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. (Author correspondence: [email protected], [email protected])

Keywords:

• Acute stroke
• Circadian rhythms
• Stroke
• Thrombolysis
• tPA

ACKNOWLEDGMENTS

The authors are grateful to Professor Erik Cobo, from “Bioestadística para no estadísticos” Learning Program, UPC, Barcelona, for his statistical advice. Declaration of Interest: This project has been partially supported by grants from the Spanish Ministry of Science and Innovation (Fondo de Investigaciones Sanitarias, Instituto Salud Carlos III, RETICS-RD06/0026 and PI060788) and Xunta de Galicia (Consellería de Economía e Industria: 09CSA057918PR; Consellería de Sanidade: PS09/32).

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.