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(Circulation. 1996;94:298-307.)
© 1996 American Heart Association, Inc.

Articles

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

the Section of Cardiology (G.L.S.), Rush Medical College, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill; University Medical Center of Southern Nevada (Las Vegas) (L.J.S.); Lakeland Regional Medical Center (K.F.B), Lakeland, Fla; Department of Cardiovascular Medicine (K.A.K., M.K.J.) and the Clinical Statistics Department (S.E.), Burroughs Wellcome Co, Research Triangle Park, NC; Cardiology Department (D.K.), Christ Hospital and Medical Center, Oak Lawn, Ill; Section of Cardiology (J.M.P.), Rush North Shore Medical Center, Skokie, Ill; Appleton Medical Center (W.O.F.), Appleton, Wis; William Beaumont Hospital (C.L.G.), Royal Oak, Mich; and the Section of Cardiovascular Diseases (R.J.G.), Mayo Clinic, Rochester, Minn.

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.

Key Words: poloxamer 188 • myocardial infarction • reperfusion • microcirculation • leukocytes • thrombolysis

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