Combined anti-platelet therapy with aspirin and clopidogrel: risk factor for thrombolysis-related intracerebral hemorrhage in acute ischemic stroke?
OBJECTIVE
To date, pre-treatment with anti-platelet agents does not constitute a contraindication for thrombolysis in acute ischemic stroke. We tested the hypothesis that combined pre-treatment with aspirin and clopidogrel is a risk factor for thrombolysis-related symptomatic intracerebral hemorrhage (sICH).


METHODS
We retrospectively studied patients with acute ischemic stroke receiving standard i.v. thrombolytic therapy with rt-PA in our institution. Exclusion criteria were thrombolysis initiated later than 3 h from symptom onset or with non-tPA-agents, no follow-up imaging was performed and data on prior medication was missing. We recorded clinical baseline variables including known risk factors for ICH. Our outcome measure was the incidence of ICH defined as parenchymal hematoma type 2 with > or = 4 points deterioration on the National Institute of Health Stroke Scale score. We performed univariate analysis to determine risk factors for sICH.


RESULTS
We identified 102 patients receiving any thrombolysis of which 63 fulfilled the inclusion criteria. Mean age was 69 years, onset-to-treatment-time 138 min, 56% male, median NIHSS score was 10, and 3 patients received additional intra-arterial interventions. A total of 3 patients had received combined aspirin and clopidogrel treatment before thrombolysis. SICH occurred in 3/63 (4.7%) of patients. Out of these, 2 patients had received the combined anti-platelet treatment. In univariate analysis, only combined pre-treatment with aspirin and clopidogrel treatment were associated with the occurrence of sICH.


CONCLUSIONS
In our retrospective study, only pre-treatment with aspirin and clopidogrel was associated with thrombolysis-related intracerebral hemorrhage. This finding should be further validated in large prospective databases like the SITS-MOST registry.
Hermann
Andreas
A
Department of Neurology, University of Technology Dresden, Fetscherstrabetae 74, 01307, Dresden, Germany.
Dzialowski
Imanuel
I
Koch
Roland
R
Gahn
Georg
G
D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000139:chemically induced*; D000077144:Clopidogrel; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D019851:Thrombophilia / Q000150:complications / Q000188:drug therapy; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D000077144:Clopidogrel; D010959:Tissue Plasminogen Activator; D013988:Ticlopidine; D001241:Aspirin