title: Safety and outcomes following thrombolytic treatment in stroke patients who had received prior treatment with anticoagulants.
abstract: BACKGROUND
  Information is scare regarding the safety of intravenous thrombolysis in patients under anticoagulant treatment, given that this is an exclusion criterion in clinical trials. We analyzed the risk of hemorrhagic complications following thrombolysis in patients under treatment with low-molecular-weight heparins (LMWH) and oral anticoagulants (OA).
  
  
  METHODS
  In a multicentered prospective study of consecutive acute stroke patients treated with intravenous alteplase we recorded age, gender, baseline NIHSS score, treatment delay, risk factors, etiology and previous therapy. The neurological progress (National Institutes of Health Stroke Scale at 7 days) and functional evolution at 3 months (modified Rankin Scale score), mortality and symptomatic intracerebral hemorrhage (SICH) were compared between patients with LMWH or OA and those without prior anticoagulant therapy.
  
  
  RESULTS
  Of the 1,482 patients, 21 (1.4%) had received LMWH and 70 (4.7%) OA (international normalized ratio, INR, 0.9-2.0). Patients on OA were older, presented higher basal glucose levels, had been treated later and had a higher prevalence of hypertension, dyslipidemia, prior stroke, atrial fibrillation and cardioembolic pathologies. The severity of stroke on admission was similar in the different groups. The percentages of patients achieving independence (mRS 0-2) at 3 months were 33, 44 and 58 (LMWH, OA and no prior anticoagulant treatment, respectively; p = 0.02 for both comparisons of LMWH vs. no treatment and OA vs. no treatment); the mortality rates were 30, 25 and 12% (p = 0.010, p = 0.001, respectively) and the SICH were 14, 3 and 2% (p < 0.0001 for comparison of LMWH vs. no treatment). In the case of treatment with OA, the outcomes were independent of the INR value. Following adjustment for confounding variables, the prior use of OA was associated with higher mortality (OR: 2.15, 95% CI: 1.1-4.2; p = 0.026) but not with SICH transformation or lower probability of independence. The use of LMWH was associated with higher mortality (OR: 5.3, 95% CI: 1.8-15.5; p = 0.002), risk of SICH (OR: 8.4, 95% CI: 2.2-32.2; p = 0.002) and lower probability of achieving independence (OR: 0.3, 95% CI: 0.1-0.97; p = 0.043).
  
  
  CONCLUSIONS
  The use of intravenous thrombolysis appears to be safe in patients previously treated with OA with INR levels <2 since there is no increase in SICH. The prior use of LMWH appears to increase the risk of SICH, death and dependence and, as such, the decision for systemic treatment with thrombolytic agents needs to be taken with caution in these cases. Larger case series are necessary to confirm these findings.
authors.affiliation: Stroke Unit, Department of Neurology, University Hospital Ramón y Cajal, IRYCIS, Universidad de Alcalá de Henares, Madrid, Spain.
authors.forename: María-Consuelo
authors.initials: MC
authors.lastname: Matute
authors.forename: Jaime
authors.initials: J
authors.lastname: Masjuan
authors.forename: Jose-Antonio
authors.initials: JA
authors.lastname: Egido
authors.forename: Blanca
authors.initials: B
authors.lastname: Fuentes
authors.forename: Patricia
authors.initials: P
authors.lastname: Simal
authors.forename: Fernando
authors.initials: F
authors.lastname: Díaz-Otero
authors.forename: Gemma
authors.initials: G
authors.lastname: Reig
authors.forename: Exuperio
authors.initials: E
authors.lastname: Díez-Tejedor
authors.forename: Antonio
authors.initials: A
authors.lastname: Gil-Nuñez
authors.forename: Jose
authors.initials: J
authors.lastname: Vivancos
authors.forename: María
authors.initials: M
authors.lastname: Alonso de Leciñana
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D002543:Cerebral Hemorrhage / Q000453:epidemiology*; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D010959:Tissue Plasminogen Activator