title: Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset.
abstract: OBJECTIVE
  Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke.
  
  
  METHODS
  We assessed the safety of thrombolysis under APs in 11,865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale >or=4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale >or=4 plus any ICH]), functional outcome at 3 months and mortality.
  
  
  RESULTS
  A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogrel, 175 (1.5%) ASA and dipyridamole, 151 (1.3%) ASA and clopidogrel, and 197 (1.7%) others. Patients receiving APs were 5 years older and had more risk factors than AP naïve patients. Incidences of SICH per SITS-MOST (ECASS II respectively) were as follows: 1.1% (4.1%) AP naïve, 2.5% (6.2%) any AP, 2.5% (5.9%) ASA, 1.7% (4.2%) clopidogrel, 2.3% (5.9%) ASA and dipyridamole, and 4.1% (13.4%) ASA and clopidogrel. In multivariable analyses, the combination of ASA and clopidogrel was associated with increased risk for SICH per ECASS II (odds ratio, 2.11; 95% CI, 1.29 to 3.45; P=0.003). However, we found no significant increase in the risk for mortality or poor functional outcome, irrespective of the AP subgroup or SICH definition.
  
  
  CONCLUSIONS
  The absolute excess of SICH of 1.4% (2.1%) in the pooled AP group is small compared with the benefit of thrombolysis seen in randomized trials. Although caution is warranted in patients receiving the combination of ASA and clopidogrel, AP treatment should not be considered a contraindication to thrombolysis.
authors.affiliation: Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Diedler
authors.forename: Niaz
authors.initials: N
authors.lastname: Ahmed
authors.forename: Marek
authors.initials: M
authors.lastname: Sykora
authors.forename: Maarten
authors.initials: M
authors.lastname: Uyttenboogaart
authors.forename: Karsten
authors.initials: K
authors.lastname: Overgaard
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Luijckx
authors.forename: Lauri
authors.initials: L
authors.lastname: Soinne
authors.forename: Gary A
authors.initials: GA
authors.lastname: Ford
authors.forename: Kennedy R
authors.initials: KR
authors.lastname: Lees
authors.forename: Nils
authors.initials: N
authors.lastname: Wahlgren
authors.forename: Peter
authors.initials: P
authors.lastname: Ringleb
mesh_terms: D000208:Acute Disease / Q000453:epidemiology / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D000077144:Clopidogrel; D000075202:Contraindications; D004176:Dipyridamole / Q000008:administration & dosage / Q000009:adverse effects; D004344:Drug Incompatibility; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous / Q000009:adverse effects / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D018570:Risk Assessment; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D000077144:Clopidogrel; D010959:Tissue Plasminogen Activator; D013988:Ticlopidine; D001241:Aspirin