Mortality at 1 year with combination platelet glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction: GUSTO V randomized trial

JAMA. 2002 Nov 6;288(17):2130-5. doi: 10.1001/jama.288.17.2130.

Abstract

Context: Among patients with acute myocardial infarction, combination reperfusion therapy with a platelet glycoprotein IIb/IIIa receptor inhibitor (abciximab) and a half dose of a plasminogen activator (reteplase) did not significantly reduce mortality at 30 days compared with a full dose of reteplase. Rates of nonfatal ischemic complications were significantly diminished.

Objective: To determine if the beneficial effects of abciximab and reteplase (combination therapy) on early nonfatal complications would translate into a reduction in the risk of death by 1 year.

Design, setting, and patients: One-year follow-up of a randomized controlled trial (Global Use of Strategies To Open Coronary Arteries [GUSTO] V). Of 16 588 patients who had been treated in 820 community and referral hospitals in 20 countries between July 1999 and February 2001, mortality data were available for 16 453 (99.2%).

Intervention: Patients were randomly assigned to receive (intravenously) a standard dose of reteplase (two 10-U boluses, 30 minutes apart) or the combination of a standard dose of abciximab (0.25 mg/kg bolus, 0.125 microg/kg per minute infusion [maximum 10 micro g/min for 12 hours]) and a half dose of reteplase (two 5-U boluses, 30 minutes apart).

Main outcome measure: One-year all-cause mortality rates.

Results: All-cause mortality at 1 year occurred in 692 (8.38%) of 8260 patients in the reteplase group and 698 (8.38%) of the 8328 patients in the combination therapy group (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.90-1.11; P>.99). Reinfarction within the first 7 days occurred in 3.5% of patients in the reteplase group and 2.3% of patients in the combination therapy group, and was significantly associated with 1-year mortality (22.6% in patients with reinfarction vs 8.0% in patients without reinfarction; HR, 3.08; 95% CI, 2.53-3.75; P<.001). However, treatment assignment did not significantly influence time of mortality regardless of reinfarction status.

Conclusion: Combination therapy (abciximab and reteplase) did not reduce mortality over 1 year compared with fibrinolytic therapy with reteplase alone.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abciximab
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Immunoglobulin Fab Fragments / administration & dosage
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use*
  • Survival Analysis
  • Thrombolytic Therapy*
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Fibrinolytic Agents
  • Immunoglobulin Fab Fragments
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Recombinant Proteins
  • reteplase
  • Tissue Plasminogen Activator
  • Abciximab