摘要
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/m2 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.
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/m2 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.
