Warfarin-associated Intracerebral Hemorrhage is Increasing in Prevalence in the United States
ABSTRACT BACKGROUND: Warfarin-associated intracerebral hemorrhage (WAICH) is expected to increase in prevalence as the population ages. We sought to evaluate national trends, characteristics, and in-hospital outcomes among intracerebral hemorrhage (ICH) patients taking warfarin at baseline. METHODS: We reviewed the Nationwide Inpatient Sample to identify all admissions with primary diagnosis of ICH by International Classification of Diseases, Ninth Revision code (431) from 2005 to 2008. We identified premorbid warfarin use by the V code (V58.93) and calculated the proportion of WAICH among all ICH patients in each year. We employed univariate statistics and generalized estimating equation regression models to assess whether warfarin use independently increased the risk of in-hospital mortality after adjusting for relevant covariates. P value less than .05 was considered significant. RESULTS: There were 52,993 patients (mean age 68.8 years; 49.7% male) coded for ICH between 2005 and 2008. The proportion with WAICH increased each year (2005, 5.8%; 2006, 6.5%; 2007, 6.9%; 2008, 7.3%; P < .001). While in-hospital mortality declined each year for non-WAICH (29.0%-25.4%, P < .001), it remained unchanged for WAICH (42.1%-40.0%, P = .346). In multivariable analysis, warfarin use (adjusted odds ratio 1.35; 95% confidence interval 1.24-1.47) remained an independent predictor of in-hospital mortality. CONCLUSIONS: WAICH is increasing in prevalence in the United States and is associated with a 35% higher mortality than non-WAICH. While mortality has declined over time for non-WAICH, mortality after WAICH is unchanged. Specific strategies to decrease the mortality of WAICH such as rapid reversal of anticoagulation are warranted.
- [Show abstract] [Hide abstract]
ABSTRACT: OBJECTIVE: The aim of the study was to analyse non-warfarin-associated bleeding adverse drug events reported to the Norwegian spontaneous reporting system, with characterisation of the bleeding locations, outcome and drug interactions. In addition, concordance in assessments between reporters and evaluators, trend shifts in reporting, and detection of potentially new adverse drug interaction signals were studied. METHODS: Data on bleeding events reported between 1 January 2003 and 31 December 2005 were retrieved from the Norwegian spontaneous reporting system database. RESULTS: Of 327 case reports of non-warfarin-associated bleeding events, 270 reports (82.6 %) were characterised as serious and 69 (21.1 %) had a fatal outcome. One hundred and eighty-seven bleeds (57.5 %) were gastrointestinal, 57 (17.4 %) were cerebral, and 81 (24.8 %) were from other bleeding sites. The bleeding sites differed with respect to the patient's age, drug use, diagnoses and outcomes. Of drugs associated with bleeding, nonsteroidal anti-inflammatory drugs (NSAIDs)/COX-2 inhibitors (145 reports) and acetylsalicylic acid (128 reports) were most frequently used. Only fibrinolytics were associated with increased mortality. There was a 67.4 % correlation between reporters and evaluators in assessment of drugs associated with bleeding (P < 0.001), with considerable variation in concordance between drug groups. CONCLUSION: Non-warfarin-associated bleeding events are associated with substantial mortality. Old age, cerebral bleeds, number of drugs used, and use of fibrinolytics are all independently associated with increased mortality. The recognition of the bleeding risk of commonly used drugs such as acetylsalicylic acid and heparins may be insufficient among prescribers.European Journal of Clinical Pharmacology 02/2013; 69(7). DOI:10.1007/s00228-013-1479-7 · 2.70 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Bleeding symptoms are frequently reported even in otherwise healthy subjects, and differentiating a normal subject from a patient with a mild bleeding disorder (MBD) can be extremely challenging. The concept of bleeding rate, that is, the number of bleeding episodes occurring within a definite time, could be used as the unifying framework reconciling the bleeding risk observed in congenital and acquired coagulopathies into a single picture. For instance, primary prevention trials have shown that the incidence of non-major bleeding symptoms in normal subjects is around five per 100 person-years, and this figure is in accordance with the number of hemorrhagic symptoms reported by normal controls in observational studies on hemorrhagic disorders. The incidence of non-major bleeding in patients with MBDs (e.g. in patients with type 1 VWD carrying the C1130F mutation) is also strikingly similar with that of patients taking antiplatelet drugs, and the incidence in moderately severe bleeding disorders (e.g. type 2 VWD) parallels that of patients taking vitamin K antagonists. The severity of a bleeding disorder may therefore be explained by a bleeding rate model, which also explains several common clinical observations. Appreciation of the bleeding rate of congenital and acquired conditions and of its environmental/genetic modifiers into a single framework will possibly allow the development of better prediction tools in the coming years and represents a major scientific effort to be pursued.Journal of Thrombosis and Haemostasis 06/2013; 11(s1). DOI:10.1111/jth.12248 · 5.55 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Warfarin-associated intracerebral hemorrhage (WICH) is a serious neurological condition associated with significant mortality and morbidity. We aimed to study the clinical features and factors that predict clinical outcome of Chinese patients with WICH.METHODS: Medical records of patients with spontaneous intracerebral hemorrhage (ICH) admitted to our hospital between July 2001 and June 2010 were reviewed and those with WICH were studied in detail retrospectively.RESULTS: About 51 patients with WICH were identified. The mean age was 74.3 ± 10.5 years and 52.9% of the patients were female. The mean international normalized ratio (INR) on presentation was 2.9 ± 1.0. The median ICH volume was 23.3 (10.4?59.3) ml. The mortality rate at 3?6 months for WICH was 62.0%. Multivariate logistic analysis revealed that an initial ICH volume of > 20 ml (OR 34.4, P = 0.037) and presence of intraventricular hemorrhage (OR 22.9, P = 0.046) were independently associated with poor outcome. Supratherapeutic INR (INR > 3.0) on admission (P = 0.724) and complete correction of INR within 24 hours after admission (P = 0.486) were not independent predictors of poor outcome. The median ICH volumes did not differ between INR groups (18.2 (9.4?61.1) ml for INR ≤ 3 vs 27.3 (13.7?58.5) ml for INR > 3, P = 0.718). Neurological deterioration (ND) was documented in 19 (63.3%) of the 30 patients included in a smaller sub-cohort, and was associated with poor neurological outcome (OR 20.7, P = 0.027). Warfarin was resumed in 7 of the 20 survivors. There were two episodes of recurrent WICH and one episode of ischemic stroke during a mean follow-up duration of 5.4 years. In survivors who were not resumed on warfarin, there were two episodes of recurrent ICH and 12 episodes of ischemic vascular events (nine ischemic strokes) during a mean follow-up duration of 2.6 years.CONCLUSION: Warfarin-associated intracerebral hemorrhage is a very serious complication of warfarin therapy with high mortality and morbidity. Initial ICH volume, presence of intraventricular hemorrhage, and ND are independent predictors of clinical outcome.Neurological Research 10/2013; 36(2). DOI:10.1179/1743132813Y.0000000275 · 1.45 Impact Factor