Evaluation of bleeding in patients receiving direct oral anticoagulants.
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ABSTRACT:
SUBMITTER: Hellenbart EL
PROVIDER: S-EPMC5574591 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Publications
Evaluation of bleeding in patients receiving direct oral anticoagulants.
Hellenbart Erika L EL Faulkenberg Kathleen D KD Finks Shannon W SW
Vascular health and risk management 20170823
Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major ...[more]
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Project description:ObjectiveThe effect of direct oral anticoagulants (DOACs) on the risk of bleeding after tooth extraction remains unclear. This study aimed to evaluate the incidence of postextraction bleeding among patients who received DOAC and vitamin K antagonists (VKAs), such as warfarin.DesignThis study was a retrospective cohort analysis. Incidence rates and propensity score-matched regression models were used to compare the risks of bleeding after tooth extractions involving DOACs and VKAs.SettingThe study took place in a single university hospital in Japan.ParticipantsBetween April 2013 and April 2015, 543 patients underwent a total of 1196 simple tooth extractions.Primary outcome measureThe primary outcome measure was the occurrence of postextraction bleeding, which was defined as bleeding that could not be stopped by biting down on gauze and required medical treatment between 30?min and 7 days after the extraction.ResultsA total of 1196 tooth extractions (634 procedures) in 541 patients fulfilled the study criteria, with 72 extractions (41 procedures) involving DOACs, 100 extractions (50 procedures) involving VKAs and 1024 extractions (543 procedures) involving no anticoagulants. The incidences of postextraction bleeding per tooth for the DOAC, VKA and no anticoagulant extractions were 10.4%, 12.0% and 0.9%, respectively. The incidences of postextraction bleeding per procedure for DOACs, VKAs and no anticoagulants were 9.7%, 10.0% and 1.1%, respectively. In comparison to the VKA extractions, the DOAC extractions did not significantly increase the risk of postextraction bleeding (OR 0.69, 95% CIs 0.24 to 1.97; p=0.49).ConclusionsThe risk of postextraction bleeding was similar for DOAC and VKA extractions.
| S-EPMC5629650 | biostudies-literature
Project description:Polypharmacy is common in patients with atrial fibrillation (AF), making these patients vulnerable to the occurrence of potential drug-drug interactions (DDIs). We assessed the risk of ischemic stroke and major bleeding in the context of concomitant treatment with potential DDIs in patients with AF prescribed direct oral anticoagulants (DOACs). Using the common data model (CDM) based on an electronic health record (EHR) database, we included new users of DOACs from among patients treated for AF between January 2014 and December 2017 (n = 1938). The median age was 72 years, and 61.8% of the patients were males, with 28.2% of the patients having a CHA2DS2-VASc score in category 0-1, 49.4% in category 2-3, and 22.4% in category ≥ 4. The CHA2DS2-VASc score was significantly associated with ischemic stroke occurrence and hospitalization for major bleeding. Multiple logistic regression analysis showed that increased risk of ischemic stroke and hospitalization for major bleeding was associated with the number of DDIs regardless of comorbidities: ≥ 2 DDIs was associated with ischemic stroke (OR = 18.68; 95% CI, 6.22-55.27, P < 0.001) and hospitalization for major bleeding (OR = 5.01; 95% CI, 1.11-16.62, P < 0.001). DDIs can cause reduced antithrombotic efficacy or increased risk of bleeding in AF patients prescribed DOACs.
| S-EPMC8599657 | biostudies-literature
Project description:Direct oral anticoagulants are at least as effective as vitamin K antagonists for the prevention and treatment of thromboembolism. Unfortunately, differently from vitamin K antagonists, they have the great drawback of lacking specific antidotes in the case of bleeding or emergency situations such as trauma, stroke requiring thrombolysis, and urgent surgery. The progressive development of antidotes for these new drugs, which, it is hoped, will become available in the near future, will allow better and safer management of the rapid reversal of their anticoagulant effect.
| S-EPMC5016308 | biostudies-other
Project description:Essentials Currently, DOACs are given at fixed doses and do not require laboratory monitoring. Direct oral anticoagulant-specific measurements were performed at trough and peak. Patients who developed bleeding events showed higher DOAC plasma levels at peak. This study suggests the need of a more accurate DOAC dose assessment.BackgroundDirect oral anticoagulants (DOACs) are administered at fixed dose. The aim of the study was to evaluate the relationship between DOAC C-trough or C-peak plasma levels and bleeding complications in patients with non-valvular atrial fibrillation (NVAF).MethodsFive hundred sixty five consecutive naive NVAF patients were enrolled. The DOAC measurements at C-trough and at C-peak (available in 411 patients) were performed at steady state, within the first month of treatment. Major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and minor bleeding (MinB), occurring during 1 year of follow-up after blood sampling, were recorded. For each DOAC, interval of C-trough and C-peak levels was subdivided into four equal classes and results were attributed to these classes; the median values of results were also calculated.ResultsTwo hundred eight patients were on apixaban, 185 on dabigatran, and 172 on rivaroxaban. For 1-[qqqdeletezzz] year follow up for all patients, we observed: 19 MB (3.36%), 6 CRNMB (1.06%), and 47 MinB (8.31%). The prevalence of bleeding patients with anticoagulant levels in the upper classes of C-peak activity (II + III + IV) was higher than that in the lowest class. Normalized results of C-peak levels were higher in patients with bleeding than in those without bleeding.ConclusionsBleeding complications during DOAC treatment were more frequent among atrial fibrillation (AF) patients with higher C-peak anticoagulant levels. In addition to a previous study that showed an increased risk of thrombotic complications in the patients with low C-trough levels, this study seems to indicate that patients with NVAF on DOACs would need a more accurate definition of their optimal therapeutic window.
| S-EPMC6852698 | biostudies-literature
Project description:BACKGROUND:We evaluated adherence to dosing criteria for patients with atrial fibrillation (AF) taking dabigatran or rivaroxaban and the impact of off-label dosing on thromboembolic and bleeding risk. METHODS:We used data for a retrospective cohort from a large U.S. health plan for Medicare beneficiaries age?>?=65?years with AF who initiated dabigatran or rivaroxaban during 2010-2016. Stroke and major bleeding were quantified in patients who were eligible for low dose but received standard dose, and in patients who were eligible for standard dose but received low dose. RESULTS:We identified 8035 and 19,712 patients who initiated dabigatran or rivaroxaban, respectively. Overall, 1401 (17.4%) and 7820 (39.7%) patients who received dabigatran and rivaroxaban met criteria for low dose, respectively. Of those, 959 (68.5%) and 3904 (49.9%) received standard dose. In contrast, 1013 (15.3%) and 2551 (21.5%) of patients eligible for standard dose dabigatran and rivaroxaban received low dose. Mean follow-up for patients eligible for low and standard dose dabigatran and rivaroxaban were 13.9, 15.1, 10.1, and 12.3?months, respectively. In unadjusted analyses, patients eligible for low or standard dose dabigatran and rivaroxaban but receiving off-label dose, had no differences in the rates of ischemic stroke. Among patients who met criteria for standard dose direct oral anticoagulants (DOAC), use of low dose was associated with significantly higher risk of any major bleeding (Dabigatran: HR?=?1.44; 95% CI 1.14-1.8, P?=?0.002, Rivaroxaban HR 1.34, 95% CI 1.11-1.6, P?=?0.002) and gastrointestinal bleeding (Dabigatran: HR?=?1.48; 95% CI 1.08-2, P?=?0.016). In patients who met criteria for low dose DOACs, there was lower risk of major bleeding (Dabigatran: HR?=?0.59; 95% CI 0.43-0.8, P?<?0.001), gastrointestinal (Rivaroxaban: HR 0.79; 95% CI 0.64-0.98, P?=?0.03) and intracranial bleeding (Dabigatran: HR?=?0.33; 95% CI 0.12-0.9, P?=?0.001) with standard dosing. After propensity matching, use of off-label doses was not associated with stroke, major, gastrointestinal or intracranial bleeding for either dabigatran or rivaroxaban. CONCLUSIONS:While a significant number of patients receive higher or lower dose of dabigatran and rivaroxaban than recommended, we found no evidence of significant impact on thromboembolic or hemorrhagic outcomes.
| S-EPMC6998084 | biostudies-literature
Project description:AimsDrug exposure status based on routinely collected data might be misclassified when the database contains only prescriptions from 1 type of prescriber (e.g. general practitioner and not specialist). This study aims to quantify the impact of such exposure misclassification on the risk of major bleeding and stroke/transient ischaemic attack (TIA)associated with direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs).MethodsIncident anticoagulant users (>12 mo free of anticoagulation use) in the Dutch PHARMO Database Network between 2008 and 2017 were included. Drug exposure was assessed using pharmacy dispensing information. The risks of hospital admission of major bleeding for DOAC vs. VKA users was assessed with Cox regression analysis, where exposure was based on all dispensings, on general practitioner (GP)-prescribed dispensings only or on specialist-prescribed dispensings only. Hazard ratios (HRs) were estimated also for hospitalization for gastrointestinal bleeding, intracranial bleeding and stroke/TIA.ResultsWe included 99 182 VKA-initiators and 21 795 DOAC-initiators. Use of DOAC was associated with a lower risk of major bleeding compared to VKA use; HR 0.79 (95% confidence interval 0.70-0.90), 0.78 (0.68-0.91) and 0.62 (0.50-0.76), for exposure based on complete dispensing information, only GP- and only specialist-prescribed dispensings, respectively. Similar results were found for the other bleeding outcomes. For stroke/TIA the HRs were 0.96 (0.84-1.09), 1.00 (0.84-1.18) and 0.72 (0.58-0.90), respectively.ConclusionIncluding only GP-prescribed anticoagulant dispensings in this case did not materially impact the effect estimates compared to including all anticoagulant dispensings. Including only specialist-prescribed dispensings, however, strengthened the effect estimates.
| S-EPMC8451929 | biostudies-literature
Project description:BACKGROUND:No scores presently exist to predict bleeding in atrial fibrillation (AF) populations using direct oral anticoagulants (DOACs). We used data from two independent healthcare claims databases to develop and validate a predictive model of major bleeding in a contemporary AF population. METHODS:Patients with non-valvular AF initiating oral anticoagulation were identified in the MarketScan databases from 2007-2014. Using Cox regression models in 1000 bootstrapped samples, we developed a model that selected variables predicting major bleeding in the first year after anticoagulant initiation. The final model was validated in patients with non-valvular AF in the Optum Clinformatics database in the period 2009-2015. The discriminative ability of existing bleeding scores were individually evaluated and compared with the new bleeding model termed Anticoagulation-specific Bleeding Score (ABS) in both MarketScan and Optum. RESULTS:Among 119,083 patients with AF initiating oral anticoagulation in the derivation cohort, 4,030 experienced a bleeding event. The variable selection model identified 15 variables (including individual type of oral anticoagulant) associated with major bleeding. Discrimination of the model was modest [c-statistic 0.68, 95% confidence interval (CI) 0.67-0.69]. The model was subsequently applied to 81,285 AF patients in the validation data set (3,238 bleeding events), showing similar discrimination (c-statistic 0.68, 95% CI 0.67-0.69). In both cohorts, the predictive performance of the ABS was better than the existing models for bleeding prediction in AF. CONCLUSIONS:We developed a model that uses administrative healthcare data for the identification of AF patients at higher risk of bleeding after initiation of oral anticoagulation, taking into account the lower bleeding risk in DOAC compared to warfarin users.
| S-EPMC6130859 | biostudies-literature
Project description:Direct oral anticoagulants (DOACs) have been licensed worldwide for several years for various indications. Each year, 10-15% of patients on oral anticoagulants will undergo an invasive procedure and expert groups have issued several guidelines on perioperative management in such situations. The perioperative guidelines have undergone numerous updates as clinical experience of emergency management has increased and perioperative studies including measurement of residual anticoagulant levels have been published. The high inter-patient variability of DOAC plasma levels has challenged the traditional recommendation that perioperative DOAC interruption should be based only on the elimination half-life of DOACs, especially before invasive procedures carrying a high risk of bleeding. Furthermore, recent publications have highlighted the potential danger of heparin bridging use when DOACs are stopped before an invasive procedure. As antidotes are progressively becoming available to manage severe bleeding or urgent procedures in patients on DOACs, accurate laboratory tests have become the standard to guide their administration and their actions need to be well understood by clinicians. This review aims to provide a systematic approach to managing patients on DOACs, based on recent updates of various perioperative guidance, and highlighting the advantages and limits of recommendations based on pharmacokinetic properties and laboratory tests.
| S-EPMC5433145 | biostudies-literature
Project description:Vitamin K antagonists have been used for many years as the treatment of choice for long-term oral anticoagulation in patients with non-valvular atrial fibrillation. Unfortunately, the use of those drugs in the real-world setting, particularly among elderly patients, is suboptimal because of their limitations in management. Therefore, many patients were not adequately anticoagulated. Direct oral anticoagulants have been demonstrated to overcome almost all the limitations derived from the use of vitamin K antagonists. Direct oral anticoagulants are at least as effective as vitamin K antagonists in preventing thromboembolic events in patients with non-valvular atrial fibrillation and safer in reducing the risk of intracranial haemorrhage and all-cause mortality. However, as a result of the strict inclusion and exclusion criteria applied to patients, data coming from randomized controlled trials might not apply to the general population. Furthermore, elderly patients were scarcely represented in randomized controlled trials with direct oral anticoagulants. Therefore in elderly patients with non-valvular atrial fibrillation, unmet clinical needs still exist. This review article highlights some of them and provides potential answers based on the results coming from randomized clinical trials, real-world data, and the authors' clinical experience.
| S-EPMC8189975 | biostudies-literature
Project description:IntroductionPostmarketing pharmacovigilance reports have raised concerns about non-bleeding adverse events associated with direct oral anticoagulants (DOACs), but only limited results are available from large claims databases.ObjectiveThe aim of this study was to assess the potential association between DOAC initiation and the onset of four types of non-bleeding adverse events by sequence symmetry analysis (SSA).MethodsSSA was performed using nationwide data from the French National Healthcare databases (Régime Général, 50 million beneficiaries) to assess a cohort of 386,081 DOAC new users for the first occurrence of four types of non-bleeding outcomes: renal, hepatic, skin outcomes identified by using hospitalization discharge diagnoses, and gastrointestinal outcomes by using medication reimbursement. Asymmetry in the distribution of each investigated outcome occurring before and after initiation of DOAC therapy was used to test the association between DOAC therapy and these outcomes. SSA inherently controls for time-constant confounders, and adjusted sequence ratios were computed after correcting for temporal trends. Negative (glaucoma) and positive (bleeding, depressive disorders) control outcomes were used and analyses were replicated on a cohort of 310,195 patients initiating a vitamin K antagonist (VKA).ResultsThis study demonstrated the expected positive association between either DOAC or VKA therapy and hospitalised bleeding and initiation of antidepressant therapy, while no association was observed between either DOAC or VKA therapy and initiation of antiglaucoma medications. For DOAC therapy, signals were the associations with hepatic outcomes, including acute liver injury [for the 3-month time window, aSR3?=?2.71, 95% confidence interval (CI) 1.79-4.52]; gastrointestinal outcomes, including initiation of drugs for constipation and antiemetic drugs (aSR3?=?1.31, 95% CI 1.27-1.36; and 1.17, 95% CI 1.12-1.22, respectively); and kidney diseases (aSR3?=?1.33, 95% CI 1.29-1.37).ConclusionResults of this nationwide study suggest that DOACs are associated with rare but severe liver injury and more frequent gastrointestinal disorders. A low risk of kidney injury with DOAC therapy can also not be excluded.
| S-EPMC6061378 | biostudies-literature