Matrix metalloproteinase inhibition with PG-116800 did not significantly reduce the change in left ventricular end-diastolic volume index compared to placebo (5.09 vs 5.48 ml/m2; P=0.42).
RCT (n=253)
double-blind
randomized
Yes
Does the selective matrix metalloproteinase inhibitor PG-116800 reduce left ventricular remodeling in patients with first ST-segment elevation MI and LVEF 15-40%?
The selective matrix metalloproteinase inhibitor PG-116800 did not reduce left ventricular remodeling or improve clinical outcomes when administered for 90 days after a first STEMI.
Absolute Event Rate: 5.09% vs 5.48%
p-value: p=0.42
OBJECTIVES: 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 et al. (Thu,) conducted a rct in ST-segment elevation myocardial infarction with reduced ejection fraction (n=253). PG-116800 vs. Placebo was evaluated on Change in left ventricular end-diastolic volume index from days 0 to 90 (p=0.42). Matrix metalloproteinase inhibition with PG-116800 did not significantly reduce the change in left ventricular end-diastolic volume index compared to placebo (5.09 vs 5.48 ml/m2; P=0.42).