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

Michael P. Hudson, Paul W. Armstrong, Witold Ruzyllo, Jose Brum, Lisa Cusmano, Piotr Krzeski, Robert Lyon, Miguel Quinones, Pierre Theroux, Diana Sydlowski, Henry E. Kim, Mario J. Garcia, Wael A. Jaber, W. Douglas Weaver

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)15-20
Number of pages6
JournalJournal of the American College of Cardiology
Volume48
Issue number1
DOIs
StatePublished - Jul 4 2006
Externally publishedYes

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Ventricular Remodeling
Matrix Metalloproteinase Inhibitors
Myocardial Infarction
Placebos
Stroke Volume
PG-116800
Arthralgia
Percutaneous Coronary Intervention
Matrix Metalloproteinases
Echocardiography
Animal Models
Heart Failure
Joints
Safety
Mortality
Incidence

ASJC Scopus subject areas

  • Nursing(all)

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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. / Hudson, Michael P.; Armstrong, Paul W.; Ruzyllo, Witold; Brum, Jose; Cusmano, Lisa; Krzeski, Piotr; Lyon, Robert; Quinones, Miguel; Theroux, Pierre; Sydlowski, Diana; Kim, Henry E.; Garcia, Mario J.; Jaber, Wael A.; Weaver, W. Douglas.

In: Journal of the American College of Cardiology, Vol. 48, No. 1, 04.07.2006, p. 15-20.

Research output: Contribution to journalArticle

Hudson, Michael P. ; Armstrong, Paul W. ; Ruzyllo, Witold ; Brum, Jose ; Cusmano, Lisa ; Krzeski, Piotr ; Lyon, Robert ; Quinones, Miguel ; Theroux, Pierre ; Sydlowski, Diana ; Kim, Henry E. ; Garcia, Mario J. ; Jaber, Wael A. ; Weaver, W. Douglas. / 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. In: Journal of the American College of Cardiology. 2006 ; Vol. 48, No. 1. pp. 15-20.
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abstract = "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.",
author = "Hudson, {Michael P.} and Armstrong, {Paul W.} and Witold Ruzyllo and Jose Brum and Lisa Cusmano and Piotr Krzeski and Robert Lyon and Miguel Quinones and Pierre Theroux and Diana Sydlowski and Kim, {Henry E.} and Garcia, {Mario J.} and Jaber, {Wael A.} and Weaver, {W. Douglas}",
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T1 - 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

AU - Hudson, Michael P.

AU - Armstrong, Paul W.

AU - Ruzyllo, Witold

AU - Brum, Jose

AU - Cusmano, Lisa

AU - Krzeski, Piotr

AU - Lyon, Robert

AU - Quinones, Miguel

AU - Theroux, Pierre

AU - Sydlowski, Diana

AU - Kim, Henry E.

AU - Garcia, Mario J.

AU - Jaber, Wael A.

AU - Weaver, W. Douglas

PY - 2006/7/4

Y1 - 2006/7/4

N2 - 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.

AB - 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.

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