide a basis for further exploration of elinogrel in larger trials examining clinical endpoints. Rao explained that a pharmacodynamic sub-study provided two key findings as the basis for this further research: elinogrel appeared to be more potent than clopidogrel in platelet inhibition and inhibition appeared greater at higher doses.

"While clopidogrel is a well established and effective therapy," said Rao, "it doesn't work for all patients, so it is important that we explore alternatives to improve efficacy help prevent serious complications."

Clopidogrel is recommended for treatment of patients with acute coronary syndrome and/or PCI. However, the delayed onset of effect and varied response are associated with a raised risk of stent thrombosis. The molecular target of clopidogrel and newer antiplatelet agents is the P2Y12 receptor, which is the main platelet receptor responsible platelet aggregation.