Dataset Information

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study.

ABSTRACT:

Background

Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants.

Methods

We used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period.

Results

A total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12%, respectively.

Interpretation

We observed increasing time trends in intracranial bleeding, both associated with and not associated with oral anticoagulants, over the study period. Although aggregate provincial data showed increased prescribing of oral anticoagulants, other more likely explanations for our findings include an aging population or increasing frailty.

SUBMITTER: Hogg K

PROVIDER: S-EPMC4701652 | biostudies-literature | 2015 Oct-Dec

REPOSITORIES: biostudies-literature

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Publications

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study.

Hogg Kerstin K Bahl Bharat B Latrous Meriem M Scaffidi Argentina Sarina S Thompson Jesse J Chatha Aasil Ayyaz AA Castellucci Lana L Stiell Ian G IG

CMAJ open 20151001 4

<h4>Background</h4>Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants.<h4>Methods</h4>We used ICD-1 ...[more]

PMID: 26770966

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Project description:Background and purposeThe use of direct oral anticoagulants (DOAC) has increased sharply and DOAC are the oral anticoagulant therapy (OAT) of choice for the majority of patients with newly-diagnosed atrial fibrillation. Intracranial hemorrhage is the most severe adverse event of OAT. Systematic data on the course of intracranial hemorrhage under DOAC compared to vitamin K antagonists (VKA) are warranted to enable shared decision making in AF patients needing OAT.MethodsThis is a secondary analysis of the patients with intracranial bleedings from the prospective multicenter emergency department-based RADOA registry, which collected data on patients admitted with major bleeding while taking VKA or DOAC. The primary endpoint was in-hospital mortality until day 30. We evaluated hematoma volume and short-term clinical outcomes in relation to the extent of active OAT according to coagulation parameters and OAT plasma levels measured by UPLC-MS/MS.ResultsOf 193 patients with major bleeding, 109 (56.5%) had intracranial hemorrhage [52.3% intracerebral (ICH), 33.9% subdural (SDH), 11.0% subarachnoidal (SAH)]. 64 (58.7%) were on VKA and 45 (41.2%) were on DOAC. On admission, we could confirm active anticoagulation in 97.7% of VKA-treated patients based on either INR > 1.3 or phenprocoumon levels and in 75.8% of DOAC-treated patients based on DOAC levels. Patients suffering an intracranial hemorrhage under VKA showed significantly larger hematoma volumes and a higher in-hospital mortality. Especially in intracerebral hemorrhage, we observed a higher initial severity and numerically greater proportion of early changes towards palliative therapy under VKA, which coincided with a numerically higher case fatality.ConclusionsWe show significantly smaller hematoma volumes for ICH and SDH under DOAC in comparison to VKA and a significantly lower 30-day in-hospital mortality rate of DOAC-ICH, even before the introduction of specific antidotes. These data strongly support the use of DOAC whenever possible in patients requiring OAT.Trial registrationhttp://www.Clinicaltrialsgov ; Unique identifier: NCT01722786.

Project description:ObjectivesTo determine the real world safety of dabigatran or rivaroxaban compared with warfarin in terms of gastrointestinal bleeding.DesignRetrospective cohort study.SettingLarge administrative database of commercially insured people in United States from 1 October 2010 through 31 March 2012.ParticipantsEnrollees with a prescription of warfarin, dabigatran, or rivaroxaban between 1 October 2010 and 31 March 2012, who were aged 18 years or older, had continuous enrollment and no oral anticoagulant use during the six months before the entry date, with known age and sex, and with no gastrointestinal bleeding for at least six months before the cohort entry date. The final study sample of 46,163 patients included 4907 using dabigatran, 1649 using rivaroxaban, and 39,607 using warfarin.Main outcome measureTime to gastrointestinal bleeding. Hazard ratios were derived from Cox proportional hazard models with propensity score weighting and robust estimates of errors.ResultsDabigatran users tended to be older (dabigatran v rivaroxaban v warfarin: 62.0 v 57.6 v 57.4 years) and more likely to be male (69% v 49% v 53%). The rate of gastrointestinal bleeding was highest among dabigatran users and lowest among rivaroxaban users (dabigatran v rivaroxaban v warfarin: 9.01 v 3.41 v 7.02 cases per 100 person years). After adjustment for potentially confounding covariates, there was no evidence of a statistically significant difference in the risk of gastrointestinal bleeding between dabigatran and warfarin users (adjusted hazard ratio 1.21, 95% confidence interval 0.96 to 1.53) or between rivaroxaban and warfarin users (0.98, 0.36 to 2.69).ConclusionsAlthough rates of gastrointestinal bleeding seem to be similar in this commercially insured sample of adults in the United States, we cannot rule out as much as a 50% increase in the risk of gastrointestinal bleeding with dabigatran compared with warfarin or a more than twofold higher risk of bleeding with rivaroxaban compared with warfarin.

Project description:Objectives: The purpose of our study is to investigate the effects of apolipoprotein B (APOB) and APOE gene polymorphisms on bleeding complications in patients receiving direct oral anticoagulants (DOACs). Methods: A total of 16 single nucleotide polymorphisms (SNPs) in 468 patients were genotyped. Six SNPs of ABCB1 (rs3842, rs1045642, rs2032582, rs1128503, rs3213619, and rs3747802), one SNP of CYP3A5 (rs776746), seven SNPs of APOB (rs1042034, rs2163204, rs693, rs679899, rs13306194, rs13306198, and rs1367117), and two SNPs of APOE (rs429358 and rs7412) were analyzed by a TaqMan genotyping assay. Multivariable logistic regression analysis with selected variables was performed for the construction of a risk scoring system. Two risk scoring systems were compared (demographic factors only vs. demographic factors and genetic factors). Results: In the multivariable analyses, two models were constructed; only demographic factors were included in Model I and both demographic factors and genetic factors in Model II. Rivaroxaban and anemia showed significant association with bleeding in both models. Additionally, ABCB1 rs3842 variant homozygote carriers (CC) and APOB rs13306198 variant allele carriers (AG, AA) had a higher risk of bleeding risk compared with that of wild-type allele carriers (TT, TC) and wild-type homozygote carriers (GG), respectively. Whereas the area under the receiver operating characteristic curve (AUROC) value using demographic factors only was 0.65 (95% confidence interval (CI): 0.56-0.74), the AUROC increased to 0.72 by adding genetic factors (95% CI: 0.65-0.80). The predicted bleeding risks of bleeding in patients with 0, 1, 2, 3, 4, 5, 6, 7 and 8 points from the logistic regression curve were 0.8%, 2.0%, 5.4%, 5.2%, 12.5%, 26.9%, 47.0%, 64.3% and 82.3%, respectively. Conclusions: The study results can be used for enhancing individualized treatment strategies in patients taking DOACs, helping clinicians predict the bleeding risk.

Project description:BackgroundClinical trials suggest lower rates of major bleeding with direct-acting oral anticoagulants (DOACs) than with warfarin, but anticoagulant-related bleeding remains one of the most common outpatient adverse drug events.MethodsWe estimated the number of emergency department (ED) visits and subsequent hospitalizations for oral anticoagulant-related bleeding in 2016-2020 based on active surveillance in a nationally representative, size-stratified probability sample of 60 U.S. hospitals. We estimated rates of ED visits using a nationally-projected retail prescription dispensing database.ResultsBased on 19,557 cases, oral anticoagulant-related bleeding resulted in an estimated 1,270,259 (95 % Confidence Interval [CI], 644,686-1,895,832) ED visits for the five years 2016-2020, of which 47.8 % (95 % CI, 40.6 %-55.0 %) resulted in hospitalization. Oral anticoagulant-related bleeding resulted in an estimated 230,163 (95% CI, 109,598-350,728) ED visits in 2016 and 301,433 (95% CI, 138,363-464,503) in 2020. During 2016-2020, ED visits for DOAC-related bleeding increased by an average of 27.9 % (95 % CI, 24.0 %-32.0 %; p < .001) per year, while ED visits for warfarin-related bleeding decreased by an average of 8.8 % (95 % CI, -10.7 % to -7.0 %; p = .001) per year. The estimated rate of bleeding visits per 100 patients dispensed oral anticoagulants at least once in 2016-2020 was highest for patients aged ≥ 80 years (13.1; 95 % CI, 6.2-20.0) and lowest for those aged <45 years (4.0; 95 % CI, 2.6-5.5); it was 5.9 visits per 100 patients dispensed DOACs [95 % CI, 2.5-9.2] and 13.0 visits per 100 patients dispensed warfarin [95 % CI, 7.4-18.7].ConclusionsAlthough the rates of ED visits for anticoagulant-related bleeding may be lower for DOACs than for warfarin, persistently large numbers of patients requiring ED visits for anticoagulant-related bleeding despite increased use of DOACs and declining use of warfarin suggest that efforts to improve appropriate prescribing and monitoring of anticoagulants remain important.

Dataset Information

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study.

Background

Methods

Results

Interpretation

Publications

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study.

Similar Datasets

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