Diverging Trends in Survival and Functional Outcome between Males and Females after Intracerebral Hemorrhage.

BACKGROUND: Compared to ischemic stroke, sex differences in patient outcomes following intracerebral hemorrhage (ICH) are underreported. We aimed to determine sex differences in mortality and functional outcomes in a large, unselected Swedish cohort. METHODS: In this observational study, data on 22,789 patients with spontaneous ICH registered in the Swedish Stroke Register between 2012 and 2019 were used to compare sex differences in 90-day mortality and functional outcome using multivariable Cox and logistic regression analyses, adjusting for relevant confounders. Multiple imputation was used to impute missing data. RESULTS: The crude 90-day mortality rate was 36.7% in females (3,820/10,405) and 31.7% in males (3,929/12,384) (female hazard ratio [HR] 1.20 95% confidence interval [CI]: 1.15-1.25). In multivariable analysis, the HR for 90-day mortality following ICH in females was 0.89 (95% CI: 0.85-0.94). Age was an important driving factor for the effect of sex on mortality. After adjustment for age, vascular risk factors, and stroke severity, the 90-day functional outcome in pre-stroke independent patients was worse in females compared to males (odds ratio: 1.27 95% CI: 1.16-1.40). CONCLUSION: In this large observational study, despite lower 90-day mortality, the female sex was independently associated with a worse functional outcome compared to males after ICH, even after adjusting for significant covariates. These diverging trends have not been previously reported for ICH. Given the observational design, our findings should be interpreted with caution, thus further external validation is warranted.

Diagnostic accuracy and radiological validation of intracerebral hemorrhage diagnosis in the Swedish Stroke Register (Riksstroke).

BACKGROUND AND PURPOSE: National quality registries for stroke care operate under the assumption that the included patients are correctly diagnosed. We aimed to validate the clinical diagnosis of spontaneous intracerebral hemorrhage (ICH) in Riksstroke (RS) by evaluating radiological data from a large, unselected ICH population. METHODS: We conducted a retrospective, multicenter study including all ICH patients registered in RS between 2016 and 2020 residing in Skåne County in Sweden (1.41 million inhabitants). Radiological data from first imaging were evaluated for the presence of spontaneous ICH. Other types of bleeds were registered if a spontaneous ICH was not identified on imaging. The radiological evaluation was independently performed by one radiology fellow and one senior neuroradiologist. RESULTS: Between 2016 and 2020, 1784 ICH cases were registered in RS, of which 1655 (92.8%) had a radiological diagnosis consistent with spontaneous ICH. In the 129 (7.2%) remaining cases, the radiological diagnosis was instead traumatic bleed (n = 80), subarachnoid hemorrhage (n = 15), brain tumor bleed (n = 14), ischemic lesion with hemorrhagic transformation (n = 14), ischemic lesion (n = 3), or no bleed at all (n = 3). There was a higher degree of incorrect coding in the older age groups. CONCLUSION: At radiological evaluation, 92.8% of ICH diagnoses in RS were consistent with spontaneous ICH, yielding a high rate of agreement that strengthens the validity of the diagnostic accuracy in the register, justifying the use of high coverage quality register data for epidemiological purposes. The most common coding error was traumatic bleeds that were classified as spontaneous ICH.

Patient factors associated with receiving reversal therapy in oral anticoagulant-related intracerebral hemorrhage.

BACKGROUND: We aimed to describe baseline characteristics of patients with oral anticoagulant-related intracerebral hemorrhage (OAC-ICH) in Sweden and to identify predictive variables associated with receiving hemostatic treatment in the event of OAC-ICH. METHODS: We performed an observational study based on data from Riksstroke and the Swedish Causes of Death Register to define baseline characteristics of patients with OAC-ICH who received reversal treatment compared with patients who did not receive reversal treatment during 2017-2019. Predictive analysis was performed using multivariable logistic regression to identify odds ratios for factors associated with receiving OAC reversal treatment. RESULTS: We included 1902 patients ((n = 1146; OAC reversal treatment) (n = 756; no OAC reversal treatment)). The proportion of non-Vitamin K oral anticoagulant associated ICH (NOAC-ICH) patients who received reversal treatment was 48.4% and the proportion of Vitamin K antagonist-associated ICH (VKA-ICH) patients was 72.9%. Factors associated with a lower odds of receiving reversal treatment were increased age (OR = 0.98; 95% CI: 0.96-0.99), previous stroke (OR = 0.78; 95% CI: 0.62-0.98), comatose LOC (OR = 0.36;95%CI: 0.27-0.48; ref. = alert), pre-stroke dependency (OR = 0.72; 95% CI: 0.58-0.91), and NOAC treatment (OR = 0.34; 95% CI: 0.28-0.42). Care at a university hospital was not associated with higher odds of receiving reversal treatment compared to treatment at a county hospital. CONCLUSION: Treatment with a reversal agent following OAC-ICH was related to several patient factors including type of OAC drug. We identified that only 48% of patients with NOAC-ICH received hemostatic treatment despite an increase in these cases. Further studies are required to guide the use of reversal therapies more precisely, particularly in NOAC-ICH.

Prognosis of Intracerebral Hemorrhage Related to Antithrombotic Use: An Observational Study From the Swedish Stroke Register (Riksstroke).

BACKGROUND AND PURPOSE: To date, large studies comparing mortality and functional outcome of intracerebral hemorrhage (ICH) during oral anticoagulant (OAC), antiplatelet, and nonantithrombotic use are few and show discrepant results. METHODS: We used data on 13 291 patients with ICH registered in Riksstroke between 2012 and 2016 to compare 90-day mortality and functional outcome following OAC-related ICH (n=2300), antiplatelet-related ICH (n=3637), and nonantithrombotic ICH (n=7354). Univariable and multivariable Cox regression analyses, with adjustment for relevant confounders, were used to compare 90-day mortality. Early (≤24 hours and 1-7 days) and late (8-90 days) mortality was also studied in subgroup analyses. Univariable and multivariable 90-day functional outcome, based on self-reported modified Rankin Scale, was determined using logistic regression. RESULTS: Patients with antithrombotic treatment were more often prestroke dependent, older, and had a larger comorbidity burden compared with patients without antithrombotic treatment. At 90 days, antiplatelet and OAC were associated with an increased death rate in multivariable analysis (antiplatelet ICH: hazard ratio, 1.23 [95% CI, 1.14-1.33]; OAC ICH: hazard ratio, 1.40 [95% CI, 1.26-1.57]) compared with nonantithrombotic ICH (reference). OAC ICH and antiplatelet ICH were associated with higher risk of early mortality (≤24 hours: OAC ICH: hazard ratio, 1.93 [95% CI, 1.57-2.38]; antiplatelet ICH: hazard ratio, 1.32 [95% CI, 1.13-1.54]). In multivariable analysis, the odds ratios for the association of antiplatelet and OAC treatment on functional dependency (modified Rankin Scale score, 3-5) at 90 days were nonsignificant (antiplatelet: odds ratio, 1.07 [95% CI, 0.92-1.24]; OAC: odds ratio, 0.96 [95% CI, 0.76-1.22]). CONCLUSIONS: In this large observational study, we found that 90-day mortality outcome was worse not only in OAC ICH but also in antiplatelet ICH, compared with patients with nonantithrombotic ICH. Antiplatelet ICH is common and is a serious condition with poor clinical outcome. Further studies are, therefore, warranted in determining the appropriate clinical management of these patients.

Prognosis for intracerebral hemorrhage during ongoing oral anticoagulant treatment.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most serious adverse effect of treatment with oral anticoagulants. Prognostic data after ICH associated with non-vitamin K antagonist oral anticoagulants (NOAC) compared to vitamin K antagonists (VKA) are sparse. We compared 90-day survival and functional outcome following NOAC-ICH versus VKA-ICH using data from the Swedish Stroke Register (Riksstroke). METHODS: Using data from Riksstroke and the Swedish Causes of Death Register between 2012 and 2016, we compared all-cause 90-day mortality for patients with NOAC-ICH versus VKA-ICH using Kaplan-Meier survival analysis and Log-rank test. Cox regression, with adjustment for age, sex, previous stroke, and level of consciousness (LOC) on admission, was used to estimate hazard ratios (HR) for 90-day mortality. Estimated functional outcome at 90 days, based on the modified Rankin Scale (mRS), was compared between VKA- and NOAC-associated ICH using chi-squared test. RESULTS: We included 2483 patients; 300 with NOAC-ICH and 2183 with VKA-ICH. In both groups, mean age was 79 years, and 58% were male. No significant difference between NOAC-ICH and VKA-ICH was found for all-cause 90-day mortality (44.3% NOAC-ICH versus 42.6% VKA-ICH; P = 0.54, HR = 0.93; 95% confidence interval (CI): 0.78-1.12) or 90-day estimated functional outcome (mRS 0-2:13.7% and 15.3%; mRS 3-5:27.3% and 28.9%, respectively (P = 0.52)). Factors predicting death were increased age (HR = 1.03; 95%CI: 1.02-1.04) and reduced LOC (drowsy: HR = 3.48; 95%CI: 2.86-4.23; comatose: HR = 12.27; 95%CI: 10.13-14.87). CONCLUSION: In this large study on anticoagulant-associated ICH, we found no significant difference in mortality and functional outcome at 90 days between NOAC-ICH versus VKA-ICH.

Reversal Treatment in Oral Anticoagulant-Related Intracerebral Hemorrhage-An Observational Study Based on the Swedish Stroke Register.

Introduction: Intracerebral hemorrhage (ICH) is the most serious adverse effect of oral anticoagulant (OAC) treatment. The effect of OAC reversal therapy on outcome is uncertain. We compared 90-day survival and functional outcome in patients with OAC-ICH who received OAC reversal therapy with those who did not. Methods: Data from The Swedish Stroke Register (Riksstroke) for all registered cases of OAC-ICH during 2017 (572 patients) were used to obtain information on reversal (n = 369) and non-reversal (n = 203) treatment receiving patients. Univariate and multivariate Cox regression analysis stratified for level of consciousness (LOC) on admission, and adjustment for relevant baseline variables, was used to compare 90-day Hazard Ratios (HR) for mortality. Results: Sixty-five percent of patients received reversal treatment. These patients were younger, more often pre-stroke independent and alert at presentation. Withholding reversal treatment was associated with an increased death rate (HR = 1.47; 95% CI: 1.08-2.01) in a Cox regression model stratified for LOC and adjusted for baseline imbalances. Additional factors associated with an increased 90-day death rate were male sex (HR = 1.42; 95% CI: 1.06-1.92), age (HR = 1.05; 95% CI: 1.02-1.07), and intraventricular hemorrhage (HR = 2.41; CI: 1.77-3.29). Conclusion: In this large observational study 35% of patients with OAC-ICH did not receive reversal treatment. Patients receiving OAC-reversal treatment had an improved 90-day mortality outcome compared to those not receiving treatment. Mortality was strongly related to LOC. Further, and larger, studies are required to determine which patient groups may benefit from reversal therapy and in whom non-reversal is adequate.