Preliminary experience with intravenous P2Y12 platelet receptor inhibition as an adjunct to reduced-dose alteplase during acute myocardial infarction: results of the Safety, Tolerability and Effect on Patency in Acute Myocardial Infarction (STEP-AMI) angiographic trial.
BACKGROUND
Fibrinolytic therapy for acute myocardial infarction (AMI) results in normal flow in only about half of patients. Adjunctive treatment with potent antiplatelet and antithrombin agents increases arterial patency but is associated with excessive bleeding. Cangrelor (formerly AR-C69931MX) is a rapidly acting, specific antagonist of platelet aggregation via binding to the adenosine diphosphate P2Y12 receptor subtype. The aim of this study was to assess the safety and coronary artery patency of cangrelor as an adjunct to alteplase (tissue plasminogen activator [t-PA]).


METHODS
Patients with AMI received aspirin, heparin, and an intravenous infusion of either cangrelor alone, full-dose t-PA alone, or 1 of 3 doses of cangrelor along with half-dose t-PA. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 60 minutes. Secondary end points included TIMI frame count, TIMI myocardial perfusion grade, extent of ST-segment resolution, composite clinical events, and bleeding.


RESULTS
Ninety-two of planned 180 patients were enrolled. The combination of cangrelor and half-dose t-PA resulted in similar 60-minute patency as full-dose t-PA alone (55% vs 50%, P = not significant) and greater patency than with cangrelor alone (55% vs 18%, P < .05). The percentage of patients achieving >70% ST-segment resolution at 60 minutes tended to be greater with combination therapy than with either cangrelor or t-PA alone (28% vs 13%, P = .13 and 28% vs 14%, P = .30, respectively). Bleeding and adverse clinical events were comparable among the groups.


CONCLUSIONS
This first experience with the intravenous P2Y12 receptor inhibitor, cangrelor, suggests the potential of this compound as an adjunct to fibrinolysis during treatment of AMI.
Greenbaum
Adam B
AB
Henry Ford Heart and Vascular Institute, Detroit, MI, USA. agreenb1@hfhs.org
Ohman
E Magnus
EM
Gibson
C Michael
CM
Borzak
Steven
S
Stebbins
Amanda L
AL
Lu
Mei
M
Le May
Michel R
MR
Stankowski
Jill E
JE
Emanuelsson
Hakan
H
Weaver
W Douglas
WD
D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D009203:Myocardial Infarction / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014654:Vascular Patency / Q000187:drug effects*
D005343:Fibrinolytic Agents; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000249:Adenosine Monophosphate; C117446:cangrelor; D010959:Tissue Plasminogen Activator