A randomized, double-blinded, placebo-controlled, dose-ranging study measuring the effect of an adenosine agonist on infarct size reduction in patients undergoing primary percutaneous transluminal coronary angioplasty: the ADMIRE (AmP579 Delivery for Myocardial Infarction REduction) study.
BACKGROUND
Evidence suggests that myocardial ischemic preconditioning and reperfusion injury may be mediated by adenosine A1 and A2 receptors. AMP579 is a mixed adenosine agonist with both A1 and A2 effects. In animal models of acute myocardial infarction (MI), AMP579 reduced infarct size at serum levels of 15 to 24 ng/mL.


METHODS
The AMP579 Delivery for Myocardial Infarction REduction study evaluated AMP579 in a double-blind, multicenter, placebo-controlled trial of 311 patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) after acute ST-segment elevation MI. Patients were randomly assigned to placebo or to 3 different doses of AMP579 continuously infused over 6 hours. The primary end point was final MI size measured by technetium Tc-99m sestamibi scanning at 120 to 216 hours after PTCA. Secondary end points included myocardial salvage and salvage index at the same time interval (in a subset of patients who underwent baseline technetium Tc-99m sestamibi scan), left ventricular ejection fraction and heart failure at 4 to 6 weeks, duration of hospitalization, and cardiac events at 4 weeks and 6 months.


RESULTS
Final infarct size did not differ among the placebo group and the active treatment groups for either anterior MI or nonanterior MI. In patients with anterior MI, median myocardial salvage was increasingly higher in the groups receiving ascending dosages of AMP579 plus PTCA. Serum levels approaching levels shown to reduce infarct size in animal models were achieved only in the 60-mcg/kg treatment group.


CONCLUSIONS
AMP579 was safe at the doses tested, but it did not reduce infarct size. There was a trend toward greater myocardial salvage in treated patients with anterior MI.
Kopecky
Stephen L
SL
Mayo Alliance for Clinical Trials, Mayo Clinic and Mayo Foundation, Rochester, MN 55902, USA. kopecky.stephen@mayo.edu
Aviles
Ronnier J
RJ
Bell
Malcolm R
MR
Lobl
Joseph K
JK
Tipping
Diane
D
Frommell
Gregg
G
Ramsey
Karen
K
Holland
Anne E
AE
Midei
Mark
M
Jain
Abnash
A
Kellett
Mirle
M
Gibbons
Raymond J
RJ
D000241:Adenosine / Q000819:agonists*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015906:Angioplasty, Balloon, Coronary; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D017256:Technetium Tc 99m Sestamibi
C113971:4-(7-((2-3-chloro-2-thienyl)-1-methyl-propylamino)-3H-imidazo(4,5-b)pyridyl-3-yl)cyclopentane carboxamide; D007093:Imidazoles; D011725:Pyridines; D017256:Technetium Tc 99m Sestamibi; D000241:Adenosine