Trends in incidence of oral anticoagulant-related intracerebral hemorrhage and sales of oral anticoagulants in Capital Region of Denmark 2010-2017.
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ABSTRACT: Introduction
Non-vitamin K-antagonist oral anticoagulants (NOAC) have become first choice oral anticoagulant (OAC) with decreasing use of vitamin K antagonists (VKA), partly due to lower risk of intracerebral hemorrhage (ICH). Aim: to identify trends in sale of OACs and relate them to trends in OAC-related ICH (OAC-ICH).Patients and methods
Study was based on the population in the Capital Region of Denmark (1.8 million inhabitants). We identified all patients admitted with a non-traumatic OAC-ICH in 2010-2017 and ascertained diagnosis and drug use through medical charts. We used information available in the public domain on sale of defined daily doses (DDD) of OAC in the Capital Region of Denmark.Results
453 patients with OAC-ICH out of a total of 2877 ICH-events were identified. From 2010 to 2017 sale of NOAC rose from 0.1 to 11.8 DDD/1000 inhabitants/day (p < 0.001); while VKA sale decreased from 7.6 to 5.2 DDD/1000 inhabitants/day (p < 0.001). The total number of ICH events was stable between 2010 and 2017, but the proportion of OAC-ICH events increased from 13% in 2010 to 22% in 2017 (p < 0.001). The proportion of ICH events related to NOAC had a significant increasing trend (p < 0.001), whereas a decreasing trend was observed for VKA (p = 0.04).Discussion
In Denmark, the population on OACs has increased; resulting from increased use of NOACs. Parallel to this development, the proportion of OAC-ICH overall has increased based on an increasing trend in NOAC-related ICH.Conclusion
Our findings document a need for further research on prevention and treatment of this complication.
SUBMITTER: Grundtvig J
PROVIDER: S-EPMC8370066 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and purposeThe intracerebral hemorrhage (ICH) score is the most widely used and validated prognostic model for estimating 30-day mortality in ICH. However, the score was developed and validated in an ICH population probably not using oral anticoagulants (OACs). The aim of this study was to determine the performance of the ICH score for predicting the 30-day mortality rate in the full range of ICH scores in patients using OACs.MethodsData from admitted patients with ICH were collected retrospectively in two Dutch comprehensive stroke centers. The validity of the ICH score was evaluated by assessing both discrimination and calibration in OAC and OAC-naive patient groups.ResultsA total of 1752 patients were included of which 462 (26%) patients were on OAC. The 30-day mortality was 54% for the OAC cohort and 34% for the OAC-naive cohort. The 30-day mortality was higher in the OAC cohort for ICH score 1 (33% vs. 12.5%; odds ratio, 3.4; 95% confidence intervals, 1.1-10.4) and ICH score 2 (53% vs. 26%; odds ratio, 3.2; 95% confidence intervals, 1.2-8.2) compared with the predicted mortality rate of the original ICH score. Overall, the discriminative ability of the ICH score was equally good in both cohorts (area under the curve 0.83 vs. 0.87, respectively).ConclusionsThe ICH score underestimated the 30-day mortality rate for lower ICH scores in OAC-ICH. When estimating the prognosis of ICH in patients using OAC, this underestimation of mortality must be taken into account.
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Project description:ObjectiveTo compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH.MethodsIn this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors.ResultsWe compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037).ConclusionsIn this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH.
| S-EPMC4776084 | biostudies-literature
Project description:BackgroundThere is a need to examine the effects of different types of oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) on perihematomal edema (PHE), which is gaining considerable appeal as a biomarker for secondary brain injury and clinical outcome.MethodsIn a large multicenter approach, computed tomography-derived imaging markers for PHE (absolute PHE, relative PHE (rPHE), edema expansion distance (EED)) were calculated for patients with OAC-ICH and NON-OAC-ICH. Exploratory analysis for non-vitamin-K-antagonist OAC (NOAC) and vitamin-K-antagonists (VKA) was performed. The predictive performance of logistic regression models, employing predictors of poor functional outcome (modified Rankin scale 4-6), was explored.ResultsOf 811 retrospectively enrolled patients, 212 (26.14%) had an OAC-ICH. Mean rPHE and mean EED were significantly lower in patients with OAC-ICH compared to NON-OAC-ICH, p-value 0.001 and 0.007; whereas, mean absolute PHE did not differ, p-value 0.091. Mean EED was also significantly lower in NOAC compared to NON-OAC-ICH, p-value 0.05. Absolute PHE was an independent predictor of poor clinical outcome in NON-OAC-ICH (OR 1.02; 95%CI 1.002-1.028; p-value 0.027), but not in OAC-ICH (p-value 0.45).ConclusionQuantitative markers of early PHE (rPHE and EED) were lower in patients with OAC-ICH compared to those with NON-OAC-ICH, with significantly lower levels of EED in NOAC compared to NON-OAC-ICH. Increase of early PHE volume did not increase the likelihood of poor outcome in OAC-ICH, but was independently associated with poor outcome in NON-OAC-ICH. The results underline the importance of etiology-specific treatment strategies. Further prospective studies are needed.
| S-EPMC8196746 | biostudies-literature
Project description:ImportanceAlthough the use of factor Xa (FXa) inhibitors has increased substantially over the past decade, there are limited data on characteristics and outcomes of FXa inhibitor-associated intracerebral hemorrhage (ICH).ObjectiveTo investigate the association between prior oral anticoagulant use (FXa inhibitors, warfarin, or none) and in-hospital outcomes among patients with nontraumatic ICH.Design, setting, and participantsThis is a cohort study of 219 701 patients with nontraumatic ICH admitted to 1870 hospitals in the Get With The Guidelines-Stroke registry between October 2013 and May 2018. Data analysis was performed in December 2019.ExposuresAnticoagulation therapy before ICH.Main outcomes and measuresThe primary outcome was in-hospital mortality. Secondary outcomes were a composite measure of in-hospital mortality or discharge to hospice, discharge home, independent ambulation, and modified Rankin Scale (mRS) score at discharge.ResultsOf 219 701 patients (mean [SD] age, 68.2 [15.3] years; 104 940 women [47.8%]), 9202 (4.2%) were taking FXa inhibitors, 21 430 (9.8%) were taking warfarin, and 189 069 (86.0%) were not taking any oral anticoagulant before ICH. Patients taking FXa inhibitors or warfarin were older and had higher prevalence of cardiovascular risk factors. Compared with those not taking an oral anticoagulant (42 660 of 189 069 patients [22.6%]), the in-hospital mortality risk was higher for both FXa inhibitors (2487 of 9202 patients [27.0%]; adjusted odds ratio [aOR], 1.27; 95% CI, 1.20-1.34; P < .001) and warfarin (7032 of 21 430 patients [32.8%]; aOR, 1.67; 95% CI, 1.60-1.74; P < .001). Both FXa inhibitors (3478 of 9202 patients [37.8%]; aOR, 1.19; 95% CI, 1.13-1.26; P < .001) and warfarin (9151 of 21 430 patients [42.7%]; aOR, 1.50; 95% CI, 1.44-1.56; P < .001) were associated with higher odds of death or discharge to hospice compared with not taking oral anticoagulation (58 022 of 189 069 patients [30.7%]). Although the rates of discharge home, independent ambulation, mRS scores of 0 or 1, and mRS scores of 0 to 2 were numerically lower among patients taking FXa inhibitors, these differences were not significant compared with patients not taking oral anticoagulants. In contrast, patients taking FXa inhibitors were less likely to die (aOR, 0.76; 95% CI, 0.72-0.81; P < .001) or to experience death or discharge to hospice (aOR, 0.79; 95% CI, 0.75-0.84; P < .001), more likely to be discharged home (aOR, 1.18; 95% CI, 1.10-1.26; P < .001), and had better mRS scores at discharge (eg, mRS scores of 0-1: aOR, 1.24; 95% CI, 1.09-1.40; P < .001) than those treated with warfarin. Concomitant warfarin and antiplatelet therapy (either single or dual) was associated with worse outcomes compared with taking warfarin alone (eg, in-hospital mortality for dual-antiplatelet agents: aOR, 2.07; 95% CI, 1.72-2.50; P < .001). However, such incremental risk was not significant in patients taking FXa inhibitors.Conclusions and relevanceIn this cohort study, FXa inhibitor-associated ICH was associated with higher risk of mortality or death or discharge to hospice than not taking an oral anticoagulant, but patients taking FXa inhibitors had better outcomes than those with warfarin-related ICH.
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Project description: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.
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Project description:Background and aimsIntracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) usage confers significant mortality/disability. We aimed to understand the clinical and neuroimaging features associated with developing ICH among DOAC users.MethodsClinical and radiological data were collected from consecutive DOAC users with ICH (DOAC-ICH) and age-matched controls without ICH from a single referral center. The frequency/distribution of MRI markers of hemorrhage risk were assessed. Baseline demographics and neuroimaging markers were compared in univariate tests. Significant associations (p < 0.1) were entered into a multivariable regression model to determine predictors of ICH.Results86 DOAC-ICH and 94 ICH-free patients were included. Diabetes, coronary artery disease, prior ischemic stroke, smoking history, and antiplatelet usage were more common in ICH patients than ICH-free DOAC users. In the neuroimaging analyses, severe white matter hyperintensities (WMHs), lacunes, cortical superficial siderosis (cSS), and cerebral microbleeds (CMBs) were more common in the ICH cohort than the ICH-free cohort. In the multivariable regression, diabetes [OR 3.53 95% CI (1.05-11.87)], prior ischemic stroke [OR 14.80 95% CI (3.33-65.77)], smoking history [OR 3.08 95% CI (1.05-9.01)], CMBs [OR 4.07 95% CI (1.45-11.39)], and cSS [OR 39.73 95% CI (3.43-460.24)] were independently associated with ICH.ConclusionsRisk factors including diabetes, prior stroke, and smoking history as well as MRI biomarkers including CMBs and cSS are associated with ICH in DOAC users. Although screening MRIs are not typically performed prior to initiating DOAC therapy, these data suggest that patients of high-hemorrhagic risk may be identified.
| S-EPMC10947801 | biostudies-literature
Project description:BackgroundLupus anticoagulants (LA) are one laboratory criterion for classification of antiphospholipid syndrome, with presence of vascular thrombosis and/or pregnancy/fetal morbidity being clinical criteria. The presence of LA is detected (or excluded) by laboratory testing, with the activated partial thromboplastin time and dilute Russell's viper venom time the most commonly used tests. Given the association of thrombosis with LA, it is no surprise that anticoagulants are used to treat or manage such patients.ObjectivesTo review and discuss interferences from anticoagulants on LA testing, and strategies to mitigate these.MethodsThis narrative review assessed interference from commonly used anticoagulants, focusing on LA testing while on direct oral anticoagulants (DOACs), including use of DOAC neutralizers.ResultsThe classical anticoagulants comprise vitamin K antagonists such as warfarin, and heparins, predominantly unfractionated heparin and low molecular weight heparin (LMWH). DOACs have emerged with favorable efficacy and safety. These comprise two classes: direct anti-thrombin (anti-IIa; dabigatran) or direct anti-Xa (rivaroxaban, apixaban, edoxaban) agents. All anticoagulants affect clotting assays, although there are differences in effects according to anticoagulant and assay. Nevertheless, because of such interferences, anticoagulants can lead to false-negative or false-positive LA findings. Several strategies can mitigate such interferences, including avoidance of testing while patients are on such anticoagulants, temporarily switching to an anticoagulant (i.e., LMWH) with less assay interference, testing for LA at nadir levels of anticoagulants, and/or use of anticoagulant neutralizers.ConclusionWhilst the best approach is to avoid LA testing on patients taking anticoagulants; if unavoidable, testing may be facilitated by various mitigating strategies.
| S-EPMC8922544 | biostudies-literature
Project description:IntroductionDirect oral anticoagulant (DOAC)-associated intracerebral hemorrhage (ICH) is a catastrophic complication. The aim of this study was to investigate the association between computed tomography (CT)-based cerebrovascular small vessel disease (SVD) burden and DOAC-ICH as well as the DOAC concentration upon hospital admission and ICH outcome.Patients and methodsThe study included two cohorts: (1) DOAC-ICH: patients who suffered from DOAC-ICH and underwent drug level measurements upon admission; (2) DOAC-non-ICH: stable DOAC users who underwent head CT without ICH during treatment. We categorized the DOAC levels of the DOAC-ICH patients as low (<50 ng/mL), medium (50-300 ng/mL), and high (>300 ng/mL). The CT-based SVD burden (including white matter lesions [WML], lacunes, and cerebral atrophy) was evaluated, and SVD scores (range, 0-3) were used to evaluate SVD severity.ResultsA total of 43 DOAC-ICH patients and 177 DOAC-non-ICH patients were enrolled. DOAC-ICH patients were more likely to have WML, lacunes, or cerebral atrophy compared to DOAC-non-ICH patients. After adjustment, the SVD burden was associated with DOAC-ICH, with a higher risk of more severe SVD (SVD score of 2; odds ratio [OR], 10.3 [3.17, 33.3]; score of 3; OR, 16.8 [4.50, 62.6]). The proportions of patients with high, medium, and low drug levels in the DOAC-ICH group were 16.3%, 55.8%, and 27.9%, respectively. Additionally, the high-level group displayed a larger hematoma size and had worse functional outcomes at 3 months than the other two groups.Discussion and conclusionThe severity of SVD burden was associated with DOAC-ICH. Furthermore, high DOAC levels in ICH were associated with unfavorable clinical outcomes. To address the potential selection bias from these two cohorts, a prospective study to investigate the co-contribution of drug levels and SVD to DOAC-ICH is essential.
| S-EPMC10916812 | biostudies-literature
Project description:BackgroundGiven an ageing population the incidence of both patients suffering from intracerebral hemorrhage (ICH) and those requiring oral anticoagulation will increase. Up to now there are no results from randomized trials available whether or not, and when, ICH survivors should resume OAC. This review summarizes the most important observational studies, and initiated ongoing trials, to help guiding physicians in daily routine decision making.FindingsSeveral large observational studies and meta-analyses verified that OAC resumption was associated with a significant reduction of thromboembolic complications and mortality without leading to increased rates of recurrent ICH. OAC resumption seemed further associated with improved functional recovery and favorable long-term outcome. Given the general bleeding risk reduction in patients using Non-vitamin K antagonist oral anticoagulants (NOAC) compared to Vitamin-K-antagonist (VKA), NOAC use should also be preferred after ICH, although specific comparative studies are pending. Patients with lobar ICH need special attention as these patients showed increased ICH recurrence rates, why decision making should include extended diagnostic work-up evaluating cerebral microbleed burden, cortical subarachnoid hemorrhage and superficial siderosis. Further, patients with mechanical heart valves need specific consideration as restarting VKA may be unsafe until two weeks, whereas optimal balancing of hemorrhagic with thromboembolic complications may allow earlier re-initiation one week after ICH. In patients with atrial fibrillation, resumption generally should take place between 4 and 8?weeks after ICH depending on a patient's individual risk profile. Left atrial appendage occlusion (LAAO) might represent an alternative strategy in high-risk patients. Ongoing clinical trials will clarify whether OAC resumption versus LAAO versus no antithrombotic therapy may represent the best possible secondary stroke prevention in ICH survivors with atrial fibrillation.ConclusionsAccording to observational data OAC resumption after ICH seems beneficial and safe. Ongoing clinical trials will create evidence regarding treatment effects of pharmaceutical resumption and interventional alternatives. Yet, individual decision making weighing the patient's individual thromboembolic versus hemorrhagic risks remains essential.
| S-EPMC7650131 | biostudies-literature
Project description:Although non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH).To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH.Retrospective cohort study of 141?311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals.Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival.In-hospital mortality.Among 141?311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1% women), 15?036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39?585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI, 1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, -5.7% [97.5% CI, -7.3% to -4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, -15.0% [95.5% CI, -26.3% to -3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4% vs 31.7%; ARD, -5.0% [97.5% CI, -6.8% to -3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant.Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.
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