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

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.

• Authors: G L Schaer, L J Spaccavento, K F Browne, K A Krueger, D Krichbaum, J M Phelan, W O Fletcher, C L Grines, S Edwards, M K Jolly, R J Gibbons
• Journal: Circulation (Circulation) Vol. 94 Issue 3 Pg. 298-307 (Aug 01 1996) ISSN: 0009-7322 [Print] United States
• PMID: 8759069 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinolytic Agents
• Placebos
• Poloxalene
• Technetium Tc 99m Sestamibi

Topics

• Adult
• Angioplasty, Balloon, Coronary
• Coronary Angiography
• Double-Blind Method
• Female
• Fibrinolytic Agents (therapeutic use)
• Humans
• Injections
• Male
• Middle Aged
• Myocardial Infarction (diagnostic imaging, therapy)
• Placebos
• Poloxalene (adverse effects, therapeutic use)
• Salvage Therapy
• Technetium Tc 99m Sestamibi
• Thrombolytic Therapy
• Treatment Outcome