Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting 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.
BACKGROUND
Inhibition of the P2Y12 ADP-receptor with oral antiplatelet agents given to patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with improved outcomes, but this strategy is limited by the time required for maximal antiplatelet effect after administration. We examined the safety and tolerability of a novel, direct-acting, reversible, intravenous P2Y12 ADP-receptor antagonist, elinogrel, versus placebo when administered to STEMI patients before primary PCI.


METHODS
The ERASE MI trial was a pilot, phase IIA, randomized, double-blind, placebo-controlled, dose-escalation study designed to evaluate the safety and tolerability of escalating doses (10, 20, 40, and 60 mg) of elinogrel administered as a single intravenous bolus before the start of the diagnostic angiogram preceding primary PCI. Patients were randomly assigned in a 1:1 manner to either elinogrel or placebo within each dosing group; and all patients received a 600-mg clopidogrel loading dose, followed by a second 300-mg clopidogrel loading dose 4 hours after PCI. The major outcome, in-hospital bleeding, was assessed with the Thrombolysis in Myocardial Infarction and Global Strategies to Open Occluded Coronary Arteries bleeding scales. Pre-PCI corrected Thrombolysis in Myocardial Infarction frame count and ST-segment resolution were also evaluated.


RESULTS
Seventy patients were randomized in the dose-escalation study, but the dose-confirmation phase was not started because the trial was prematurely terminated for administrative reasons. The incidence of bleeding events was infrequent and appeared to be similar in patients treated with all doses of elinogrel versus placebo. No differences in serious adverse events, laboratory values, corrected Thrombolysis in Myocardial Infarction frame count, or ST resolution were demonstrated between elinogrel and placebo.


CONCLUSIONS
With the limitations of a small study sample size, this pilot study provided preliminary data on the feasibility and tolerability of escalating doses of a direct-acting, reversible, intravenous P2Y12 ADP-receptor antagonist, elinogrel, as an adjunctive therapy for primary PCI for STEMI.
Berger
Jeffrey S
JS
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA.
Roe
Matthew T
MT
Gibson
C Michael
CM
Kilaru
Rakhi
R
Green
Cynthia L
CL
Melton
Laura
L
Blankenship
James D
JD
Metzger
D Christopher
DC
Granger
Christopher B
CB
Gretler
Daniel D
DD
Grines
Cindy L
CL
Huber
Kurt
K
Zeymer
Uwe
U
Buszman
Pawel
P
Harrington
Robert A
RA
Armstrong
Paul W
PW
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12
C548576:P2RY12 protein, human; D004364:Pharmaceutical Preparations; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12