History of Intracranial Hemorrhage Is Associated with In-Hospital Mortality in Ischemic Stroke Patients Treated with Intravenous Thrombolytics

Aims: The recently updated FDA label removed history of intracranial hemorrhage (ICH) from its list of contraindications, possibly due to lack of data on risks and benefits. In a survey of US stroke clinicians, just over 10% reported willingness to treat patients with a history of ICH with intravenous tissue plasminogen activator (IV-tPA). Our objective was to evaluate whether history of ICH increases in-hospital mortality in acute ischemic stroke (AIS) patients treated with IV-tPA.

Methods: We performed a retrospective analysis of prospectively collected administrative claims data on discharges from California hospitals between 2005 and 2011 from the Healthcare Cost and Utilization Project State Inpatient Database. Subjects were adult patients admitted for the first time with AIS and received IV-tPA. We used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify stroke patients and those with the exposure of interest, history of ICH. The primary outcome was in-hospital mortality of any cause. The secondary outcome was disposition at discharge. We used multivariable logistic regression to model the risk of in-hospital death in ischemic stroke patients who received IV-tPA as a function of prior ICH status, after adjusting for potential confounders, including demographic and medical risk factors.

Results: A total of 11,259 patients who received IV-tPA during first-time AIS admissions were included in the study (mean age 71 [standard deviation 14], female 5,660 [50.3%]). Among these, 246 (2.2%) had prior diagnoses of ICH, including spontaneous intraparenchymal hemorrhage (n = 158), subarachnoid hemorrhage (n = 72), subdural hemorrhage (n = 7), and multicompartmental hemorrhage (n = 9). In-hospital mortality of any cause was 12.9% (n = 1,455) overall, 12.6% (n = 1,387) for patients without a history of ICH, and 27.6% (n = 68) for patients with a history of ICH. In adjusted analyses, history of ICH remained independently associated with in-hospital mortality (odds ratio [OR] 3.04, 95% confidence interval [CI] 2.27–4.02; p 2E-14), as did the ICH subtypes intraparenchymal hemorrhage (OR 2.27, CI 1.58–3.21; p 5E-6) and subarachnoid hemorrhage (OR 4.34, CI 2.64–6.97; p 3E-9).

Conclusions: In a large population of AIS patients treated with IV-tPA, a prior history of ICH was independently associated with increased in-hospital mortality. Further studies, including randomized clinical trials, are needed to definitively establish the safety of IV-tPA treatment in AIS patients. Caution should be exercised when considering treatment with intravenous thrombolytics in patients with an AIS who have history of ICH.