RESUMEN
The mechanism of action of selective serotonin reuptake inhibitors (SSRI) is still not properly established. It is essential to consider their positive and negative side effects before prescribing. In this article, we describe several of these side effects in the context of common pathologies and clinical situations. We discuss their cardioprotective effect and their role in the functional recovery of patients following stroke. We recall the increase in the risk of bleeding when prescribing SSRI concomitantly with antiaggregating and anticoagulant treatments. Prescribing SSRI also increases the risk of fracture and the frequency of hyponatremia. In the context of COPD, the effects of SSRI are more difficult to establish.
Le mécanisme d'action des antidépresseurs inhibiteurs sélectifs de la recapture de la sérotonine (ISRS) n'est toujours pas formellement établi. Il est essentiel de prendre en compte leurs effets secondaires positifs et négatifs pour leur prescription. Dans cet article, nous décrivons plusieurs de ces effets dans le contexte de pathologies et situations cliniques courantes. Nous abordons leur effet cardioprotecteur ainsi que leur rôle dans la récupération fonctionnelle des patients à la suite des accidents vasculaires cérébraux. Nous rappelons la majoration du risque hémorragique lors de la prescription d'ISRS en concomitance de traitements antiagrégants et anticoagulants. La prescription d'ISRS augmente également le risque fracturaire et la fréquence d'une hyponatrémie. Dans le contexte de la bronchopneumopathie chronique obstructive, les effets d'un ISRS sont plus difficiles à établir.
Asunto(s)
Inhibidores Selectivos de la Recaptación de Serotonina , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Antidepresivos/efectos adversos , Antidepresivos/farmacología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/inducido químicamente , Hemorragia/inducido químicamente , Fracturas Óseas/prevención & control , Fracturas Óseas/inducido químicamenteRESUMEN
Guidelines help to facilitate treatment decisions based on available evidence, and also to provide recommendations in areas of uncertainty. In this paper, we compare the recommendations for stroke workup and secondary prevention of ischemic stroke and transient ischemic attack of the American Heart Association (AHA)/American Stroke Association (ASA) with the European Stroke Organization (ESO) guidelines. The primary aim of this paper is to offer clinicians guidance by identifying areas where there is consensus and where consensus is lacking, in the absence or presence of high-level evidence. We compared AHA/ASA with the ESO guideline recommendations for 7 different topics related to diagnostic stroke workup and secondary prevention. We categorized the recommendations based on class and level of evidence to determine whether there were relevant differences in the ratings of evidence that the guidelines used for its recommendations. Finally, we summarized major topics of agreement and disagreement, while also prominent knowledge gaps were identified. In total, we found 63 ESO and 82 AHA/ASA recommendations, of which 38 were on the same subject. Most recommendations are largely similar, but not all are based on high-level evidence. For many recommendations, AHA/ASA and ESO assigned different levels of evidence. For the 10 recommendations with Level A evidence (high quality) in AHA/ASA, ESO only labeled 4 of these as high quality. There are many remaining issues with either no or insufficient evidence, and some topics that are not covered by both guidelines. Most ESO and AHA/ASA Guideline recommendations for stroke workup and secondary prevention were similar. However not all were based on high-level evidence and the appointed level of evidence often differed. Clinicians should not blindly follow all guideline recommendations; the accompanying level of evidence informs which recommendations are based on robust evidence. Topics with lower levels of evidence, or those with recommendations that disagree or are missing, may be an incentive for further clinical research.
Asunto(s)
Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Guías de Práctica Clínica como Asunto , Prevención Secundaria , Humanos , Ataque Isquémico Transitorio/prevención & control , Ataque Isquémico Transitorio/diagnóstico , Prevención Secundaria/métodos , Prevención Secundaria/normas , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/diagnóstico , Europa (Continente) , Estados Unidos , American Heart Association , Medicina Basada en la Evidencia/normas , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/diagnósticoRESUMEN
BACKGROUND: Associations of dietary sodium and potassium intake with fracture risk are inconsistent and the effects of salt substitute on fracture incidence are unknown. We assessed the effect of salt substitute compared to regular salt intake on fracture incidence using data from the Salt Substitute and Stroke Study (SSaSS). METHODS: SSaSS was a cluster-randomized controlled trial conducted in 600 villages in northern China. Villages were randomly allocated into intervention and control groups in a 1:1 ratio. Salt substitute was provided to intervention villages and control villages continued regular salt use for 5 years. The primary outcome for this secondary analysis was the incidence of all fractures. Secondary outcomes included incidence of vertebral fracture, non-vertebral fracture, and fracture of unknown or non-specific location. RESULTS: 20,995 participants were included in this study, and 821 fractures occurred during follow-up. Intention-to-treat analyses showed no differences between the salt substitute and regular salt groups in the incidence of all fractures (rate ratio (RR) 0.96; 95% CI 0.81 to 1.14), vertebral fracture (RR 0.82; 95% CI 0.53 to 1.26), non-vertebral fracture (RR 1.05; 95% CI 0.86 to 1.29), or fracture of unknown or non-specific location (RR 0.80; 95% CI 0.54 to 1.18). CONCLUSIONS: Use of salt substitute compared to regular salt had no detectable effect on the incidence of fracture in a population at high risk of cardiovascular disease and fracture. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02092090. Registered on March 12, 2014.
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Fracturas Óseas , Cloruro de Sodio Dietético , Humanos , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Fracturas Óseas/epidemiología , Anciano , Cloruro de Sodio Dietético/efectos adversos , Cloruro de Sodio Dietético/administración & dosificación , Incidencia , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & controlRESUMEN
BACKGROUND: The lipid-lowering effects of Omega-3 fatty acids have been widely reported, yet their impact on ischemic stroke remains controversial. Reports on the protective effects of unsaturated fatty acids, such as Omega-6 and Omega-7, as well as saturated fatty acids in cardiovascular diseases, including hypertension and ischemic stroke, are less frequent. OBJECTIVES: This study aims to identify fatty acids associated with blood pressure and ischemic stroke through Mendelian randomization. Besides, it seeks to determine whether specific fatty acids can prevent ischemic stroke by managing blood pressure and revealing the specific mechanisms of this action. METHODS: This research involved downloading relevant data from websites and extracting SNPs that met the standard criteria as instrumental variables. Simultaneously, the 'MR-PRESSO' package and 'Mendelian Randomization' package were used to eliminate confounding SNPs that could bias the study results. Then, inverse variance weighting and the weighted median were employed as primary analysis methods, accompanied by sensitivity analysis to assess the validity of the causal relationships. Initially, multivariable Mendelian randomization was used to identify fatty acids linked to blood pressure and the incidence of ischemic stroke. The causal link between certain fatty acids and the initiation of ischemic stroke was then investigated using bidirectional and mediator Mendelian randomization techniques. Stepwise Regression and the Product of Coefficients Method in mediator Mendelian randomization were utilized to ascertain whether specific fatty acids reduce ischemic stroke risk by lowering blood pressure. RESULTS: Multivariable Mendelian randomization analysis indicated a potential inverse correlation between Omega-3 intake and both blood pressure and ischemic stroke. Consequently, Omega-3 was selected as the exposure, with blood pressure and ischemic stroke-related data as outcomes, for further bidirectional and mediation Mendelian Randomization analyses. Bidirectional Mendelian Randomization revealed that Omega-3 significantly influences DBP (P = 1.01e-04) and IS (P = 0.016). It also showed that DBP and SBP significantly affect LAS, SVS, CES, IS, and LS. Mediator Mendelian Randomization identified five established mediating pathways: Omega-3-Diastolic blood pressure-Small vessel stroke, Omega-3-Diastolic blood pressure-Cardioembolic stroke, Omega-3-Diastolic blood pressure-Lacunar stroke, Omega-3-Diastolic blood pressure-Large artery atherosclerosis stroke, and Omega-3-Diastolic blood pressure-Ischemic stroke. Of these, four pathways are complete mediation, and one pathway is partial mediation. CONCLUSIONS: The findings suggest that Omega-3 may indirectly reduce the incidence of ischemic stroke by lowering blood pressure. Thus, blood pressure modulation might be one of the mechanisms through which Omega-3 prevents ischemic stroke. In summary, incorporating an increased intake of Omega-3 in the diet can serve as one of the dietary intervention strategies for patients with hypertension. Additionally, it can act as an adjunctive therapy for the prevention of ischemic strokes and their complications.
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Presión Sanguínea , Ácidos Grasos Omega-3 , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Accidente Cerebrovascular , Ácidos Grasos Omega-3/uso terapéutico , Humanos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/genética , Hipertensión/genética , Factores de RiesgoRESUMEN
BACKGROUND: Direct oral anticoagulants (DOACs) have complex dosing regimens and are often incorrectly prescribed. We evaluated a nationwide DOAC population management dashboard rollout whose purpose includes pharmacist review and correction of off-label dosing prescriptions. METHODS AND RESULTS: Using data from Veterans Health Affairs, we identified all patients prescribed DOACs for atrial fibrillation or venous thromboembolism between August 2015 and December 2019. Sites were grouped on the basis of the timing of moderate-high usage of the DOAC population management tool dashboard. Effectiveness was defined as the monthly rate of off-label DOAC prescribing and the rate of clinical adverse events (bleeding, composite of stroke or venous thromboembolism). Implementation was evaluated as the percentage of off-label DOAC prescriptions changed within 7 days. Among the 128 652 patients receiving DOAC therapy at 123 centers, between 6.9% and 8.6% had off-label DOAC prescriptions. Adoption of the DOAC population management tool dashboard before July 2018 was associated with a decline in off-label dosing prescriptions (8.7%-7.6%). Only 1 group demonstrated a significant reduction in monthly rates of bleeding following implementation. All sites experienced a reduction in the composite of venous thromboembolism or stroke following dashboard adoption. There was no difference in the implementation outcome of DOAC prescription change within 7 days in any of the adoption groups. CONCLUSIONS: Early adoption of the DOAC population management tool dashboard was associated with decreased rates of off-label DOAC dosing prescription and reduced bleeding. Following adoption of the DOAC population management tool dashboard, all sites experienced reductions in venous thromboembolism and stroke events.
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Fibrilación Atrial , Uso Fuera de lo Indicado , Farmacéuticos , Tromboembolia Venosa , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Estados Unidos , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/epidemiología , Femenino , Masculino , Anciano , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Administración Oral , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Pautas de la Práctica en Medicina/normas , Prescripciones de Medicamentos/estadística & datos numéricos , United States Department of Veterans AffairsRESUMEN
BACKGROUND: Patients with atrial fibrillation are frequently nonadherent to oral anticoagulants (OACs) prescribed for stroke and systemic embolism (SSE) prevention. We quantified the relationship between OAC adherence and atrial fibrillation clinical outcomes using methods not previously applied to this problem. METHODS AND RESULTS: Retrospective observational cohort study of incident cases of atrial fibrillation from population-based administrative data over 23 years. The exposure of interest was proportion of days covered during 90 days before an event or end of follow-up. Cox proportional hazard models were used to evaluate time to first SSE and the composite of SSE, transient ischemic attack, or death and several secondary outcomes. A total of 44 172 patients were included with median follow-up of 6.7 years. For direct OACs (DOACs), each 10% decrease in adherence was associated with a 14% increased hazard of SSE and 5% increased hazard of SSE, transient ischemic attack, or death. For vitamin K antagonist (VKA) the corresponding increase in SSE hazard was 3%. Receiving DOAC or VKA was associated with primary outcome hazard reduction across most the proportion of days covered spectrum. Differences between VKA and DOAC were statistically significant for all efficacy outcomes and at most adherence levels. CONCLUSIONS: Even small reductions in OAC adherence in patients with atrial fibrillation were associated with significant increases in risk of stroke, with greater magnitudes for DOAC than VKA. DOAC recipients may be more vulnerable than VKA recipients to increased risk of stroke and death even with small reductions in adherence. The worsening efficacy outcomes associated with decreasing adherence occurred without the benefit of major bleeding reduction.
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Anticoagulantes , Fibrilación Atrial , Cumplimiento de la Medicación , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Anciano , Cumplimiento de la Medicación/estadística & datos numéricos , Administración Oral , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Persona de Mediana Edad , Factores de Tiempo , Anciano de 80 o más Años , Resultado del Tratamiento , Embolia/prevención & control , Embolia/epidemiología , Embolia/etiología , Factores de Riesgo , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/prevención & controlRESUMEN
OBJECTIVES: To explore the acceptability and feasibility of detection of atrial fibrillation (AF) by emergency medical services (EMS) and identify potential barriers and facilitators to implementing a formal pathway to facilitate follow-up in primary care, which could reduce the risk of AF-related stroke. DESIGN: Qualitative study using focus groups and one-to-one interviews guided by a semistructured topic guide. SETTING: North East England. PARTICIPANTS: Focus groups with 18 members of the public and one-to-one online interviews with 11 healthcare and service providers (six paramedics and five experts representing cardiology, general practice (GP), public health, research, policy and commissioning). RESULTS: All participant groups were supportive of a role of EMS in identifying AF as part of routine assessment and formalising the response to AF detection. However, this should not create delays for EMS since rate-controlled AF is non-urgent and alternative community mechanisms exist to manage it. Public participants were concerned about communication of the AF diagnosis and whether this should be 'on scene' or in a subsequent GP appointment. Paramedics reported frequent incidental identification of AF, but it is not always clear 'on scene' that this is a new diagnosis, and there is variation in practice regarding whether (and how) this is communicated to the GP. Paramedics also focused on ensuring the safety of non-conveyed patients and a perceived need for an 'active' reporting process, so that a finding of AF was actioned. Field experts felt that a formal pathway would be useful and favoured a simple intervention without adding to time pressures unnecessarily. CONCLUSIONS: There is support for the development of a formal pathway to ensure follow-up for people with AF that is incidentally detected by EMS. This has the potential to improve anticoagulation rates and reduce the risk of stroke.
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Ambulancias , Fibrilación Atrial , Servicios Médicos de Urgencia , Grupos Focales , Investigación Cualitativa , Humanos , Fibrilación Atrial/terapia , Inglaterra , Masculino , Femenino , Persona de Mediana Edad , Adulto , Accidente Cerebrovascular/prevención & control , Anciano , Entrevistas como Asunto , Atención Primaria de Salud , Actitud del Personal de SaludRESUMEN
This study pooled data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial to estimate the treatment effect of intensive BP on stroke prevention, and investigate whether stroke risk score impacted treatment effect. Of all the potential manifestations of the hypertension, the most severe outcomes were stroke or death. A composite endpoint of time to death or stroke (stroke-free survival [SFS]), whichever occurred first, was defined as the outcome of interest. Participants without prevalent stroke were stratified into stroke risk tertiles based on the predicted revised Framingham Stroke Risk Score. The stratified Cox model was used to calculate the hazard ratio (HR) for the intensive BP treatment. 834 (5.92%) patients had SFS events over a median follow-up of 3.68 years. A reduction in the risk for SFS was observed among the intensive BP group as compared with the standard BP group (HR: 0.76, 95% CI: 0.65, 0.89; risk difference: 0.98([0.20, 1.76]). Further analyses demonstrated the significant benefit of intensive BP treatment on SFS only among participants having a high stroke risk (risk tertile 1: 0.76 [0.52, 1.11], number needed to treat [NNT] = 861; risk tertile 2: 0.87[0.65, 1.16], NNT = 91; risk tertile 3: 0.69[0.56, 0.86], NNT = 50). Intensive BP treatment lowered the risk of SFS, particularly for those at high risk of stroke.
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Antihipertensivos , Presión Sanguínea , Hipertensión , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Persona de Mediana Edad , Hipertensión/tratamiento farmacológico , Hipertensión/complicaciones , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/mortalidad , Factores de Riesgo , Modelos de Riesgos ProporcionalesRESUMEN
(1) Background: Estimating the causal association between nutrient intake, as a modifiable risk factor, and stroke risk is beneficial for the prevention and management of stroke. However, observational studies are unavoidably influenced by confounding factors and reverse causation. (2) Methods: We performed a two-sample Mendelian randomization (MR) to estimate the effects of nutrient intake on stroke risk. Summary statistics for nutrients, including 4 macronutrients and 14 micronutrients, were derived from 15 genome-wide association studies (GWAS). Data on stroke and its subtypes were sourced from the MEGASTROKE consortium. (3) Results: Genetically predicted magnesium levels, as the protective factors, were significantly associated with a lower risk of cardioembolic stroke (OR: 0.011, 95% CI: 0-0.25, p-value: 0.005) in the IVW method. Additionally, vitamin C reduced the risk of cardioembolic stroke (OR: 0.759, 95% CI: 0.609-0.946, p-value: 0.014) and vitamin B9 reduced the risk of small vessel stroke (OR: 0.574, 95% CI: 0.393-0.839, p-value: 0.004) with the IVW method. However, the association of vitamin B6 with an increased risk of large-artery stroke (OR: 1.546, 95% CI: 1.009-2.37, p-value: 0.046) in the Wald ratio method should be interpreted cautiously due to the limited number of SNPs. There was also suggestive evidence that magnesium might decrease the risk of both any stroke and ischemic stroke. (4) Conclusions: Our MR analysis highlights the protective roles of magnesium, vitamin C, and vitamin B9 in stroke prevention, making them key targets for public health strategies. However, the findings related to vitamin B6 are less certain and require further validation.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Micronutrientes , Nutrientes , Accidente Cerebrovascular , Humanos , Micronutrientes/administración & dosificación , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Factores de Riesgo , Polimorfismo de Nucleótido Simple , Magnesio/administración & dosificación , DietaRESUMEN
BACKGROUND: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. METHODS: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. CONCLUSION: The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. TRIAL REGISTRATION: ClinicalTrials.gov NCT05757869.
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Fibrilación Atrial , Inhibidores del Factor Xa , Pirazoles , Piridonas , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Piridonas/efectos adversos , Método Doble Ciego , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Masculino , Femenino , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Aleteo Atrial/complicaciones , Hemorragia/inducido químicamente , Persona de Mediana Edad , Anciano , Factor XIa/antagonistas & inhibidores , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversosRESUMEN
Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke. Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke. Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024. Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined. Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage. Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]). Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.
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Aspirina , Inhibidores del Factor Xa , Accidente Cerebrovascular Isquémico , Neoplasias , Pirazoles , Piridonas , Humanos , Piridonas/uso terapéutico , Piridonas/efectos adversos , Masculino , Femenino , Aspirina/uso terapéutico , Aspirina/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Anciano , Persona de Mediana Edad , Método Doble Ciego , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/epidemiología , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Hemorragia/inducido químicamenteRESUMEN
BACKGROUND: Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device-detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device-detected AF but with no ECG-documented AF is unclear. METHODS AND RESULTS: This prespecified analysis of the NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device-detected AF with and without a prior stroke or TIA in the randomized, double-blind, double-dummy NOAH-AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device-detected AF randomized in the NOAH-AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time-to-event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient-year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient-year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient-year]; no anticoagulation: 6 out of 131 [2.3% per patient-year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients). CONCLUSIONS: Anticoagulation appears to have ambiguous effects in patients with device-detected AF and a prior stroke or TIA in this hypothesis-generating analysis of the NOAH-AFNET 6 in the absence of ECG-documented AF, partially due to a low rate of stroke without anticoagulation.
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Anticoagulantes , Fibrilación Atrial , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Ataque Isquémico Transitorio/prevención & control , Ataque Isquémico Transitorio/etiología , Femenino , Anciano , Masculino , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Método Doble Ciego , Administración Oral , Anciano de 80 o más Años , Resultado del Tratamiento , Hemorragia/inducido químicamente , Factores de Tiempo , Marcapaso ArtificialRESUMEN
BACKGROUND: Despite oral anticoagulation, patients with atrial fibrillation (AF) remain at risk of ischemic stroke and systemic embolism (SE) events. For patients whose residual risk is sufficiently high, additional therapies might be useful to mitigate stroke risk. METHODS AND RESULTS: Individual patient data from 5 landmark trials testing oral anticoagulation in AF were pooled in A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in AF (COMBINE AF). We calculated the rate of ischemic stroke/SE among oral anticoagulation-treated patients with a CHA2DS2-VASc score≥2, across strata of CHA2DS2-VASc score, stroke history, and AF type, as either paroxysmal or nonparoxysmal. We included 71 794 patients with AF (median age 72 years, interquartile range, 13 years, 61.3% male) randomized to a direct oral anticoagulant or vitamin K antagonist, and followed for a mean of 2.1 (±0.8) years. The median CHA2DS2-VASc score was 4 (interquartile range, 3-5), 18.8% had a prior stroke, and 76.4% had nonparoxysmal AF. The overall rate of stroke/SE was 1.33%/y (95% CI, 1.27-1.39); 1.38%/y (95% CI, 1.31-1.45) for nonparoxysmal AF, and 1.15%/y (95% CI, 1.05-1.27) for paroxysmal AF. The rate of ischemic stroke/SE increased by a rate ratio of 1.36 (95% CI, 1.32-1.41) per 1-point increase in CHA2DS2-VASc, reaching 1.67%/y (95% CI, 1.59-1.75) ≥4 CHA2DS2-VASc points. Patients with both nonparoxysmal AF and CHA2DS2-VASc ≥4 had a stroke/SE rate of 1.75%/y (95% CI, 1.66-1.85). In patients with a prior stroke, the risk was 2.51%/y (95% CI, 2.33-2.71). CONCLUSIONS: AF type, CHA2DS2-VASc score, and stroke history can identify patients with AF, who despite oral anticoagulation have a residual stroke/SE risk of 1.5% to 2.5% per year. Evaluation of additional stroke/SE prevention strategies in high-risk patients is warranted.
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Anticoagulantes , Fibrilación Atrial , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Administración Oral , Medición de Riesgo , Factores de Riesgo , Anciano , Femenino , Masculino , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/diagnóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Persona de Mediana Edad , Anciano de 80 o más AñosAsunto(s)
Estenosis de la Válvula Aórtica , Accidente Cerebrovascular , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Estenosis de la Válvula Aórtica/cirugía , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Factores de Riesgo , Resultado del Tratamiento , Medición de RiesgoAsunto(s)
Foramen Oval Permeable , Guías de Práctica Clínica como Asunto , Recurrencia , Prevención Secundaria , Dispositivo Oclusor Septal , Accidente Cerebrovascular , Humanos , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/cirugía , Foramen Oval Permeable/terapia , Prevención Secundaria/métodos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Cateterismo Cardíaco/instrumentación , Cateterismo Cardíaco/métodosAsunto(s)
Cardiopatías Congénitas , Accidente Cerebrovascular , Humanos , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/epidemiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Adulto , Factores de Riesgo , Medición de RiesgoRESUMEN
Direct oral anticoagulants (DOACs) changed stroke prevention and decreased the risk of ischemic and hemorrhagic complications in patients on oral anticoagulation (OAC) therapy. The numbers of patients prescribed DOACs has increased rapidly. Availability of specific reversal agents opened new avenues in the prevention and management of DOAC complications. An ideal specific reversal agent for a DOAC in acute stroke is an agent which lacks safety concerns and immediately reverses DOAC anticoagulation activity, thereby enabling effective treatment. Reversal of anticoagulant activity is mandatory in patients with acute ischemic stroke (AIS) before performing therapeutic procedures such as intravenous thrombolysis (IVT) and neurosurgery in intracranial hemorrhage (ICH) in order to improve clinical outcomes. In this manuscript we pursue an interdisciplinary approach in discussing advantages and concerns of specific reversal agents in acute stroke DOAC-treated patients in everyday clinical practice.
Asunto(s)
Anticoagulantes , Accidente Cerebrovascular , Humanos , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Administración Oral , Accidente Cerebrovascular Isquémico/tratamiento farmacológicoRESUMEN
BACKGROUND: Individuals with diabetes exhibit a higher risk of cardiovascular disease and mortality compared to healthy individuals. Following a transient ischemic attack (TIA) the risk of stroke and death increase further. Physical activity engagement after a TIA is an effective way of secondary prevention. However, there's a lack of research on how individuals with diabetes modify physical activity levels and how these adjustments impact survival post-TIA. This study aimed to determine the extent to which individuals with diabetes alter their physical activity levels following a TIA and to assess the impact of these changes on mortality. METHODS: This was a nationwide longitudinal study, employing data from national registers in Sweden spanning from 01/01/2003 to 31/12/2019. Data were collected 2 years retro- and prospectively of TIA occurrence, in individuals with diabetes. Individuals were grouped based on decreasing, remaining, or increasing physical activity levels after the TIA. Cox proportional hazards models were fitted to evaluate the adjusted relationship between change in physical activity and all-cause, cardiovascular, and non-cardiovascular mortality. RESULTS: The final study sample consisted of 4.219 individuals (mean age 72.9 years, 59.4% males). Among them, 35.8% decreased, 37.5% kept steady, and 26.8% increased their physical activity after the TIA. A subsequent stroke occurred in 6.7%, 6.4%, and 6.1% of individuals, while death occurred in 6.3%, 7.3%, and 3.7% of individuals, respectively. In adjusted analyses, participants who increased their physical activity had a 45% lower risk for all-cause mortality and a 68% lower risk for cardiovascular mortality, compared to those who decreased their physical activity. CONCLUSIONS: Positive change in physical activity following a ΤΙΑ was associated with a reduced risk of mortality. Increased engagement in physical activity should be promoted after TIA, thereby actively supporting individuals with diabetes in achieving improved health outcomes.