Delayed Intracranial Hemorrhage after Blunt Head Trauma while on Direct Oral Anticoagulant: Systematic Review and Meta-Analysis.
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SUBMITTER: Puzio TJ
PROVIDER: S-EPMC8722268 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-? and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.
| S-EPMC6057345 | biostudies-literature
Project description:ImportanceDirect oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.ObjectiveTo evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.Data sourcesPubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.Study selectionThe eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.Data extraction and synthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.Main outcomes and measuresThe primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.ResultsA total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.Conclusions and relevanceIn the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.
| S-EPMC9636520 | biostudies-literature
Project description:STUDY OBJECTIVE:We determine the prevalence of significant intracranial injury among adults with blunt head trauma who are receiving preinjury anticoagulant or antiplatelet medications. METHODS:This was a multicenter, prospective, observational study conducted from December 2007 to December 2015. Patients were enrolled in 3 emergency departments (EDs) in the United States. Adults with blunt head trauma who underwent neuroimaging in the ED were included. Use of preinjury aspirin, clopidogrel, and warfarin was recorded. Data on direct oral anticoagulants were not specifically recorded. The primary outcome was prevalence of significant intracranial injury on neuroimaging. The secondary outcome was receipt of neurosurgical intervention. RESULTS:Among 9,070 patients enrolled in this study, the median age was 53.8 years (interquartile range 34.7 to 74.3 years) and 60.7% were men. A total of 1,323 patients (14.6%) were receiving antiplatelet medications or warfarin, including 635 receiving aspirin alone, 109 clopidogrel alone, and 406 warfarin alone. Compared with that of patients without any coagulopathy, the relative risk of significant intracranial injury was 1.29 (95% confidence interval [CI] 0.88 to 1.87) for patients receiving aspirin alone, 0.75 (95% CI 0.24 to 2.30) for those receiving clopidogrel alone, and 1.88 (95% CI 1.28 to 2.75) for those receiving warfarin alone. The relative risk of significant intracranial injury was 2.88 (95% CI 1.53 to 5.42) for patients receiving aspirin and clopidogrel in combination. CONCLUSION:Patients receiving preinjury warfarin or a combination of aspirin and clopidogrel were at increased risk for significant intracranial injury, but not those receiving aspirin alone. Clinicians should have a low threshold for neuroimaging when evaluating patients receiving warfarin or a combination of aspirin and clopidogrel.
| S-EPMC7039766 | biostudies-literature
Project description:Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients.
| S-EPMC10249073 | biostudies-literature
Project description:The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism.We searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes.Eight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25-0.45; Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58-1.77; Q=24.68, P for heterogeneity <0.001). No significant publication bias was detected in our analyses.In observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk-benefit profile of anticoagulation resumption after ICH.
| S-EPMC5699447 | biostudies-literature
Project description:Direct oral anticoagulants (DOACs) are increasingly prescribed in treatment of cancer-associated thrombosis, but limited data exist regarding safety of DOACs in patients with brain metastases. We aimed to determine the incidence of intracranial hemorrhage (ICH) in patients with brain metastases receiving DOACs or low-molecular-weight heparin (LMWH) for venous thromboembolism or atrial fibrillation. An international 2-center retrospective cohort study was designed. Follow-up started on the first day of concomitant anticoagulation and brain tumor diagnosis. At least 2 brain imaging studies were mandated. The primary outcome was the cumulative incidence of any spontaneous ICH at 12-month follow-up with death as a competing risk. Major ICH was defined as spontaneous, ≥10 mL in volume, symptomatic, or requiring surgical intervention. Imaging studies were centrally reviewed by a neuroradiologist blinded for anticoagulant type. PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke) score for prediction of ICH was calculated. We included 96 patients with brain metastases (41 DOAC, 55 LMWH). The 12-month cumulative incidence of major ICH was 5.1% in DOAC-treated patients and 11.1% in those treated with LMWH (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.09-2.21). When anticoagulation was analyzed as a time-varying covariate, the risk of any ICH did not differ between DOAC- and LMWH-treated patients (HR, 0.98; 95% CI, 0.28-3.40). PANWARDS score was not associated with ICH risk. This international 2-center study suggests comparable safety of LMWH and DOACs in patients with brain metastases.
| S-EPMC7756985 | biostudies-literature
Project description: Not available
| S-EPMC11210085 | biostudies-literature
Project description:ImportanceNon-vitamin K antagonist oral anticoagulants (NOACs) might be an attractive choice for stroke prevention in people without atrial fibrillation who may harbor a potential source of cardiac emboli, but not if certain individual NOACs carry risks of intracranial hemorrhage that are heightened relative to aspirin.ObjectiveTo conduct a systematic review and meta-analysis of randomized clinical trials to assess the risk of intracranial hemorrhage with individual NOACs vs aspirin across all indications.Data sourcesWe searched PubMed, Embase, CENTRAL, and ClinicalTrials.gov from inception to May 28, 2018, with the terms novel oral anticoagulants, non-vitamin K antagonist oral anticoagulants, direct oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, warfarin, Coumadin, vitamin K antagonist, aspirin, acetylsalicylic acid, or ASA, and major bleeding, fatal bleeding, or intracranial hemorrhage. We restricted our search to clinical trials on humans. There were no language restrictions.Study selectionRandomized clinical trials of 3 months or longer that included a comparison of the outcomes of NOAC use vs use of aspirin.Data extraction and synthesisTwo investigators independently abstracted data from eligible studies. We computed a fixed-effect estimate based on the Mantel-Haenszel method.Main outcomes and measuresOdds ratios (ORs) with 95% CI were used as a measure of the association of individual NOAC vs aspirin with the risk of intracranial hemorrhage. The hypothesis that intracranial hemorrhage risk would be higher with NOACs than aspirin was formulated during data collection.ResultsOur principal analysis included 5 randomized clinical trials comparing 1 or more NOACs with aspirin, with 39 398 individuals enrolled. Pooling the results from the fixed-effects model showed that a dose of 15 to 20 mg of rivaroxaban once daily was associated with an increased risk of intracranial hemorrhage (2 trials; OR, 3.31 [95% CI, 1.42 to 7.72]) compared with aspirin, while a 10-mg dose of rivaroxaban once daily or a 5-mg dose twice daily (3 trials; OR, 1.43 [95% CI, 0.93 to 2.21]) and a 5-mg dose of apixaban twice daily (1 trial; OR, 0.84 [95% CI, 0.38 to 1.88]) were not.Conclusions and relevanceA 15-mg to 20-mg dose of rivaroxaban once daily is associated with substantially increased risks of intracranial hemorrhage, while smaller daily doses of rivaroxaban and apixaban were not, implying that risk increase is dose dependent. It may be worthwhile to conduct randomized clinical trials comparing specific NOACs in specific doses (eg, apixaban, 5 mg twice daily) and aspirin in patients without atrial fibrillation, but with potential sources of cardiac emboli that could cause stroke.
| S-EPMC6583193 | biostudies-literature
Project description:BackgroundExtrapolation of clinical trial results comparing warfarin and direct-acting oral anticoagulant (DOAC) users experiencing major hemorrhage to clinical care is challenging due to differences seen among non-randomized oral anticoagulant users, bleed location, and etiology. We hypothesized that inpatient all-cause-mortality among patients presenting with major hemorrhage differed based on the home-administered anticoagulant medication class, DOAC versus warfarin.MethodsMore than 1.5 million hospitalizations were screened and 3731 patients with major hemorrhage were identified in the REDS-III Recipient Database. Propensity score matching and stratification were used to account for potentially confounding factors.ResultsInpatient all-cause-mortality was lower for DOAC (HR = 0.60, 95%CI 0.45-0.80, p = 0.0005) before accounting for confounding and competing events. Inpatient all-cause-mortality for 1266 propensity-score-matched patients compared using proportional hazards regression did not differ (HR = 0.84, 95%CI 0.58-1.22, p = 0.36). Inpatient all-cause-mortality in stratified analyses (warfarin as reference) produced: HR = 0.69 (95%CI 0.31-1.55) for traumatic head injuries; HR = 1.10 (95%CI 0.62-1.95) for non-traumatic head injuries; HR = 0.62 (95%CI 0.20-1.94) for traumatic, non-head injuries; and HR = 0.69 (95%CI 0.29-1.63) for non-traumatic, non-head injuries. Mean time to discharge was shorter for DOAC (HR = 1.17, 95%CI 1.05-1.30, p = 0.0034) in the propensity score matched analysis. Plasma transfusion occurred in 42% of warfarin hospitalizations and 11% of DOAC hospitalizations. Vitamin K was administered in 63% of warfarin hospitalizations.ConclusionsAfter accounting for differences in patient characteristics, location of bleed, and traumatic injury, inpatient survival was no different in patients presenting with major hemorrhage while on DOAC or warfarin.
| S-EPMC7035631 | biostudies-literature
Project description:Venous thromboembolism (VTE) and atrial fibrillation (AF) is a major burden on the health care system. The average occurrence of venous thromboembolism annually is around 108 per 100,000 person-year. DOACs have transformed treatment of coagulation disorder, and now, it is the leading treatment for stroke prevention in AF and VTE prophylaxis and treatment. For more many years, oral vitamin K antagonists (VKAs) were the drug of choice in managing VTE. VKAs treatment is safe and effective if therapeutic international normalized ratio (INR) maintained on the target. However, achieving a stable, therapeutic international normalized ratio (INR) can be difficult and challenging in the context of drug and food interactions and liver disorder, resulting in undertreatment which increases the risk of thromboembolism or overtreatment which might cause bleeding. Herein, we provide an overview of DOACs indications, use in specific comorbidities, monitoring parameters, perioperative management, and reversal agents.
| S-EPMC9638657 | biostudies-literature