title: Combination therapy of intravenous glycoprotein IIB/IIIA inhibitors and tissue plasminogen activator for acute ischemic stroke.
abstract: OBJECTIVE
  Retrospective pooled analysis of data from published prospective studies and randomized phase 1 and 2 trials was done to assess efficacy and safety profile of intravenous combination therapy [glycoprotein IIb/IIIa inhibitors and IV tissue plasminogen activator (tPA)] in management of acute ischemic stroke.
  
  
  METHODS
  We searched Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, and EMBASE databases; two reviewers independently selected studies reporting safety endpoints and outcome measures in acute ischemic stroke patients treated with combination therapy. tPA arm of the National Institute of Neurological Disorders and Stroke (NINDS) tPA trial was included in tPA-only group. Weighted means and proportions were calculated for numeric and categorical variables respectively. Bivariate analysis using Fisher's exact test was done to compare baseline descriptors, safety endpoints, and outcome measures.
  
  
  RESULTS
  Combination therapy arm included 188 patients and IV tPA arm had 218 patients. Mean National Institutes of Health Stroke Scale (NIHSS) in two groups were 12.8 and 14.6, respectively. Mean time-to-treatment was 2.3 hours in combination therapy arm and 2.55 hours in tPA arm. Treatment with combination therapy was associated with significant reduction in rate of symptomatic intracranial hemorrhage (sICH) [odds ratio (OR) 0.26, 95% cumulative incidence (CI) 0.07 0.83, P value 0.01). Difference in better functional outcome at 90 days (OR 0.87, 95% CI 0.59-1.30, P value 0.54) and death at 90 days (OR 1.16, 95% CI 0.69-1.93, P value 0.60) were not significantly different in two groups.
  
  
  CONCLUSIONS
  Combination of low dose IV TPA with glycoprotein IIb/IIIa inhibitors is associated with reduction in sICH rates in patients with acute ischemic stroke as compared to standard dose of IV tPA.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, United State.
authors.forename: Divyanshu
authors.initials: D
authors.lastname: Dubey
authors.forename: Chirantan
authors.initials: C
authors.lastname: Banerjee
authors.forename: Anshudha
authors.initials: A
authors.lastname: Sawhney
authors.forename: Abhishek
authors.initials: A
authors.lastname: Sharma
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Alberts
mesh_terms: D000077284:Abciximab; D061605:Administration, Intravenous; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D008297:Male; D010455:Peptides / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010959:Tissue Plasminogen Activator; D000077542:Eptifibatide; D000077284:Abciximab