Abstract
Introduction
Atrial fibrillation (AF) is associated with dementia. Anticoagulation may modify this relationship, but it is unclear if this is due to stroke reduction alone.
Methods
Age- ...and sex-matched individuals from the U.K. Clinical Practice Research Datalink (2008–2016) with and without an incident diagnosis of AF were followed for a new dementia diagnosis. We estimated adjusted hazard ratios (aHRs) for incident dementia diagnosis in the AF cohort, overall and stratified by anticoagulation status, using the matched non-AF cohorts as reference. We performed a sensitivity analysis excluding individuals with stroke/transient ischaemic attack (TIA) before the observation period.
Results
Over 193,082 person-years (mean follow-up 25.7 ± 0.1 months), 347/15,276 AF (2.3%) and 1,085/76,096 non-AF (1.4%) were newly diagnosed with dementia (aHR, 1.31, 95% confidence interval, 1.15–1.49). The AF group had more co-morbidity and higher rates of dementia, both with and without anticoagulation, than non-AF. When those with history of stroke/ TIA before the observation period were excluded and those with incident stroke/TIA during the observation period were censored, AF individuals not on anticoagulation had significantly higher rates of dementia compared with non-AF, aHR 1.30 (1.06–1.58).
Conclusion
Our findings support the hypothesis that AF is a distinct risk factor for dementia, independent of stroke/TIA and other vascular risk factors. In those without stroke/TIA, risk of dementia is increased only in those who are not on anticoagulation, suggesting anticoagulation is protective presumably through reduction of sub-clinical embolic events. Further prospective research is needed to better ascertain the role of anticoagulation amongst targeted therapeutic strategies to reduce cognitive decline in AF.
Abstract Research on cerebrovascular events in atrial fibrillation (AF) patients taking non‐vitamin K antagonist oral anticoagulants (NOACs) with antiseizure medications (ASMs) is limited, ...highlighting a significant gap in literature. We assessed thrombotic and hemorrhagic risks in patients on NOACs and ASMs versus those on NOACs or ASMs alone. We analyzed a retrospective cohort from five centers, including AF and epilepsy patients on both medications ( n = 188), AF patients on NOACs ( n = 298), and epilepsy patients on ASMs ( n = 50), with a 3‐year follow‐up. Propensity score matching adjusted for cardiovascular risk differences. The primary outcomes were ischemic stroke, transient ischemic attack, and major bleeding. Results showed the ASM+NOAC group had a higher risk of primary outcomes compared to the NOAC‐only group (5.68% vs. 1.18%, hazard ratio = 5.72, 95% confidence interval = 2.22–14.73), with no events in the ASM‐only group. This suggests an increased risk for patients on combined NOAC and ASM therapy, underlining the need for careful drug interaction consideration.
Anticoagulant treatment in patients with primary and metastatic brain cancer is a concern due to risk of intracranial hemorrhage (ICH). We performed a systematic review and meta-analysis to evaluate ...the risk of ICH in patients with primary or metastatic brain cancer treated with or without anticoagulants. Articles on ICH in patients with primary or metastatic brain cancer treated with or without anticoagulants published up to September 2021 were identified by searching PubMed, EMBASE, and Cochrane Library databases. The primary outcome of this analysis was ICH. Thirty studies were included. Rate of ICH was 13.0% in 1009 patients with metastatic brain cancer and 6.4% in 2353 patients with primary brain cancer (relative risk RR, 3.26; 95% confidence interval CI, 2.69-3.94; I2 = 92.8%). In patients with primary brain cancer, ICH occurred in 12.5% and 4.4% of patients treated with or without anticoagulants, respectively (11 studies, 659 treated and 1346 not treated patients; RR, 2.63; 95% CI, 1.48-4.67; I2 = 49.6%). In patients with metastatic brain cancer, ICH occurred in 14.7% and 15.4% (5 studies, 265 treated and 301 not treated patients; RR, 0.92; 95% CI, 0.43-1.93; I2 = 0%). ICH occurred in 8.3% of 172 treated with direct oral anticoagulants (DOACs) and in 11.7% of 278 treated with low-molecular weight heparin (LMWH) (5 studies; RR, 0.44; 95% CI, 0.25-0.79; I2 = 0%). Patients with metastatic brain cancer have a particularly high risk of ICH. Patients with primary brain cancer have an increased risk of ICH during anticoagulation. DOACs are associated with a lower risk of ICH than LMWH.
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About 15% of patients with cancer experience one or more episodes of venous thromboembolism (VTE) during the course of their disease. In patients with cancer, VTE has a substantial impact on the ...quality of life and care.
Current guidelines recommend low-molecular-weight heparin (LMWH) as first choice therapy for long-term anticoagulation in cancer patients with VTE. However, there are several practical issues concerning the long-term use of these anticoagulants.
In the last years, several direct oral anticoagulants (DOACs) have emerged as alternatives to heparins and vitamin K antagonists for the treatment of VTE, but data regarding both efficacy and safety of DOACs in the subgroup of patients with cancer treatments were limited. The results of two studies evaluating the clinical benefit of treatment of VTE with direct oral anticoagulants in patients with cancer have been recently presented. Several studies comparing DOACs with LMWH are currently ongoing.
Abstract
Background
Venous thromboembolism (VTE) is a major cause of death in cancer patients. Although patients with cancer have numerous risk factors for VTE, the relative contribution of cancer ...treatments is unclear.
Objective
The objective of this study is to evaluate the association between cancer therapies and the risk of VTE.
Methods
From UK Clinical Practice Research Datalink, data on patients with first cancer diagnosis between 2008 and 2016 were extracted along with information on hospitalization, treatments, and cause of death. Primary outcome was active cancer-associated VTE. To establish the independent effects of risk factors, adjusted subhazard ratios (adj-SHR) were calculated using Fine and Gray regression analysis accounting for death as competing risk.
Results
Among 67,801 patients with a first cancer diagnosis, active cancer-associated VTE occurred in 1,473 (2.2%). During a median observation time of 1.2 years, chemotherapy, surgery, hormonal therapy, radiation therapy, and immunotherapy were given to 71.1, 37.2, 17.2, 17.5, and 1.4% of patients with VTE, respectively. The active cancers associated with the highest risk of VTE—as assessed by incidence rates—included pancreatic cancer, brain cancer, and metastatic cancer. Chemotherapy was associated with an increased risk of VTE (adj-SHR: 3.17, 95% confidence interval CI: 2.76–3.65) while immunotherapy with a not significant reduced risk (adj-SHR: 0.67, 95% CI: 0.30–1.52). There was no association between VTE and radiation therapy (adj-SHR: 0.91, 95% CI: 0.65–1.27) and hormonal therapies.
Conclusion
VTE risk varies with cancer type. Chemotherapy was associated with an increased VTE risk, whereas with radiation and immunotherapy therapy, an association was not confirmed.
Patients aged 90 years or older are often excluded from or under-represented in clinical trials and cohort studies. The clinical benefit of anticoagulation in nonagenarians with atrial fibrillation ...(AF) remains undefined.
To assess the effectiveness and safety of oral anticoagulants in AF patients aged 90 years or older.
Non-valvular AF patients aged 90 years or older receiving direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) were included in this observational multicentre study. The primary outcome was the composite of ischaemic stroke/transient ischemic attack (TIA) and systemic embolism (SE). Major bleeding (MB), anticoagulant discontinuation and all-cause death were also assessed. Results are reported as sub-distribution hazard ratios (SHR) with 95% CI, taking death as competing risk.
546 patients were included (301 VKAs retrospective cohort and 245 DOACs prospective cohort; median follow-up 404 days). The rate of ischaemic stroke/TIA/SE was 2.4% patient-year and that of MB 5.5% patient-year. Previous ischaemic stroke/TIA (SHR 3.47; 95% CI 1.54–7.81) and vascular disease (SHR 2.89; 95% CI 1.27–6.60) were independent predictors of ischaemic stroke/TIA/SE. Previous bleeding (SHR 2.53; 95% CI 1.37–4.64) was an independent predictor of MB. The risk of ischaemic stroke/TIA/SE (SHR 0.78, 95% CI 0.30–2.04) or MB (SHR 1.43, 95% CI 0.77–2.65) was not significantly different with DOACs or VKAs.
In AF nonagenarians receiving anticoagulant treatment, the rate of ischaemic stroke/TIA/SE is relatively low with the drawback of a not negligible rate of MB. DOACs seem a reasonable option for prevention of ischaemic stroke/TIA/SE in this setting.
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•The benefit of anticoagulation in atrial fibrillation (AF) nonagenarians is unknown.•In AF nonagenarians, anticoagulants seem to be safely and effectively administered.•Further studies are needed to validate our results in unselected AF nonagenarians.
Major bleeding occurs in about 4% of patients while on treatment with direct oral anticoagulants (DOACs). The case-fatality rate associated with these events is estimated to be about 5%. The specific ...roles of antidotes, when used with DOACs in reducing the case fatality or improving the overall clinical course of these events, are not thoroughly understood. To this regard, the US Food and Drug Administration as well as European Medicines Agency have recently licensed idarucizumab for the management of patients with life-threatening bleeding or the need for urgent surgery/procedures while on treatment with dabigatran. Specifically, idarucizumab is a humanized monoclonal antibody fragment that rapidly reverses the anticoagulant effect of dabigatran. Two other antidotes, andeXanet and ciraparantag are currently under evaluation for reversal of DOACs. Here, we report on the use of idarucizumab in two patients who experienced life-threatening bleeding while on treatment with dabigatran for atrial fibrillation and provide a review highlighting the need for antidotes use with DOACs.
•Thrombotic complications in patients with heart failure are an underappreciated problem.•We review data regarding coagulation disorders in acute and chronic heart failure.•We discuss scenarios where ...antiplatelet and anticoagulant therapy can be tailored.•We provide top 10 pearls in coagulation disorder management in heart failure.
Heart failure (HF) is a clinical syndrome that is divided into 3 subtypes based on the left ventricular ejection fraction. Every subtype has specific clinical characteristics and concomitant diseases, substantially increasing risk of thromboembolic complications, such as stroke, peripheral embolism and pulmonary embolism. Despite the annual prevalence of 1% and devastating clinical consequences, thromboembolic complications are not typically recognized as the leading problem in patients with HF, representing an underappreciated clinical challenge. Although the currently available data do not support routine anticoagulation in patients with HF and sinus rhythm, initial reports suggest that such strategy might be beneficial in a subset of patients at especially high thromboembolic risk. Considering the existing evidence gap, we aimed to review the currently available data regarding coagulation disorders in acute and chronic HF based on the insight from preclinical and clinical studies, to summarize the evidence regarding anticoagulation in HF in special-case scenarios and to outline future research directions so as to establish the optimal patient-tailored strategies for antiplatelet and anticoagulant therapy in HF. In summary, we highlight the top 10 pearls in the management of patients with HF and no other specific indications for oral anticoagulation therapy. Further studies are urgently needed to shed light on the pathophysiological role of platelet activation in HF and to evaluate whether antiplatelet or antithrombotic therapy could be beneficial in patients with HF.
Heart failure (HF) is a clinical syndrome divided into 3 subtypes on the basis of the left ventricular systolic function. Every subtype has specific clinical characteristics and concomitant diseases, substantially increasing the risk of thromboembolic complications, such as stroke, peripheral embolism and pulmonary embolism. Despite the annual prevalence of 1% and devastating clinical consequences, thromboembolic complications are not typically recognized as the leading problem in patients with HF, representing an underappreciated clinical challenge. Although the currently available data do not support routine anticoagulation in patients with HF and no atrial arrhythmia, initial reports suggest that such a strategy might be beneficial in a subset of patients at especially high risk of thrombotic complications. Considering the existing evidence gap, we aimed to review the currently available data regarding coagulation problems in stable and unstable patients with HF based on the insight from preclinical and clinical studies, to summarize the evidence regarding anticoagulation in HF in specific patient groups and to outline future research directions to establish the optimal strategies for antiplatelet and anticoagulant therapy in HF, tailored to the needs of an individual patient. In summary, we highlight the top 10 pearls in the management of patients with HF and no other specific indications for oral anticoagulation therapy.
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Abstract Background Persistence to treatment affects clinical outcomes in patients with chronic disease such as atrial fibrillation (AF). Methods This prospective cohort study included consecutive ...non-valvular AF patients prescribed with non-vitamin K oral anticoagulants (NOACs) and investigated for any permanent discontinuation at 1-year of this therapy, as well as any reasons for discontinuation. Results Overall, 1305 patients were prescribed with dabigatran (N = 473), rivaroxaban (N = 425) or apixaban (N = 407). Of these, 201 patients (15.4%) discontinued NOACs during the first year of treatment. More than 60% of these discontinuations occurred during the first 6 months. Reasons for discontinuation included: dyspepsia or abdominal pain in 38 patients (2.9%) and bleeding in 59 (4.5%). Discontinuation for the former occurred earlier (50% within 2 months) compared to the latter (66% after the first 4 months). The prescription of reduced NOAC doses resulted being an independent predictor of discontinuation (OR 1.74, 95% CI 1.23–2.45, p = 0.002). Regarding the use of dabigatran, rivaroxaban and apixaban, the following were observed: discontinuers were 22.0% (95% CI 18.5–25.9), 14.4% (95% CI 11.3–18.0) and 8.8% (95% CI 6.5–12.0), the risk of discontinuation associated with bleeding was 20.2%, 44.3% and 30.6% and dyspepsia or abdominal pain was 35.6%, 1.6% and 0%, respectively. Conclusion Discontinuation of NOACs in AF patients was relatively common and more than often occurred in the first six months after prescription. Patients treated with reduced doses of NOACs had a higher probability to discontinue compared to those who were prescribed conventional doses.
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