A Score for Risk of Thrombolysis-Associated Hemorrhage Including Pretreatment with Statins

Abstract

BackgroundSymptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis with recombinant tissue-plasminogen activator (rt-PA) for acute ischemic stroke is associated with a poor functional outcome. We aimed to develop a score assessing risk of sICH including novel putative predictors—namely, pretreatment with statins and severe renal impairment.MethodsWe analyzed our local cohort (Berlin) of patients receiving rt-PA for acute ischemic stroke between 2006 and 2016. Outcome was sICH according to ECASS-III criteria. A multiple regression model identified variables associated with sICH and receiver operating characteristics were calculated for the best discriminatory model for sICH. The model was validated in an independent thrombolysis cohort (Basel).ResultssICH occurred in 53 (4.0%) of 1,336 patients in the derivation cohort. Age, baseline National Institutes of Health Stroke Scale, systolic blood pressure on admission, blood glucose on admission, and prior medication with medium- or high-dose statins were associated with sICH and included into the risk of intracranial hemorrhage score. The validation cohort included 983 patients of whom 33 (3.4%) had a sICH. c-Statistics for sICH was 0.72 (95% CI 0.66–0.79) in the derivation cohort and 0.69 (95% CI 0.60–0.77) in the independent validation cohort. Inclusion of severe renal impairment did not improve the score.ConclusionWe developed a simple score with fair discriminating capability to predict rt-PA-related sICH by adding prior statin use to known prognostic factors of sICH. This score may help clinicians to identify patients with higher risk of sICH requiring intensive monitoring.

Premorbid Use of Statin and Outcome of Acute Ischemic Stroke After Intravenous Thrombolysis: A Meta-Analysis

“…The characteristics of the included studies are presented in Table 1 . Overall, this meta-analysis included 12 prospective cohort studies ( 10 , 11 , 13 , 14 , 16 – 18 , 20 – 23 , 27 ), five retrospective cohort studies ( 9 , 12 , 15 , 19 , 26 ), and three post-hoc analyses of RCTs ( 24 , 25 , 28 ), with a total of 20,752 AIS patients who were treated with IVT. The mean ages of the included patients varied between 63 and 75 years, and the baseline NIHSS varied from 7 to 17.…”

“…Moreover, the premorbid use of statin was associated with an increased risk of SIH in AIS after IVT [16 studies ( 10 – 14 , 16 – 18 , 20 – 25 , 27 , 28 ), OR: 1.48, 95% CI: 1.12–1.95, p = 0.006, I 2 = 60%; Figure 4 ]. Consistent results were retrieved in subgroup analyses according to study design ( Figure 4A ) or adjustment of LDL-C at baseline ( Figure 4B ).…”

Prior statin use and intravenous thrombolysis in acute ischemic stroke: a meta-analysis of cohort studies

“…7 Despite the beneficial effects, some studies have shown that statins decrease platelet aggregation and thrombogenesis 8 , which may be related to symptomatic intracranial hemorrhages (sICH) and exacerbate unfavorable outcomes. 9 Some studies have reported that prior statin use (PSU) was associated with improved functional outcomes 10,11,14,17,18 , but these findings have not been consistently replicated. 12,13,15,16,19,20 Some studies have shown that statin use before thrombolysis is associated with adverse outcomes such as increased mortality and sICH.…”

The risk of symptomatic intracranial hemorrhage after thrombolysis for acute stroke: Current concepts and perspectives

“…Prior statin use has been associated to increased risk of SICH, but it did not have any impact on outcomes according to cases series of 311 and 182 patients treated[3637] and three European registries totaling 2482 patients. [373839] In another registry of 606 patients, the risk of SICH was not increased (OR: 0.57; 95% confidence interval [CI]: 0.22–1.49)[40] and in a meta-analysis of 11 studies and 6438 patients, the statin use neither increased the risk of SICH nor was associated with more favorable outcomes. [40]…”