Effects of selective matrix metalloproteinase inhibitor (PG-116800) to prevent ventricular remodeling after myocardial infarction: results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) trial.
OBJECTIVE
We sought to determine whether matrix metalloproteinase (MMP) inhibitor, PG-116800, reduced left ventricular (LV) remodeling after myocardial infarction (MI).


BACKGROUND
PG-116800 is an oral MMP inhibitor with significant antiremodeling effects in animal models of MI and ischemic heart failure.


METHODS
In an international, randomized, double-blind, placebo-controlled study, 253 patients with first ST-segment elevation MI and ejection fraction between 15% and 40% were enrolled 48+/- 24 h after MI and treated with placebo or PG-116800 for 90 days. Major efficacy end points were changes in LV volumes as determined by serial echocardiography, and clinical and safety outcomes were also collected.


RESULTS
In total, 203 patients (80%) completed 90 days of treatment and had evaluable baseline and 90-day echocardiograms. The proportion of patients with anterior MI (78% vs. 81%) and primary percutaneous coronary intervention (90% vs. 91%) along with baseline LV ejection fraction (35.5% vs. 36.8%) did not differ between PG-116800-treated and placebo-treated patients. There was no difference in the change in LV end-diastolic volume index from days 0 to 90 with PG-116800 versus placebo (5.09 +/- 1.45 ml/m(2) vs. 5.48 +/- 1.41 ml/m2, p = 0.42). Changes in LV diastolic volume, LV systolic volume, LV ejection fraction, sphericity index, plus rates of death or reinfarction were not significantly improved with PG-116800. PG-116800 was well tolerated; however, there was increased incidence of arthralgia and joint stiffness without significant increase in overall musculoskeletal adverse events (21% vs. 15%, p = 0.33).


CONCLUSIONS
Matrix metalloproteinase inhibition with PG-116800 failed to reduce LV remodeling or improve clinical outcomes after MI.
Hudson
Michael P
MP
Henry Ford Heart and Vascular Institute, Detroit, Michigan 48202, USA.
Armstrong
Paul W
PW
Ruzyllo
Witold
W
Brum
Jose
J
Cusmano
Lisa
L
Krzeski
Piotr
P
Lyon
Robert
R
Quinones
Miguel
M
Theroux
Pierre
P
Sydlowski
Diana
D
Kim
Henry E
HE
Garcia
Mario J
MJ
Jaber
Wael A
WA
Weaver
W Douglas
WD
D015906:Angioplasty, Balloon, Coronary; D004311:Double-Blind Method; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000187:drug effects*
D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; C512048:PG-116800