Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset.
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.
Diedler
Jennifer
J
Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Ahmed
Niaz
N
Sykora
Marek
M
Uyttenboogaart
Maarten
M
Overgaard
Karsten
K
Luijckx
Gert-Jan
GJ
Soinne
Lauri
L
Ford
Gary A
GA
Lees
Kennedy R
KR
Wahlgren
Nils
N
Ringleb
Peter
P
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
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D000077144:Clopidogrel; D010959:Tissue Plasminogen Activator; D013988:Ticlopidine; D001241:Aspirin