Hyperfibrinogenemia and functional outcome from acute ischemic stroke

Abstract

Background and purpose: Epidemiological studies have found strong correlations between elevated plasma fibrinogen levels and both ischemic stroke incidence and stroke mortality. Little is known about the influence of fibrinogen levels on functional stroke outcome.

Methods: Placebo data from the Stroke Treatment with Ancrod Trial (STAT) and European Stroke Treatment with Ancrod Trial (ESTAT) were analyzed. Fibrinogen levels were determined within 3 hours (STAT) or 6 hours (ESTAT) of stroke onset and at preset intervals throughout 5 days of intravenous infusions. Barthel Index scores at 90 days quantified functional outcomes. The association between initial fibrinogen levels and functional outcomes was evaluated using a multiple logistic regression analysis.

Results: Fibrinogen levels increased gradually over the first 24 hours from a pretreatment median value of 340 mg/dL to a 24-hour median value of 376 mg/dL. In a univariate analysis, the proportion of patients with good functional outcome decreased with increasing quartiles of initial fibrinogen levels in both STAT (36.0% to 26.2%) and ESTAT (53.8% to 24.8%). In a multifactorial analysis, the same trend was observed. Patients with initial fibrinogen levels <450 mg/dL had better outcomes in both studies; the difference (42.0% versus 21.6%) was significant in ESTAT (P=0.0006), even when corrected for age and initial stroke severity.

Conclusions: The independent association of higher initial fibrinogen levels with poor outcome needs to be verified using a larger acute stroke dataset. Even in the present small populations, the apparent association of these 2 variables suggests that treatments designed to reduce fibrinogen levels could potentially be important in treating acute ischemic stroke.

Figure 1

Profile of mean plasma fibrinogen levels after stroke onset in placebo-treated patients enrolled in STAT. Numbers of observations for each time point fall from 250 at 0 hours to 210 at 120 hours; all standard errors of the mean are <10 mg/dL.

Figure 2

Good functional outcome (proportion with 95% CIs) at 90 days after ischemic stroke in placebo-treated patients enrolled in STAT, stratified to determine initial study drug infusion rates by fibrinogen levels measured within 3 hours of stroke onset (covariate-adjusted for age and pretreatment stroke severity).

Figure 3

Good functional outcome at 90 days after ischemic stroke in placebo-treated patients enrolled in STAT, stratified by quartiles of fibrinogen levels measured within 3 hours of stroke onset (covariate-adjusted for age and pretreatment stroke severity).

Figure 4

Good functional outcome (proportion with 95% CIs) at 90 days after ischemic stroke in placebo-treated patients enrolled in ESTAT, stratified to determine initial study drug infusion rates by fibrinogen levels measured within 6 hours of stroke onset (covariate-adjusted for age and pretreatment stroke severity).

Figure 5

Good functional outcome at 90 days after ischemic stroke in placebo-treated patients enrolled in ESTAT, stratified by quartiles of fibrinogen levels measured within 6 hours of stroke onset (covariate-adjusted for age and pretreatment stroke severity).