title: Circadian rhythms in the efficacy of intravenous alteplase in patients with acute ischemic stroke and middle cerebral artery occlusion.
abstract: Circadian rhythm interactions of hemostatic factors can modify tissue plasminogen activator (tPA) effects. We assess the relationship of the time frame of intravenous tPA administration with the outcome of patients with acute ischemic stroke (AIS). We studied 135 consecutive patients with AIS and transcranial duplex documented middle cerebral artery (MCA) occlusion treated with intravenous tPA. Complete recanalization was defined as total improvement on thrombolysis in brain ischemia (TIBI) grades 2 h after tPA infusion. Clinical response was evaluated by the modified Rankin scale at 90 days. We determined plasminogen activator inhibitor-1 (PAI-1) levels in 33 patients with available plasma samples before treatment. Our results are follows: 92 (68.1%) patients were treated in the diurnal (9:00-21:00) and 43 (31.8%) in the nocturnal period (21:00-9:00). Complete recanalization was recorded in 52/135 (38.5%) patients. Both the rate of complete recanalization (45.6% vs. 23.2%; p = .01) and good clinical outcome (64.1% vs. 44.2%; p = .02) were significantly higher in the group of diurnal tPA administration compared with those treated in the nocturnal period. The adjusted odds ratio (OR) of diurnal tPA treatment for complete MCA recanalization was 2.37 (95% confidence interval [CI], 1.02-5.52; p = .045). Diurnal tPA infusion significantly improved the overall distribution of scores on the modified Rankin scale, as compared with nocturnal treatment (OR, 2.07; 95% CI, 1.16-4.64 by ordinal regression analysis). Low PAI-1 levels were associated with complete recanalization but did not significantly differ between the two time frames. In conclusion, diurnal administration of tPA is associated with complete MCA recanalization and better functional outcome at 90 days in patients with AIS.
authors.affiliation: Acute Stroke Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet s/n, Badalona, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Vilas
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gomis
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanco
authors.forename: Jordi
authors.initials: J
authors.lastname: Cortés
authors.forename: Mònica
authors.initials: M
authors.lastname: Millán
authors.forename: Natalia
authors.initials: N
authors.lastname: Pérez de la Ossa
authors.forename: Laura
authors.initials: L
authors.lastname: Dorado
authors.forename: Elena
authors.initials: E
authors.lastname: López-Cancio
authors.forename: Anna
authors.initials: A
authors.lastname: Suñol
authors.forename: Antoni
authors.initials: A
authors.lastname: Dávalos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy*; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000008:administration & dosage / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator