Elinogrel, an orally and intravenously available ADP-receptor antagonist

Summary

The antiplatelet therapy with aspirin and the ADP-receptor blocker clopidogrel is currently the standard medication after coronary intervention or after acute coronary syndrome to prevent recurrent ischemic events and reduce mortality. However, high interindividual response variability to antiplatelet treatment is described in up to 44% of treated patients. A poor response to clopidogrel is caused by multifactorial mechanisms. Individual risk assessment including platelet function testing (PFT) can help to identify high risk patients, although recent randomized trials to investigate effects of PFT-guided therapy have failed to detect an impact on prognostic outcome. Poor response to standard antiplatelet agents can be overcome by switching to alternate substances. Elinogrel is a novel competitive, reversible ADP-receptor antagonist available in oral and intravenous formulation. Additional treatment with elinogrel showed advantages over clopidogrel, including more rapid, less variable, and more complete inhibition of platelet function without significantly increased bleeding complications. This review gives an overview over the investigational drug elinogrel for use in a personalized antiplatelet approach.

Zusammenfassung

Die duale antithrombozytäre Therapie mit Aspirin und dem ADP-Rezeptor-Inhibitor Clopidogrel gehört zur Standardmedikation nach Koronarintervention oder akutem Koronarsyndrom, um das Auftreten kardiovaskulärer Ereignisse zu verringern. Jedoch ist eine hohe Variabilität in der Ansprechrate bei bis zu 44% aller behandelten Patienten beschrieben. Ein geringes Ansprechen auf Clopidogrel ist durch verschiedene Faktoren bedingt, weshalb eine individuelle Risikostratifizierung erfolgen sollte. Einer hohen residuellen Plättchenaktivität kann durch Anpassen der antiaggregatorischen Therapie begegnet werden.

Elinogrel, ein kompetitiver, reversibler ADPRezeptor-Antagonist wurde als begleitende Medikation zu einer plättchenhemmenden Therapie mit Clopidogrel eingesetzt und untersucht. Elinogrel ist sowohl zur intravenösen als auch zur oralen Gabe verfügbar. Der zusätzliche Einsatz von Elinogrel führte zu einer schnelleren maximalen und weniger variablen Plättchenhemmung als eine Clopidogrel- Monotherapie ohne signifikante Erhöhung von Blutungskomplikationen. Dieser Übersichtsartikel befasst sich mit dem Einsatz von Elinogrel in einer individuell angepassten antithrombozytären Therapie.

Keywords

Elinogrel - reversible P2Y₁₂ ADP receptor antagonist - antiplatelet therapy

Schlüsselwörter

Elinogrel - reversibler P2Y₁₂-ADP-Rezeptorantagonist - antithrombozytäre Therapie

• References

• 1 King 3^rd SB, Smith Jr SC, Hirshfeld Jr JW. et al. 2007 focused update of the ACC/ AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report if the American College of Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol 2008; 51: 172-209.
• 2 Geisler T, Grass D, Bigalke B. et al. The Residual Platelet Aggregation after Deployment of Intracoronary Stent (PREDICT) score. J Thromb Haemost 2008; 06: 54-61.
• 3 Price MJ, Berger PB, Teirstein PS. et al. GRAVITAS Investigators. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011; 305: 1097-1105.
• 4 Gretler DD, Conley PB, Andre P. et al. “First in human” experience with PRT060128, a new directacting, reversible, P2Y12 inhibitor for IV and oral use. J Am Coll Cardiol 2007; 09 (Suppl. 02) 326A.
• 5 Gurbel PA, Bliden KP, Antonino MJ. et al. The effect of elinogrel on high platelet reactivity during dual antiplatelet therapy and the relation to CYP2C19*2 genotype: first experience in patients. J Thromb Haemost 2010; 08: 43-53.
• 6 Berger JS, Roe MT, Gibson CM. et al. Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a directacting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rapid ReversAl of platelet thromboSis with intravenous Elinogrel before PCI to optimize reperfusion in acute Myocardial Infarction (ERASE MI) pilot trial. Am Heart J 2009; 158: 998-1004 e1.
• 7 Leonardi S, Rao SV, Harrington RA. et al. Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI). Am Heart J 2010; 160: 65-72.
• 8 Rao S. A randomized, double-blind, active controlled trial to evaluate intravenous and oral PRT060128 (elinogrel), a selective and reversible P2Y12 receptor inhibitor, vs. clopidogrel, as a novel antiplatelet therapy in patients undergoing non-urgent percutaneous coronary interventions (INNOVATE-PCI). ESC Congress, August 28 – September 1, 2010. in Stockholm, Sweden.:
• 9 Sabatine MS. Novel antiplatelet strategies in acute coronary syndromes. Cleve Clin J Med 2009; 76 (Suppl. 01) S8-S15.
• 10 Steinhubl SR, Oh JJ, Oestreich JH. et al. Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect. Thromb Res 2008; 121: 527-534.