Abstract 3103: Symptomatic Intracranial Hemorrhage Following Intravenous Thrombolysis For Acute Ischemic Stroke: A Critical Review Of Case Definitions
Background: Symptomatic intracranial hemorrhage (SICH) is the most feared complication of intravenous recombinant tissue plasminogen activator (rtPA). Differences exist in the criteria used to define neurologic decline, cerebral hemorrhage and interval between rtPA treatment and onset of cerebral hemorrhage.
Methods: We performed a systematic review to investigate SICH rates following rtPA treatment and assess their consistency with respect to mortality rates reported in the literature. Studies were identified from the PubMed and EMBASE databases from January 1994 to June 2011 by cross-referencing the following MeSH terms: “thrombolysis”, “recombinant tissue plasminogen activator”, “rtPA”, “TPA”, “Alteplase”, “thrombolytics”, “cerebral ischemia” and “stroke”. We restricted our selection to stroke registries and larger cohort studies that comprised consecutively recruited stroke patients with an operational cutoff of >200 subjects. Studies that (1) involve endovascular-treated patients, (2) applied pre-selection criteria (e.g. the presence of demonstrable arterial occlusion and pretreatment MRI), and (3) did not report both SICH and mortality rates, were excluded. We calculated the age, baseline NIHSS scores, time from stroke onset to rtPA treatment, SICH and mortality rates using published data from these studies.
Results: The initial search identified 3538 studies which were reduced to 211 potentially eligible studies that were relevant to our investigation. After application of exclusion criteria, 7 clinical trials, 7 stroke registries and 10 cohort studies (4 multi-center and 6 single-center) were included in this analysis. The mean (SD) age of these patients is 68.8 years (2.9), of whom 56.3% (4.5%) were men. These patients presented with mean baseline NIHSS 12.5 (1.4) and received intravenous rtPA 175 (62) minutes from stroke onset. The mean SICH and mortality rates were 5.6% (2.3%) and 14.7% (4.8%) respectively. Higher SICH rates were reported in randomized controlled trials (mean, 7.45%) compared with those in stroke registries (mean, 3.50%). Studies that defined SICH as parenchymal hemorrhage with neurologic decline NIHSS≥4 occurring within 36 hours of rtPA treatment have a higher consistency between SICH and mortality rates (correlation coefficient, 0.631).
Conclusion: We highlight several inconsistencies in the criteria used to define the neurologic decline, neuroimaging classification and interval between rtPA treatment and cerebral hemorrhage. These discrepancies may, in part, explain the rather striking disparities between SICH and mortality rates reported in randomized controlled trials, stroke registries and cohort studies.
- © 2012 by American Heart Association, Inc.