Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction: Results of a randomized, double-blind, placebo-controlled trial

Gary L. Schaer, Leo J. Spaccavento, Kevin F. Browne, Karol A. Krueger, Daniel Krichbaum, John M. Phelan, William O. Fletcher, Cindy L. Grines, Suzanne Edwards, Michael K. Jolly, Raymond J Gibbons

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Abstract

Background: RheothRx (poloxamer 188) is a surfactant with hemorheological and antithrombotic properties that reduces myocardial reperfusion injury in animal models of myocardial infarction. The purpose of the present study was to evaluate the safety and efficacy of adjunctive therapy with poloxamer 188 in patients receiving thrombolytic therapy for acute myocardial infarction. Methods and Results: In this multicenter trial, we randomized 114 patients to a 48-hour infusion of poloxamer 188 or vehicle placebo beginning immediately after the initiation of thrombolytic therapy. Tomographic imaging with 99mTc sestamibi before reperfusion and again 5 to 7 days after the infarction was used to determine myocardium at risk for infarction, infarct size, and myocardial salvage. Radionuclide angiography at 5 to 7 days after infarction was used to measure left ventricular ejection fraction. The treated and control groups had comparable baseline characteristics, time to thrombolytic administration, and time to treatment with poloxamer 188 or placebo. Poloxamer 188 treated patients demonstrated a 38% reduction in median myocardial infarct size(25th and 75th percentile) compared with placebo (16% [7, 30] versus 26% [9, 43]; P=.031), greater median myocardial salvage (13% [7, 20] versus 4% [1, 15]; P=.033), and a 13% relative improvement in median ejection fraction (52% [43,60] versus 46% [35, 60]; P=.020). Poloxamer 188 treatment also resulted in a reduced incidence of reinfarction (1% versus 13%; P=.016). Poloxamer 188 was well tolerated without adverse hemodynamic effects or significant organ toxicity. Conclusions: Adjunctive therapy with poloxamer 188 resulted in substantial benefit in this randomized trial, including significantly smaller infarcts, greater myocardial salvage, better left ventricular function, and a lower incidence of in-hospital reinfarction. Although the mechanisms are unproven, poloxamer 188 treatment may accelerate thrombolysis, reduce reocclusion, and ameliorate reperfusion injury.

Original languageEnglish (US)
Pages (from-to)298-307
Number of pages10
JournalCirculation
Volume94
Issue number3
StatePublished - 1996

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Poloxamer
Thrombolytic Therapy
Myocardial Infarction
Placebos
Injections
Infarction
Radionuclide Angiography
Technetium Tc 99m Sestamibi
Myocardial Reperfusion Injury
Therapeutics
Incidence
Reperfusion Injury
Left Ventricular Function
Surface-Active Agents
Stroke Volume
Multicenter Studies
Reperfusion
Myocardium
Animal Models
Hemodynamics

Keywords

  • leukocytes
  • microcirculation
  • myocardial infarction
  • poloxamer 188
  • reperfusion
  • thrombolysis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction : Results of a randomized, double-blind, placebo-controlled trial. / Schaer, Gary L.; Spaccavento, Leo J.; Browne, Kevin F.; Krueger, Karol A.; Krichbaum, Daniel; Phelan, John M.; Fletcher, William O.; Grines, Cindy L.; Edwards, Suzanne; Jolly, Michael K.; Gibbons, Raymond J.

In: Circulation, Vol. 94, No. 3, 1996, p. 298-307.

Research output: Contribution to journalArticle

Schaer, GL, Spaccavento, LJ, Browne, KF, Krueger, KA, Krichbaum, D, Phelan, JM, Fletcher, WO, Grines, CL, Edwards, S, Jolly, MK & Gibbons, RJ 1996, 'Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction: Results of a randomized, double-blind, placebo-controlled trial', Circulation, vol. 94, no. 3, pp. 298-307.
Schaer, Gary L. ; Spaccavento, Leo J. ; Browne, Kevin F. ; Krueger, Karol A. ; Krichbaum, Daniel ; Phelan, John M. ; Fletcher, William O. ; Grines, Cindy L. ; Edwards, Suzanne ; Jolly, Michael K. ; Gibbons, Raymond J. / Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction : Results of a randomized, double-blind, placebo-controlled trial. In: Circulation. 1996 ; Vol. 94, No. 3. pp. 298-307.
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abstract = "Background: RheothRx (poloxamer 188) is a surfactant with hemorheological and antithrombotic properties that reduces myocardial reperfusion injury in animal models of myocardial infarction. The purpose of the present study was to evaluate the safety and efficacy of adjunctive therapy with poloxamer 188 in patients receiving thrombolytic therapy for acute myocardial infarction. Methods and Results: In this multicenter trial, we randomized 114 patients to a 48-hour infusion of poloxamer 188 or vehicle placebo beginning immediately after the initiation of thrombolytic therapy. Tomographic imaging with 99mTc sestamibi before reperfusion and again 5 to 7 days after the infarction was used to determine myocardium at risk for infarction, infarct size, and myocardial salvage. Radionuclide angiography at 5 to 7 days after infarction was used to measure left ventricular ejection fraction. The treated and control groups had comparable baseline characteristics, time to thrombolytic administration, and time to treatment with poloxamer 188 or placebo. Poloxamer 188 treated patients demonstrated a 38{\%} reduction in median myocardial infarct size(25th and 75th percentile) compared with placebo (16{\%} [7, 30] versus 26{\%} [9, 43]; P=.031), greater median myocardial salvage (13{\%} [7, 20] versus 4{\%} [1, 15]; P=.033), and a 13{\%} relative improvement in median ejection fraction (52{\%} [43,60] versus 46{\%} [35, 60]; P=.020). Poloxamer 188 treatment also resulted in a reduced incidence of reinfarction (1{\%} versus 13{\%}; P=.016). Poloxamer 188 was well tolerated without adverse hemodynamic effects or significant organ toxicity. Conclusions: Adjunctive therapy with poloxamer 188 resulted in substantial benefit in this randomized trial, including significantly smaller infarcts, greater myocardial salvage, better left ventricular function, and a lower incidence of in-hospital reinfarction. Although the mechanisms are unproven, poloxamer 188 treatment may accelerate thrombolysis, reduce reocclusion, and ameliorate reperfusion injury.",
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T1 - Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction

T2 - Results of a randomized, double-blind, placebo-controlled trial

AU - Schaer, Gary L.

AU - Spaccavento, Leo J.

AU - Browne, Kevin F.

AU - Krueger, Karol A.

AU - Krichbaum, Daniel

AU - Phelan, John M.

AU - Fletcher, William O.

AU - Grines, Cindy L.

AU - Edwards, Suzanne

AU - Jolly, Michael K.

AU - Gibbons, Raymond J

PY - 1996

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N2 - Background: RheothRx (poloxamer 188) is a surfactant with hemorheological and antithrombotic properties that reduces myocardial reperfusion injury in animal models of myocardial infarction. The purpose of the present study was to evaluate the safety and efficacy of adjunctive therapy with poloxamer 188 in patients receiving thrombolytic therapy for acute myocardial infarction. Methods and Results: In this multicenter trial, we randomized 114 patients to a 48-hour infusion of poloxamer 188 or vehicle placebo beginning immediately after the initiation of thrombolytic therapy. Tomographic imaging with 99mTc sestamibi before reperfusion and again 5 to 7 days after the infarction was used to determine myocardium at risk for infarction, infarct size, and myocardial salvage. Radionuclide angiography at 5 to 7 days after infarction was used to measure left ventricular ejection fraction. The treated and control groups had comparable baseline characteristics, time to thrombolytic administration, and time to treatment with poloxamer 188 or placebo. Poloxamer 188 treated patients demonstrated a 38% reduction in median myocardial infarct size(25th and 75th percentile) compared with placebo (16% [7, 30] versus 26% [9, 43]; P=.031), greater median myocardial salvage (13% [7, 20] versus 4% [1, 15]; P=.033), and a 13% relative improvement in median ejection fraction (52% [43,60] versus 46% [35, 60]; P=.020). Poloxamer 188 treatment also resulted in a reduced incidence of reinfarction (1% versus 13%; P=.016). Poloxamer 188 was well tolerated without adverse hemodynamic effects or significant organ toxicity. Conclusions: Adjunctive therapy with poloxamer 188 resulted in substantial benefit in this randomized trial, including significantly smaller infarcts, greater myocardial salvage, better left ventricular function, and a lower incidence of in-hospital reinfarction. Although the mechanisms are unproven, poloxamer 188 treatment may accelerate thrombolysis, reduce reocclusion, and ameliorate reperfusion injury.

AB - Background: RheothRx (poloxamer 188) is a surfactant with hemorheological and antithrombotic properties that reduces myocardial reperfusion injury in animal models of myocardial infarction. The purpose of the present study was to evaluate the safety and efficacy of adjunctive therapy with poloxamer 188 in patients receiving thrombolytic therapy for acute myocardial infarction. Methods and Results: In this multicenter trial, we randomized 114 patients to a 48-hour infusion of poloxamer 188 or vehicle placebo beginning immediately after the initiation of thrombolytic therapy. Tomographic imaging with 99mTc sestamibi before reperfusion and again 5 to 7 days after the infarction was used to determine myocardium at risk for infarction, infarct size, and myocardial salvage. Radionuclide angiography at 5 to 7 days after infarction was used to measure left ventricular ejection fraction. The treated and control groups had comparable baseline characteristics, time to thrombolytic administration, and time to treatment with poloxamer 188 or placebo. Poloxamer 188 treated patients demonstrated a 38% reduction in median myocardial infarct size(25th and 75th percentile) compared with placebo (16% [7, 30] versus 26% [9, 43]; P=.031), greater median myocardial salvage (13% [7, 20] versus 4% [1, 15]; P=.033), and a 13% relative improvement in median ejection fraction (52% [43,60] versus 46% [35, 60]; P=.020). Poloxamer 188 treatment also resulted in a reduced incidence of reinfarction (1% versus 13%; P=.016). Poloxamer 188 was well tolerated without adverse hemodynamic effects or significant organ toxicity. Conclusions: Adjunctive therapy with poloxamer 188 resulted in substantial benefit in this randomized trial, including significantly smaller infarcts, greater myocardial salvage, better left ventricular function, and a lower incidence of in-hospital reinfarction. Although the mechanisms are unproven, poloxamer 188 treatment may accelerate thrombolysis, reduce reocclusion, and ameliorate reperfusion injury.

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KW - microcirculation

KW - myocardial infarction

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KW - reperfusion

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