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.