Juha Huhtakangas

Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study.

Background and Purpose— Warfarin use has rapidly increased with the aging of the population. We investigated the temporal trends in the incidence and outcome of warfarin-related intracerebral hemorrhages (ICHs) in a defined population. Methods— We identified all subjects with first-ever primary ICH during 1993 to 2008 among the population of Northern Ostrobothnia, Finland. The number of warfarin users was obtained from the national register of prescribed medicines kept by the Social Insurance Institution of Finland. We calculated the annual incidence of warfarin-related ICHs, 28-day case fatality, and deaths from the primary bleed. Results— The proportion of warfarin users among the population increased 3.6-fold from 0.68% in 1993 to 2.28% in 2008. Of a total of 982 patients with ICH, 182 (18.5%) had warfarin-related ICH. One-year survival rate after onset of stroke was 35.2% among warfarin users and 67.9% among nonusers. The annual incidence (P=0.062) and 28-day case fatality of warfarin-related ICHs (P=0.002) decreased during the observation period. Warfarin users were older (mean difference 6.6; 95% CI, 5.0 to 8.1; P<0.001) than nonusers. Admission international normalized ratio values above the therapeutic range (2.0 to 3.0) decreased through the observation period, suggesting improved control of anticoagulant therapy over time. Conclusions— The annual incidence and case fatality of warfarin-related ICHs decreased, although the proportion of warfarin users almost quadrupled in our population.

Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA‐ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different reversal strategies.

Predictors for Recurrent Primary Intracerebral Hemorrhage A Retrospective Population-based Study

Background and Purpose— Underlying comorbidities, previous strokes, and medication may increase the risk for primary intracerebral hemorrhage (PICH) and its recurrence. The aim of this study was to determine the independent predictors for recurrent PICH. Methods— We identified 961 subjects with first-ever PICH from 1993 to 2008 among the population of Northern Ostrobothnia, Finland. Hospital and death records were reviewed and data on drug use were obtained from the national register of prescribed medicines. Kaplan–Meier survival curves and Cox proportional hazards models were used to demonstrate predictors for recurrence of PICH. Results— Total follow-up time of the 961 patients was 3481 person-years. During the follow-up time, 58 subjects had altogether 68 recurrent PICHs. The annual average incidence of first recurrence was 1.67%. Cumulative 5- and 10-year incidence rates were 9.6% and 14.2%, respectively. In univariable analysis, history of ischemic stroke, diabetes mellitus, and aspirin use were associated with a higher recurrence rate. In multivariable analysis, only previous ischemic stroke (adjusted hazard ratio, 2.22; 95% confidence interval, 1.22–4.05; P=0.009) independently predicted PICH recurrence. Diabetes mellitus tended to increase (adjusted hazard ratio, 2.38; 95% confidence interval, 0.98–5.80; P=0.056), whereas treated hypertension tended to decrease (0.45, 0.20–1.01; P=0.054) the risk for fatal recurrent PICH. Conclusions— Previous ischemic stroke independent of confounding factors may increase the risk for PICH recurrence.

Improved survival of patients with warfarin-associated intracerebral haemorrhage: a retrospective longitudinal population-based study

Background Warfarin-associated intracerebral haemorrhage carries poor outcome due to rapid haemorrhage growth. Reversal of warfarin anticoagulation with prothrombin complex concentrate has been implemented as an acute treatment option for these subjects. Aim We investigated whether survival of subjects with warfarin-associated intracerebral haemorrhage had improved after implementation of reversal of warfarin anticoagulation with prothrombin complex concentrate. Methods We identified all subjects with warfarin-associated intracerebral haemorrhage during 1993–2008 among the population of Northern Ostrobothnia, Finland. From 2004 onwards, prothrombin complex concentrate was used in Oulu University Hospital, the only hospital treating intracerebral haemorrhage subjects in the region, to counteract the effect of warfarin in subjects with warfarin-associated intracerebral haemorrhage. We compared the outcomes of subjects admitted during 1993–2003 and 2004–2008 and those treated and not treated with prothrombin complex concentrate. We also explored the predictors for one-year survival of the warfarin-associated intracerebral haemorrhage subjects. Results We identified altogether 181 subjects who had intracerebral haemorrhage while on warfarin. One-year survival was significantly (P = 0·031) higher for the 60 subjects admitted during 2004–2008 (43·3%) than for the 121 admitted before 2004 (30·6%). In multivariable analysis, prothrombin complex concentrate treatment reduced one-year case fatality (hazard ratio 0·52, 95% confidence interval 0·29–0·93). Thromboembolic complications did not occur more frequently among those treated with prothrombin complex concentrate. Conclusion The survival of warfarin-associated intracerebral haemorrhage subjects among the population of Northern Ostrobothnia has improved likely because of introduction of prothrombin complex concentrate.

Predictive value of C-reactive protein for the outcome after primary intracerebral hemorrhage

OBJECT Primary intracerebral hemorrhage (ICH) carries high morbidity and mortality rates. Several factors have been suggested as predicting the outcome. The value of C-reactive protein (CRP) levels in predicting a poor outcome is unclear, and findings have been contradictory. In their population-based cohort, the authors tested whether, independent of confounding factors, elevated CRP levels on admission (< 24 hours after ictus) are associated with an unfavorable outcome. METHODS The authors identified all patients who suffered primary ICH between 1993 and 2008 among the population of Northern Ostrobothnia, Finland, and from the laboratory records they extracted the CRP values at admission. Independent predictors of an unfavorable outcome (moderate disability or worse according to the Glasgow Outcome Scale at 3 months) were tested by unconditional logistic regression in a model including all the well-established confounding factors and CRP on admission. RESULTS Of 961 patients, 807 (84%) had CRP values available within 24 hours of admission, and multivariable analysis showed elevated CRP at that point to be associated with an unfavorable outcome (OR 1.41 per 10 mg/L [95% CI 1.09-1.81], p < 0.01), together with diabetes mellitus (OR 1.99 [95% CI 1.09-3.64], p < 0.05), age (1.06 per year [95% CI 1.04-1.08], p < 0.001), low Glasgow Coma Scale score (0.75 per unit [95% CI 0.67-0.84], p < 0.001), hematoma size (1.05 per ml [95% CI 1.03-1.07], p < 0.001), and the presence of an intraventricular hemorrhage (2.70 [95% CI 1.66-4.38], p < 0.001). Subcortical location predicted a favorable outcome (0.33 [95% CI 0.20-0.54], p < 0.001). CONCLUSIONS Elevated CRP on admission is an independent predictor of an unfavorable outcome and is only slightly associated with the clinical and radiological severity of the bleeding.

Better than expected survival after primary intracerebral hemorrhage in patients with untreated hypertension despite high admission blood pressures

Background:  Hypertension is the most important modifiable risk factor for primary intracerebral hemorrhage (ICH), but little is known of the effect of preceding hypertension on outcome. Because high mean arterial blood pressure (MABP) at admission is an independent predictor of early death in patients with ICH, we explored its role on survival and poor outcome separately in normotensive subjects and subjects with treated and untreated hypertension.

Association between warfarin combined with serotonin-modulating antidepressants and increased case fatality in primary intracerebral hemorrhage: a population-based study

OBJECT Patients receiving oral anticoagulants run a higher risk of cerebral hemorrhage with a poor outcome. Serotonin-modulating antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs]) are frequently used in combination with warfarin, but it is unclear whether this combination of drugs influences outcome after primary intracerebral hemorrhage (PICH). The authors investigated case fatality in PICH among patients from a defined population who were receiving warfarin alone, with aspirin, or with serotonin-modulating antidepressants. METHODS Nine hundred eighty-two subjects with PICH were derived from the population of Northern Ostrobothnia, Finland, for the years 1993-2008, and those with warfarin-associated PICH were eligible for analysis. Their hospital records were reviewed, and medication data were obtained from the national register of prescribed medicines. Kaplan-Meier survival curves were drawn to illustrate cumulative case fatality, and a Cox proportional-hazards analysis was performed to demonstrate predictors of death. RESULTS Of the 176 patients eligible for analysis, 17 had been taking aspirin and 19 had been taking SSRI/SNRI together with warfarin. The 30-day case fatality rates were 50.7%, 58.8%, and 78.9%, respectively, for those taking warfarin alone, with aspirin, or with SSRI/SNRI (p = 0.033, warfarin plus SSRI/SNRI compared with warfarin alone). Warfarin combined with SSRI/SNRI was a significant independent predictor of case fatality (adjusted HR 2.10, 95% CI 1.13-3.92, p = 0.019). CONCLUSIONS Concurrent use of warfarin and a serotonin-modulating antidepressant, relative to warfarin alone, seemed to increase the case fatality rate for PICH. This finding should be taken into account if hematoma evacuation is planned.

Immediate, early and late seizures after primary intracerebral hemorrhage

BACKGROUND Seizures after primary intracerebral hemorrhage (PICH) are significant and treatable complications, but the factors predicting immediate, early and late seizures are poorly known. We investigated characteristics and outcome with special reference to occurrence and timing of a first seizure among consecutive subjects with PICH. METHODS A population-based study was conducted in Northern Ostrobothnia, Finland, in 1993-2008 that included all patients with a first-ever primary ICH without any prior diagnosis of epilepsy. Immediate (<24h after admission), early (1-14 days) and late (>2 weeks) seizures were considered separately. RESULTS Out of a total of 935 ICH patients, 51 had immediate, 21 early and 58 late seizures. The patients with seizures were significantly younger than the others and more often had a subcortical hematoma location (p<0.05). Lifestyle factors did not differ between the groups. The risk factors for immediate seizures in multivariable analysis were a low Glasgow coma scale score (GCS) on admission, subcortical location and age inversely (p<0.01). The only independent risk factor for early seizures was subcortical location (p<0.001), whereas subcortical location (p<0.001), age inversely (p<0.01) and hematoma evacuation (p<0.05) independently predicted late seizures. Immediate and early seizures predicted infectious complications (p<0.05). CONCLUSIONS Patients with subcortical hematoma and of younger age are at risk for immediate seizures after primary ICH irrespective of hematoma size. Patients with immediate and early seizures more often had infectious complications. Surgery increases the risk of a late seizure after ICH.

Poststroke epilepsy in long-term survivors of primary intracerebral hemorrhage

Objective: To identify the incidence and predisposing factors for development of poststroke epilepsy (PSE) after primary intracerebral hemorrhage (PICH) during a long-term follow-up. Methods: We performed a retrospective study of patients who had had their first-ever PICH between January 1993 and January 2008 in Northern Ostrobothnia, Finland, and who survived for at least 3 months. These patients were followed up for PSE. The associations between PSE occurrence and sex, age, Glasgow Coma Scale (GCS) score on admission, hematoma location and volume, early seizures, and other possible risk factors for PSE were assessed using the Cox proportional hazards regression model. Results: Of the 615 PICH patients who survived for longer than 3 months, 83 (13.5%) developed PSE. The risk of new-onset PSE was highest during the first year after PICH with cumulative incidence of 6.8%. In univariable analysis, the risk factors for PSE were early seizures, subcortical hematoma location, larger hematoma volume, hematoma evacuation, and a lower GCS score on admission, whereas patients with infratentorial hematoma location or hypertension were less likely to develop PSE (all variables p < 0.05). In multivariable analysis, we found subcortical location (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.35–3.81, p < 0.01) and early seizures (HR 3.63, 95% CI 1.99–6.64, p < 0.01) to be independent risk factors, but patients with hypertension had a lower risk of PSE (HR 0.54, 0.35–0.84, p < 0.01). Conclusions: Subcortical hematoma location and early seizures increased the risk of PSE after PICH in long-term survivors, while hypertension seemed to reduce the risk.

A population based study of outcomes after evacuation of primary supratentorial intracerebral hemorrhage.

BACKGROUND AND PURPOSE The role of surgery after primary intracerebral hemorrhage (ICH) is controversial. To explore whether hematoma evacuation after ICH had improved short-term survival or functional outcome we conducted a retrospective observational population-based study. METHODS We identified all subjects with primary ICH between 1993 and 2008 among the population of Northern Ostrobothnia, Finland. Hematoma evacuation was carried out by using standard craniotomy or through a burr hole. We compared mortality rates and functional outcomes of patients with hematoma evacuation with those treated conservatively. RESULTS Of 982 patients with verified ICH during the study period, 127 (13%) underwent hematoma evacuation. Surgically treated patients were significantly younger (mean±SD, 63±11 vs. 70±12 years; p<0.001), had larger hematomas (66±36 vs. 28±40 ml; p<0.001), lower Glasgow Coma Scale scores (median, 11 vs. 14; p<0.001) and more frequently subcortical hematomas (68% vs. 24%; p<0.001) than those treated conservatively. In multivariable analysis, hematoma evacuation independently lowered 3-month mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.43-0.88; p<0.03), particularly among patients aged≤70 years with ≥30 ml supratentorial hematomas (adjusted HR, 0.26; 95% CI, 0.14-0.49; p<0.001). However, poor outcome was not improved by surgery (adjusted odds ratio 0.71; 95% CI 0.29-1.70). CONCLUSIONS Improved 3-month survival was observed in patients who had undergone hematoma evacuation relative to patients not undergoing evacuation particularly in the subgroup of patients aged≤70 years with ≥30 ml supratentorial hematomas. Surgery might improve outcome if cases could be selected more precisely and if performed before deterioration.