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JAMA Network Open Aug 2023Extending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear...
IMPORTANCE
Extending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear whether clinical outcomes differ when using direct oral anticoagulants (DOACs) or warfarin.
OBJECTIVE
To compare rates of recurrent VTE, hospitalizations for hemorrhage, and all-cause death among adults prescribed DOACs or warfarin whose anticoagulant treatment was extended beyond 6 months after acute VTE.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was conducted in 2 integrated health care delivery systems in California with adults aged 18 years or older who received a diagnosis of incident VTE between 2010 and 2018 and completed at least 6 months of oral anticoagulant treatment with DOACs or warfarin. Patients were followed from the end of the initial 6-month treatment period until discontinuation of anticoagulation, occurrence of an outcome event, health plan disenrollment, or end of the study follow-up period (December 31, 2019). Data were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Data analysis was conducted from March 2022 to January 2023.
EXPOSURE
Dispensed prescriptions of DOACs or warfarin after a 6-month initial treatment for VTE.
MAIN OUTCOMES AND MEASURES
The primary outcomes were rates per 100 person-years of recurrent VTE, hospitalizations for hemorrhage, and all-cause death. Comparison of DOAC and warfarin outcomes were performed using multivariable Cox proportional hazards regression.
RESULTS
A total of 18 495 patients (5477 [29.6%] aged ≥75 years; 8973 women [48.5%]) with VTE who were treated with at least 6 months of anticoagulation were identified, of whom 2134 (11.5%) were receiving DOAC therapy and 16 361 (88.5%) were receiving warfarin therapy. Unadjusted event rates were lower for patients receiving DOAC therapy than warfarin therapy for recurrent VTE (event rate per 100 person-years, 2.92 [95% CI, 2.29-3.54] vs 4.14 [95% CI, 3.90-4.38]), hospitalizations for hemorrhage (event rate per 100 person-years, 1.02 [95% CI, 0.66-1.39] vs 1.81 [95% CI, 1.66-1.97]), and all-cause death (event rate per 100 person-years, 3.79 [95% CI, 3.09-4.49] vs 5.40 [95% CI, 5.13-5.66]). After multivariable adjustment, DOAC treatment was associated with a lower risk of recurrent VTE (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.52-0.82). For patients prescribed DOAC treatment, the risks of hospitalization for hemorrhage (aHR, 0.79; 95% CI, 0.54-1.17) and all-cause death (aHR, 0.96; 95% CI, 0.78-1.19) were not significantly different than those for patients prescribed warfarin treatment.
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with VTE who continued warfarin or DOAC anticoagulation beyond 6 months, DOAC treatment was associated with a lower risk of recurrent VTE, supporting the use of DOACs for the extended treatment of VTE in terms of clinical outcomes.
Topics: Adult; Humans; Female; Warfarin; Venous Thromboembolism; Cohort Studies; Anticoagulants; Hemorrhage
PubMed: 37581888
DOI: 10.1001/jamanetworkopen.2023.28033 -
Journal of Medical Internet Research Jul 2023Oral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented to support it.
OBJECTIVE
The aim of the study is to systematically review the evidence on the impact of telemedicine-based oral anticoagulation management compared to usual care on thromboembolic and bleeding events.
METHODS
Randomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection and data extraction. Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models.
RESULTS
In total, 25 randomized controlled trials were included (n=25,746 patients) and classified as moderate to high risk of bias by the Cochrane tool. Telemedicine resulted in lower rates of thromboembolic events, though not statistically significant (n=13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07; I=42%), comparable rates of major bleeding (n=11 studies, RR 0.94, 95% CI 0.82-1.07; I=0%) and mortality (n=12 studies, RR 0.96, 95% CI 0.78-1.20; I=11%), and an improved time in therapeutic range (n=16 studies, mean difference 3.38, 95% CI 1.12-5.65; I=90%). In the subgroup of the multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48).
CONCLUSIONS
Telemedicine-based oral anticoagulation management resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events, and better anticoagulation quality compared to standard care. Given the potential benefits of telemedicine-based care, such as greater access to remote populations or people with ambulatory restrictions, these findings may encourage further implementation of eHealth strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases. Meanwhile, researchers should develop higher-quality evidence focusing on hard clinical outcomes, cost-effectiveness, and quality of life.
TRIAL REGISTRATION
PROSPERO International Prospective Register of Systematic Reviews CRD42020159208; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=159208.
Topics: Humans; Anticoagulants; Quality of Life; Hemorrhage; Thromboembolism; Telemedicine
PubMed: 37428532
DOI: 10.2196/45922 -
Revista Da Associacao Medica Brasileira... 2023The aim of this study was to carry out a systematic review of the literature with meta-analysis to evaluate the effect of using oral contraceptive and hormone... (Meta-Analysis)
Meta-Analysis
Does the use of oral contraceptives or hormone replacement therapy offer protection against the formation or rupture of intracranial aneurysms in women?: a systematic review and meta-analysis.
OBJECTIVE
The aim of this study was to carry out a systematic review of the literature with meta-analysis to evaluate the effect of using oral contraceptive and hormone replacement therapy as a protective factor in the formation of intracranial aneurysms and subarachnoid hemorrhage.
METHODS
This is a systematic review of the literature with meta-analysis, using PubMed and Embase as databases and the PRISMA method. Case-control and cohort studies published until December 2022 were included in this review.
RESULTS
Four studies were included in this review; three of which were eligible for meta-analysis. Regarding the use of oral contraceptive and the development of subarachnoid hemorrhage, there was a lower risk of aneurysm rupture with an odds ratio 0.65 (confidence interval 0.5-0.85). In the analysis of patients using hormone replacement therapy and developing subarachnoid hemorrhage, there was also a lower risk of aneurysm rupture with an OR 0.54 (CI 0.39-0.74). Only one article analyzed the formation of intracranial aneurysm and the use of hormone replacement therapy and oral contraceptive, and there was a protective effect with the use of these medications. oral contraceptive: OR 2.1 (CI 1.2-3.8) and hormone replacement therapy: OR 3.1 (CI 1.5-6.2).
CONCLUSION
The use of hormone replacement therapy and oral contraceptive has a protective effect in intracranial aneurysm rupture and formation.
Topics: Humans; Female; Intracranial Aneurysm; Contraceptives, Oral; Subarachnoid Hemorrhage; Hormone Replacement Therapy; Cohort Studies; Risk Factors
PubMed: 37556637
DOI: 10.1590/1806-9282.2023S118 -
Stroke Dec 2023This focused update about antiplatelet agents to reduce the high risk of major adverse cardiovascular events after stroke due to spontaneous (nontraumatic) intracerebral... (Review)
Review
This focused update about antiplatelet agents to reduce the high risk of major adverse cardiovascular events after stroke due to spontaneous (nontraumatic) intracerebral hemorrhage (ICH) complements earlier updates about blood pressure-lowering, lipid-lowering, and oral anticoagulation or left atrial appendage occlusion for atrial fibrillation after ICH. When used for secondary prevention in people without ICH, antiplatelet agents reduce the risk of major adverse cardiovascular event (rate ratio, 0.81 [95% CI, 0.75-0.87]) and might increase the risk of ICH (rate ratio, 1.67 [95% CI, 0.97-2.90]). Before 2019, guidance for clinical decisions about antiplatelet agent use after ICH has focused on estimating patients' predicted absolute risks and severities of ischemic and hemorrhagic major adverse cardiovascular event and applying the known effects of these drugs in people without ICH to estimate whether individual ICH survivors in clinical practice might be helped or harmed by antiplatelet agents. In 2019, the main results of the RESTART (Restart or Stop Antithrombotics Randomized Trial) randomized controlled trial including 537 survivors of ICH associated with antithrombotic drug use showed, counterintuitively, that antiplatelet agents might not increase the risk of recurrent ICH compared to antiplatelet agent avoidance over 2 years of follow-up (12/268 [4%] versus 23/268 [9%]; adjusted hazard ratio, 0.51 [95% CI, 0.25-1.03]; =0.060). Guidelines in the United States, Canada, China, and the United Kingdom and Ireland have classified the level of evidence as B and indicated that antiplatelet agents may be considered/reasonable after ICH associated with antithrombotic agent use. Three subsequent clinical trials have recruited another 174 participants with ICH, but they will not be sufficient to determine the effects of antiplatelet therapy on all major adverse cardiovascular events reliably when pooled with RESTART. Therefore, ASPIRING (Antiplatelet Secondary Prevention International Randomized Study After Intracerebral Hemorrhage) aims to recruit 4148 ICH survivors to determine the effects of antiplatelet agents after ICH definitively overall and in subgroups.
Topics: Humans; Platelet Aggregation Inhibitors; Treatment Outcome; Cerebral Hemorrhage; Stroke; Fibrinolytic Agents; Anticoagulants
PubMed: 37916459
DOI: 10.1161/STROKEAHA.123.036886 -
Thrombosis Research Nov 2023The 2021 International Society on Thrombosis and Haemostasis' (ISTH) recommends standard doses of apixaban and rivaroxaban regardless of high body mass index (BMI) and...
BACKGROUND
The 2021 International Society on Thrombosis and Haemostasis' (ISTH) recommends standard doses of apixaban and rivaroxaban regardless of high body mass index (BMI) and weight, but had not compare DOACs head-to-head in obesity or address underweight patients.
METHODS
Our aim is to evaluate the safety and efficacy of DOACs in underweight and obese patients compared to warfarin. The primary endpoints include incidence of thromboembolic and bleeding events. Descriptive statistics was used for continuous variables. The Kruskal-Wallis test was used to compare the four-groups for continuous measures and the chi-square test or Fisher's exact test was used to analyze categorical data. The chi-square test or Fisher's exact test, was used for categorical variables, and the Mann-Whitney test (the non-parametric counterpart to the two-sample t-test) for continuous data.
RESULTS
Of 2940 patients receiving anticoagulation for venous thromboembolism (VTE) treatment or atrial fibrillation (AF), 492 met eligibility criteria. Within each group, 248 patients received warfarin, 101 received apixaban, 100 received rivaroxaban and 43 received dabigatran. Patients were characterized in 4 body mass index (BMI) categories, in which 80 were underweight and 412 were obese.
CONCLUSIONS
When each DOAC was compared to warfarin in rates of VTE, apixaban showed statistically significant lower rate of VTE (p = 0.0149). However, no statistical significance was identified in the rate of VTE between DOACs combined vs. warfarin (p = 0.1529). When each DOAC was compared to warfarin, apixaban showed the lowest rate of overall bleeding (p = 0.0194). However, no statistical difference in the rate of bleeding was observed between DOACs combined vs. warfarin (p = 0.3284). Patients with extreme body weights requiring anticoagulation for VTE and AF may safety benefit from DOAC therapy. This evaluation showed apixaban with the lowest rate of VTE and bleeding compared to warfarin, rivaroxaban, and dabigatran. These results provide experience for the clinician to use DOACs, particularly apixaban, in underweight and obese populations.
Topics: Humans; Warfarin; Rivaroxaban; Dabigatran; Venous Thromboembolism; Thinness; Anticoagulants; Hemorrhage; Atrial Fibrillation; Obesity; Pyridones; Administration, Oral
PubMed: 37738772
DOI: 10.1016/j.thromres.2023.09.001 -
Antioxidants & Redox Signaling Oct 2023Several aging-related pathophysiological mechanisms have been described to contribute to increased thrombotic risk in the elderly, including oxidative stress,...
Several aging-related pathophysiological mechanisms have been described to contribute to increased thrombotic risk in the elderly, including oxidative stress, endothelial dysfunction, and platelet and coagulation cascade activation. Antithrombotic treatment in the elderly should be individualized. Recent studies have clarified some pathophysiological mechanisms of enhanced oxidative stress and thrombotic alterations in older adults. In the last decade, randomized trials have evaluated different antithrombotic strategies to reduce the risk of cardiovascular events in these patients. The proportion of elderly patients included in clinical trials is generally low, thus not reflecting the daily clinical practice. There is no consensus on the most appropriate antithrombotic treatment in the elderly, also considering that bleeding risk management may be challenging in this high-risk subgroup of patients. Routine antiplatelet treatment is not a valid strategy for the primary prevention of cardiovascular events given the associated high risk of bleeding. In elderly patients with acute coronary syndrome, low-dose prasugrel or clopidogrel, shorter dual antiplatelet therapy, and no pretreatment before stent placement should be considered. Advanced age should not be the only reason for the underuse of oral anticoagulation in patients with atrial fibrillation, with direct oral anticoagulants preferred over warfarin for stroke prevention. Instead, a case-by-case clinical evaluation is warranted based on patient's bleeding risk also. There is a need for a structured tailored approach to manage thrombotic risk in elderly patients. The choice of the most appropriate antithrombotic treatment should balance efficacy and safety to reduce the risk of bleeding.
PubMed: 37742116
DOI: 10.1089/ars.2023.0373 -
Journal of Clinical Medicine Dec 2023Non-valvular atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) are two common diseases in elderly populations. Despite the effectiveness of oral... (Review)
Review
Non-valvular atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) are two common diseases in elderly populations. Despite the effectiveness of oral anticoagulant therapy in cardioembolic stroke prevention, intracranial hemorrhage represents the most serious complication of these therapies. Cerebral amyloid angiopathy is one of the main risk factors for spontaneous intracranial bleeding, and this risk is highly increased by age and concomitant antithrombotic therapies. Cerebral amyloid angiopathy can be silent for years and then manifest with clinical features simulating TIA (TIA-mimics) or stroke in AF patients, pushing clinicians to rapidly start VKAs or DOACs, thus increasing the risk of intracranial bleeding if the diagnosis of CAA was unknown. Because the cerebral amyloid angiopathy is easily diagnosed with non-contrast MRI, suspecting the disease can avoid catastrophic complications. In this review, we will provide physicians managing anticoagulant therapies with key tips to familiarize themselves with cerebral amyloid angiopathy, with a focus on the possible clinical presentations and on the diagnostic criteria.
PubMed: 38137773
DOI: 10.3390/jcm12247704 -
Annals of Emergency Medicine Sep 2023Direct oral anticoagulants (DOACs) are widely used for the prevention and treatment of venous thromboembolism and stroke. When emergency reversal of DOAC-related... (Review)
Review
Direct oral anticoagulants (DOACs) are widely used for the prevention and treatment of venous thromboembolism and stroke. When emergency reversal of DOAC-related anticoagulation is required, specific DOAC reversal agents are recommended, including idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. However, specific reversal agents are not always available, andexanet alfa has not been approved for urgent surgery, and clinicians need to know the patient's anticoagulant medication before administering these treatments. Four-factor prothrombin complex concentrates (4F-PCCs) are recognized as nonspecific, alternative hemostatic agents for treatment of DOAC-related bleeding. Evidence from preclinical and clinical studies shows that they may reduce the anticoagulant effects of DOACs and may help control DOAC-related bleeding. However, randomized controlled trials are lacking, and most data are from retrospective or single-arm prospective studies in bleeding associated with activated factor X inhibitors. There are no clinical data showing the efficacy of 4F-PCC for the treatment of bleeding in dabigatran-treated patients. This review focuses on the current evidence of 4F-PCC use in controlling bleeding associated with DOACs and provides an expert opinion on the relevance of these data for clinical practice. The current treatment landscape, unmet needs, and future directions are also discussed.
Topics: Humans; Dabigatran; Clinical Relevance; Retrospective Studies; Prospective Studies; Anticoagulants; Hemorrhage; Administration, Oral; Recombinant Proteins
PubMed: 37204347
DOI: 10.1016/j.annemergmed.2023.04.015 -
Translational Stroke Research Nov 2023Risk of hemorrhage remains with antiplatelet medications required with carotid stenting during endovascular therapy (EVT) for tandem lesion (TLs). We evaluated the...
Risk of hemorrhage remains with antiplatelet medications required with carotid stenting during endovascular therapy (EVT) for tandem lesion (TLs). We evaluated the safety of antiplatelet regimens in EVT of TLs. This multicenter study included anterior circulation TL patients from 2015 to 2020, stratified by periprocedural EVT antiplatelet strategy: (1) no antiplatelets, (2) single oral, (3) dual oral, and (4) intravenous IV (in combination with single or dual oral). Primary outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were any hemorrhage, favorable functional status (mRS 0-2) at 90 days, successful reperfusion (mTICI score ≥ 2b), in-stent thrombosis, and mortality at 90 days. Of the total 691 patients, 595 were included in the final analysis. One hundred and nineteen (20%) received no antiplatelets, 134 (22.5%) received single oral, 152 (25.5%) dual oral, and 196 (31.9%) IV combination. No significant association was found for sICH (ref: no antiplatelet: 5.7%; single:4.2%; aOR 0.64, CI 0.20-2.06, p = 0.45, dual:1.9%; aOR 0.35, CI 0.09-1.43, p = 0.15, IV combination: 6.1%; aOR 1.05, CI 0.39-2.85, p = 0.92). No association was found for parenchymal or petechial hemorrhage. Odds of successful reperfusion were significantly higher with dual oral (aOR 5.85, CI 2.12-16.14, p = 0.001) and IV combination (aOR 2.35, CI 1.07-5.18, p = 0.035) compared with no antiplatelets. Odds of excellent reperfusion (mTICI 2c/3) were significantly higher for cangrelor (aOR 4.41; CI 1.2-16.28; p = 0.026). No differences were noted for mRS 0-2 at 90 days, in-stent thrombosis, and mortality rates. Administration of dual oral and IV (in combination with single or dual oral) antiplatelets during EVT was associated with significantly increased odds of successful reperfusion without an increased rate of symptomatic hemorrhage or mortality in patients with anterior circulation TLs.
PubMed: 38017258
DOI: 10.1007/s12975-023-01214-9 -
The American Journal of Cardiology Sep 2023Direct oral anticoagulants (DOACs) are a favored treatment to prevent stroke in patients with atrial fibrillation (AF). There are limited data concerning the efficacy...
Direct oral anticoagulants (DOACs) are a favored treatment to prevent stroke in patients with atrial fibrillation (AF). There are limited data concerning the efficacy and safety of DOACs in obese. Obesity leads to wide structural and physiological changes that may affect the pharmacokinetics and pharmacodynamics of drugs. The optimal dosing strategies for DOACs in this significant and growing sub-group remain unknown. The study aimed to evaluate on a large scale the safety and efficacy of DOAC treatment in extreme obese patients with AF. In this retrospective cohort study, we included patients with AF treated with DOACs. Patients were divided according to body mass index (BMI). Study outcomes included stroke, major bleeding, and death. Between 2012 and 2017, 5183 patients with AF were included in the analysis (2,688, 2137, and 358 patients had a BMI <30, 30 to 40, and >40 accordingly). There was no significant difference in the prevalence of ischemic events (9.9%, 8.2%, and 7.5% of patients with BMI <30, 30 to 40, and >40, respectively, p = 0.088), major bleeding events (13%, 14.1%, and 11.2% of patients with BMI <30, 30 to 40, and >40, respectively, p value = 0.257) or net ischemic and major bleeding events (18.7%, 18.7%, and 15.4% of patients with BMI <30, 30 to 40, and >40 respectively, p = 0.297) between the BMI groups. In conclusion, DOACs treatment for prevention of ischemic events in AF is effective and safe through the BMI spectrum, including extreme obesity.
Topics: Humans; Atrial Fibrillation; Warfarin; Anticoagulants; Retrospective Studies; Stroke; Hemorrhage; Obesity; Administration, Oral
PubMed: 37473672
DOI: 10.1016/j.amjcard.2023.06.079