• Coronary Artery Disease
• Interventional Techniques & Devices
• Cardiology Clinical Trials
• Thrombotic Disorders

Elinogrel, an investigational P2Y₁₂ inhibitor, showed potent antiplatelet activity in the phase II Randomized, Double-Blind, Active Controlled Trial to Evaluate Intravenous and Oral PRT060128 (elinogrel), a Selective and Reversible P2Y₁₂ Receptor 0Inhibitor, versus Clopidogrel, as a Novel Antiplatelet Therapy in Patients Undergoing Nonurgent Percutaneous Coronary Interventions (INNOVATE PCI) trial. Compared with clopidogrel, elinogrel provided greater and more rapid platelet inhibition without increasing bleeding risk in patients who were undergoing elective percutaneous coronary intervention (PCI).

Stronger platelet inhibition has the potential to improve ischemic outcomes but often at the cost of increased major bleeding. Reversible platelet inhibition may lessen the risk of bleeding complications. Elinogrel is the only antiplatelet agent to competitively and reversibly bind the P2Y₁₂ receptor. The agent can be administered both intravenously and orally, enabling acute and long-term use.

In the INNOVATE PCI trial, 652 patients who were scheduled to undergo nonurgent PCI were randomly assigned to treatment with clopidogrel with an IV loading dose of 300 to 600 mg followed by 75 mg/day, or elinogrel with an IV loading dose of 80 mg followed by oral elinogrel 50 mg, 100 mg, or 150 mg twice daily. After study enrollment began, the protocol was adjusted to eliminate the elinogrel 50-mg dose and increase the elinogrel IV loading dose to 120 mg.

INNOVATE PCI was not powered for any specific endpoint but instead explored a range of efficacy, safety, and tolerability outcomes. Sunil Rao, MD, Duke University Medical Center, Durham, North Carolina, USA, reported findings from the INNOVATE PCI study.

Elinogrel provided a more rapid reduction in platelet aggregation compared with clopidogrel, with greater platelet inhibition at 30 minutes, 2 hours, and 20 hours after administration (p<0.025 for all comparisons). At 30 days, platelet inhibition remained greater with the elinogrel 100-mg and 150-mg oral doses compared with clopidogrel 75 mg.

There were no significant differences in ischemic event rates between the elinogrel and clopidogrel groups at 24 hours or 120 days, suggesting similar acute and chronic efficacy. Biological activity was also comparable, with similar degrees of troponin elevation in both treatment groups. Elinogrel did not increase the risk of TIMI major or minor bleeding compared with clopidogrel at either time point.

Dyspnea was more common with elinogrel 100 mg (15.4%) and elinogrel 150 mg (12.1%) compared with clopidogrel (4.3%), but most cases were mild and transient. Patients in the elinogrel 100-mg and 150-mg groups were more likely to develop elevated liver transaminases (2% and 3.4%, respectively) compared with clopidogrel (0.5%).

Following the promising results of INNOVATE PCI, a phase III trial of elinogrel in patients with chronic coronary heart disease will launch in early 2011. The trial will enroll approximately 24,000 patients with a history of myocardial infarction (MI). Patients will be randomized to low-dose or high-dose elinogrel or placebo. The primary efficacy endpoint will be cardiovascular death, MI, or stroke.

• © 2010 MD Conference Express