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The aim of the study was to evaluate the performance of the 2MACE in patients with atrial fibrillation (AF) treated with rivaroxaban and to improve the accuracy of 2MACE.This was a post-authorization and observational study of AF adults treated with rivaroxaban for ≥ 6 months. The primary endpoint was any of the major adverse cardiac events (MACE), namely, cardiovascular death, non-fatal myocardial infarction, and myocardial revascularization. The area under the curve (AUC) was calculated to evaluate the performance of 2MACE, and a new score, 2MACER to predict MACE.A total of 1433 patients were included (74.2 ± 9.7 years, CHA₂DS₂-VASc 3.5 ± 1.5, 26.9% 2MACE ≥ 3). The annual event rates (follow-up 2.5 years) were 1.07% for MACE, 0.66% for thromboembolic events and 1.04% for major bleeding. Patients with 2MACE ≥ 3 (vs.3) had higher risk of stroke/systemic embolism/transient ischemic attack (odds ratio [OR] 5.270; 95% CI 2.216-12.532), major bleeding (OR 4.624; 95% CI 2.163-9.882), MACE (OR 3.202; 95% CI 1.548-6.626) and cardiovascular death (OR 3.395; 95% CI 1.396-8.259). 2MACE was recalculated giving 1 more point to patients with baseline a glomerular filtration rate50 mL/min/1.73 m² (2MACER); 2MACER vs. 2MACE: IDI 0.1%, p = 0.126; NRI 23.9%, p = 0.125; AUC: 0.651 (95% CI 0.547-0.755) vs. 0.638 (95% CI 0.534-0.742), respectively; p = 0.361.In clinical practice, AF patients anticoagulated with rivaroxaban exhibit a low risk of events. 2MACE score acts as a modest predictor of a higher risk of adverse outcomes in this population. 2MACER did not significantly increase the ability of 2MACE to predict MACE.

Introduction and objectives Despite evidence of a reduction in the incidence and mortality of acute coronary syndrome (ACS), some studies have highlighted differences in outcomes between men and women. We aimed to explore sex differences in the management and treatment of patients with ACS in Spain. Methods This ecological cross-sectional study combined ACS data from 10 Spanish registries (54 centres). Meta-regression analysis was performed using aggregated data of baseline characteristics, interventional procedures, treatments, and events that occurred during hospitalization and one-year follow-up. Results Aggregated data from 34 605 patients (75.1% men) was included. ST-segment elevation myocardial infarction was the most frequent diagnosis (58.9%) and almost 80% of patients were Killip Class I. Compared to men, women were older (mean age: 71.0 vs 63.3 years) and presented higher rates of hypertension (68.1% vs 51.7%) and diabetes (37.7% vs 26.5%). Women were also less likely to undergo percutaneous coronary interventions, revascularization surgery, and to receive drug-eluting stents during hospitalization. Regarding to antiplatelet therapy, even though indicated, 23.1% of women were not treated with P2Y12 inhibitors (vs 14.2% of men; P 60%). Significantly higher in-hospital (5.4% vs 3.7%) and 1-year (8.2% vs 4.9%) mortality was observed among women compared to men, which was mainly attributed to cardiovascular causes. Conclusions Despite older age and unfavourable risk profile, female ACS patients seem to be suboptimally treated with P2Y12 inhibitors. To reduce mortality associated with ACS, improved prevention and optimized therapeutic approaches are needed.

INTRODUCTION: For a long time, vitamin K antagonists (VKA) were the only oral anticoagulation therapy available to reduce adverse events in atrial fibrillation (AF) patients. Direct-acting oral anticoagulants (DOAC) are at least as effective and safe as VKA with few drug interactions, rapid onset, and short half-life. Four DOACs, dabigatran, apixaban, rivaroxaban, and edoxaban, have demonstrated efficacy and safety for treatment in AF patients.AREAS COVERED: The purpose of this review article is to analyze the current evidence in clinical trials and in real-world populations and performed a new analysis with the estimated effect of those DOACs over the VKA population from the FANTASIIA registry.EXPERT OPINION: In the absence of randomized, controlled head-to-head comparisons between DOACs, high-quality observational data can provide useful information on the comparative effectiveness of DOACs. Current clinical guidelines recommend the management of oral anticoagulation in AF patients with DOACs over VKA for stroke prevention; however, many guidelines generally do not suggest a specific DOAC choice in clinical practice. The revised evidence in this manuscript and our real experience reflects that apixaban and dabigatran show the best efficacy and safety profile.

The 2020 ESC atrial fibrillation (AF) guidelines suggest the novel 4S-AF scheme for the characterization of AF. Imaging techniques could be helpful for this objective in everyday clinical practice, and information derived from these techniques reflects basic aspects of the pathophysiology of AF, which may facilitate treatment decision-making, and optimal management of AF patients. The aim of this review is to provide an overview of the mechanisms associated with atrial fibrosis and to describe imaging techniques that may help the management of AF patients in clinical practice. Transthoracic echocardiography is the most common procedure given its versatility, safety, and simplicity. Transesophageal echocardiography provides higher resolution exploration, and speckle tracking echocardiography can provide incremental functional and prognostic information over conventional echocardiographic parameters. In addition, LA deformation imaging, including LA strain and strain rate, are related to the extent of fibrosis. On the other hand, multidetector-row computed tomography and cardiac magnetic resonance provide higher resolution data and more accurate assessment of the dimensions, structure, and spatial relationships of the LA. Imaging is central when deciding on catheter ablation or cardioversion, and helps in selecting those patients who will really benefit from these procedures. Moreover, imaging enhances the understanding of the underlying mechanisms of atrial remodeling and might assists in refining the risk of stroke, which help to select the best medical therapies/interventions. In summary, evaluation of LA enlargement, LA remodeling and fibrosis with imaging techniques adds clinical and prognostic information and should be assessed as a part of routine comprehensive AF evaluation.

Background: The use of rapid deployment and sutureless aortic prostheses is increasing. Previous reports have shown promising results on haemodynamic performance and mortality rates. However, the impact of these bioprostheses on left ventricular mass (LVM) regression remains unknown. We decided to study the changes in remodelling and LVM regression in isolated severe aortic stenosis treated with conventional or Perceval® or Intuity® valves. Method and Results: From January 2011 to January 2016, 324 bioprostheses were implanted in our centre. The collected characteristics were divided into 3 groups: conventional valves, Perceval®, and Intuity®, and they were analysed after 12 months. There were 183 conventional valves (56%), 72 Perceval® (22%), and 69 Intuity® (21.2%). The statistical analysis showed significant differences in transprosthetic postoperative peak gradient (23 [18–29] mm Hg vs. 21 [16–29] mm Hg and 18 [14–24] mm Hg, p < 0.001), ventricular mass electrical criteria regression (Sokolow and Cornell products), and 1-year survival (90 vs. 93% and 97%, log rank p value = 0.04) in conventional, Perceval®, and Intuity® groups. Conclusions: We observed differences in haemodynamic, electrocardiographic, and echocardiographic parameters related to the different types of prosthesis. Patients with the Intuity® prosthesis had the highest reduction in peak aortic gradient and the higher ventricular mass regression. Besides, patients with the Intuity® prosthesis had less risk of mortality during follow-up than the other two groups. Further studies are needed to confirm these findings.

The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy. Full English text available from: www.revespcardiol.org/en

Introduction: Oral anticoagulants (OAC) reduce stroke/systemic embolism and mortality risks in atrial fibrillation (AF). However, there is an inherent bleeding risk with OAC, where intracranial hemorrhage (ICH) is the most feared, disabling, and lethal complication of this therapy. Therefore, the optimal management of OAC-associated ICH is not well defined despite multiple suggested strategies. Areas covered: In this review, the authors describe the severity and risk factors for OAC-associated ICH and the associated implications for using DOACs in AF patients. We also provide an overview of the management of OAC-associated ICH and treatment reversal strategies, including specific and nonspecific reversal agents as well as a comprehensive summary of the evidence about the resumption of DOAC and the optimal timing. Expert opinion: In the setting of an ICH, supportive care/measures are needed, and reversal of anticoagulation with specific agents (including administration of vitamin K, prothrombin complex concentrates, idarucizumab and andexanet alfa) should be considered. Most patients will likely benefit from restarting anticoagulation after an ICH and permanently withdrawn of OAC is associated with worse clinical outcomes. Although the timing of OAC resumption is still under debate, reintroduction after 4–8 weeks of the bleeding event may be possible, after a multidisciplinary approach to decision-making.

Resumen Introduccion y objetivos Comparar los resultados a largo plazo de los anticoagulantes orales directos (ACOD) frente a los antagonistas de la vitamina K (AVK) en pacientes del mundo real con fibrilacion auricular no valvular (FANV) en un estudio nacional prospectivo. Metodos El estudio FANTASIIA incluyo consecutivamente a pacientes ambulatorios con FANV anticoagulados con ACOD o AVK desde junio de 2013 hasta octubre de 2014. Se compararon las tasas de eventos segun el anticoagulante administrado. Resultados Se incluyo a 2.178 pacientes (edad, 73,8 ± 9,4 anos; el 43,8% mujeres); de ellos, 533 (24,5%) recibian ACOD y 1.645 (75,5%), AVK. Tras una mediana de seguimiento de 32,4 meses, los pacientes con ACOD tuvieron tasas mas bajas de ictus —0,40 (IC95%, 0,17-0,97) frente a 1,07 (IC95%, 0,79-1,46) pacientes/ano; p = 0,032—, hemorragias mayores —2,13 (IC95%, 1,45-3,13) frente a 3,28 (IC95%, 2,75-3,93) pacientes/ano; p = 0,044—, muerte cardiovascular —1,20 (IC95%, 0,72-1,99) frente a 2,45 (IC95%, 2,00-3,00) pacientes/ano; p = 0,009— y muerte total —3,77 (IC95%, 2,83-5,01) frente a 5,54 (IC95%, 4,83-6,34) pacientes/ano; p = 0,016—. En el analisis de Cox modificado segun el metodo de Andersen-Gill para datos con multiples eventos, las razones de riesgos instantaneos para los pacientes con ACOD fueron 0,42 (0,16-1,07) para el ictus; 0,47 (0,20-1,16) para la embolia sistemica en general; 0,76 (0,50-1,15) para las hemorragias mayores; 0,67 (0,39-1,18) para la muerte cardiovascular; 0,86 (0,62-1,19) para la mortalidad total y 0,82 (0,64-1,05) para el combinado de ictus, embolias, hemorragias mayores y muerte. Conclusiones El tratamiento con ACOD se asocia con una tendencia a una menor tasa de todos los eventos graves, incluida la mortalidad, en relacion con los AVK en pacientes con FANV en Espana.

We investigated the impact of diabetes mellitus (DM) in acute coronary syndrome (ACS) patients, and the 2-year prognosis based on antiplatelet therapy.This is a prospective and multicenter registry including hospitalized ACS patients. Clinical management and antiplatelet therapy at discharge were recorded. Bleeding events, all-cause mortality and major adverse cardiovascular events (MACEs) were recorded during 2-years and compared according to DM and the P2YFrom 1717 ACS patients, 653 (38%) had DM. Diabetic patients were older, more commonly females, with higher prevalence of comorbidities and more conservative management. After excluding antiplatelet monotherapy or oral anticoagulation, clopidogrel was prescribed in 59.6% of DM patients. Cox regression analysis showed that DM was an independent risk factor for MACE (aHR 1.39, 95% CI 1.05-1.83). The use of clopidogrel instead of ticagrelor/prasugrel was also independently associated with MACE (aHR 1.71, 95% CI 1.11-2.63), and all-cause mortality (aHR 2.47, 95% CI 1.23-4.96) in diabetic patients (log-rank p-values 0.001).In ACS patients, DM was associated with higher risk of MACE. In such patients, the use of ticagrelor/prasugrel reduced MACE and mortality compared to clopidogrel. Novel P2Y

BACKGROUND: Multimorbidity is common in atrial fibrillation (AF) patients. Charlson comorbidity index (CCI) is used to evaluate multimorbidity in the general population. Limited long-term data are available on the relationship between CCI and AF. We examined the association between CCI, anticoagulation control and outcomes in AF patients.METHODS: We studied 1956 from the FANTASIIA registry, an observational Spanish nationwide study on anticoagulated AF patients. Time in therapeutic range (TTR) was used to evaluate anticoagulation control. Stroke/TIA, major bleeding, cardiovascular (CV) death and all-cause death were study outcomes.RESULTS: Mean ± SD CCI was 1.1 ± 1.2. Based on CCI quartiles, patients were categorised in four groups: 676 (34.6%) in Q1 (CCI 0); 683 (34.9%) in Q2 (CCI 1); 345 (17.6%) in Q3 (CCI 2); and 252 (12.9%) in Q4 (CCI ≥3). In vitamin K antagonist treated patients, the highest CCI quartile was inversely associated with TTR >70% (odds ratio:0.67, 95% confidence interval (CI):0.45-0.99). During observation, a progressively higher rate of major bleeding, CV death and all-cause death was found across the quartiles (all p < 0.001). The final Cox multivariable regression analysis showed an association with increasing risk for major bleeding occurrence in Q3 and Q4 (hazard ratio (HR):1.69, 95%CI:1.00-2.87 and HR:1.92, 95%CI:1.08-3.41). An increasing risk for all-cause death and CV death was found across CCI quartiles.CONCLUSIONS: In a nationwide contemporary cohort of AF anticoagulated patients, multimorbidity was inversely associated with good anticoagulation control. A progressively higher risk for major bleeding, CV death and all-cause death was found across CCI quartiles.

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.

In cardiovascular disease (CVD), biomarkers (i.e., “biological markers”) could have multiple roles in understanding the complexity of cardiovascular (CV) pathophysiology and to offer an integrated approach to management. Biomarkers could help in daily practice as a diagnostic tool, to monitor therapy response, to assess prognosis and as early marker of CV damage, or to stratify risk. In recent years, the role of biomarkers in CVD is even more relevant and some have recently been included in clinical management guideline recommendations. The aim of this review is to discuss the recommendations in clinical guidelines of various biomarkers and to review their usefulness in daily clinical practice. Ultimately, a balance is needed between simplicity and practicality for clinical decision-making. Most biomarkers (whether blood, urine, or imaging-based) will improve on clinical risk stratification, but awaiting biomarker results may lead to delays in the initiation of therapy, for example, anticoagulation for stroke prevention in atrial fibrillation. Many biomarkers are nonspecific, being predictive of many CV and non-CV outcomes, so would be better as “rule-out” rather than “rule-in” assessments. Derivation of some biomarkers have also been made in highly selected clinical trial cohorts, where measurement is made at baseline but outcomes determined many years later; given the dynamic nature of risk in the “real world” where patients get older and develop incident risk factors, this may give a false impression of the risk profile. Finally, some laboratory biomarkers have a diurnal variation and inter-/intravariability (and lower limits of detection) in assays, which may be expensive, are added considerations.

Dual antiplatelet therapy is one of the main treatments in acute coronary syndrome (ACS). Switching antiplatelet agents may be necessary in some patients to improve efficacy or safety. The objective of this study was to determine the prevalence, predictors, and implications of clinical switching in patients during hospital admission and 1-year follow-up at discharge. Observational, prospective, multicenter registry study in patients discharged following an admission for ACS and followed up for 1 year. We analyzed ischemic and bleeding events as well as treatment changes. We recruited 1717 patients; in-hospital switching occurred in 425 (24.8%): 15.1% to clopidogrel and 84.9% to newer antiplatelet drugs (prasugrel or ticagrelor). Those switched to newer antiplatelets were younger, with lower scores on the GRACE and CRUSADE scales, admitted more frequently for ST-elevation myocardial infarction and underwent more invasive management and percutaneous revascularization. The clinical cardiologist was responsible for most in-hospital switching to newer antiplatelets (79.6%). The loading dose of the second antiplatelet did not affect incidence of bleeding events. Post-discharge switching was infrequent (2%) and depended mainly on clinical indications; only 30% was related to a new ACS. In a contemporary registry with ACS, in-hospital switching of antiplatelet drugs was frequent. Those switched to newer antiplatelets were younger and admitted more frequently for ST-elevation myocardial infarction. Post-discharge switching was infrequent.

Resumen La fibrilacion auricular es la arritmia cardiaca mas prevalente en la poblacion general y su presencia aumenta 5 veces el riesgo de que se produzcan fenomenos tromboembolicos. El tratamiento antitrombotico disminuye ese riesgo; sin embargo, aumenta la posibilidad de fenomenos hemorragicos, de los que la hemorragia intracraneal es la complicacion mas temida. El riesgo no es homogeneo en todos los pacientes, por lo cual en los ultimos anos se han desarrollado diferentes escalas de riesgo tromboembolico (las escalas CHADS2, CHA2DS2-VASc y ATRIA); de ellas, la escala CHA2DS2-VASc es la recomendada por las guias de practica clinica para optimizar el tratamiento antitrombotico de los pacientes con fibrilacion auricular. Las mismas guias recomiendan valorar no solo el riesgo trombotico, sino tambien el hemorragico. Se han propuesto distintos esquemas de riesgo que valoran el riesgo hemorragico del paciente (HEMORR2HAGES, HAS-BLED, ATRIA y ORBIT-AF), pero actualmente no se recomienda ninguno de forma explicita en la guia de practica clinica de la Sociedad Europea de Cardiologia. Es fundamental evaluar el beneficio clinico neto del tratamiento anticoagulante, en el cual el beneficio esperado con el tratamiento anticoagulante excede el dano esperado por una posible hemorragia. Informacion sobre el suplemento: este articulo forma parte del suplemento titulado «Actualizacion en el tratamiento de los pacientes con fibrilacion auricular sometidos a intervencion coronaria», que ha sido patrocinado por Boehringer Ingelheim.

Background: There is scarce information on the prognostic role of frailty and Atrial Fibrillation (AF) in elderly patients Acute Coronary Syndrome (ACS). Methods: The aim was to analyse the management of elderly patients with frailty and AF who suffered an ACS using data of the prospective multicentre LONGEVO-SCA registry. We evaluated the predictive performance of FRAIL, Charlson scores and AF status for adverse events at 6 months follow-up. Results: A total of 531 unselected patients with ACS and above 80 years old [mean age 84.4 (SD=3.6) years; 322 (60.6%) male] were enrolled, of whom 128 (24.1%) with AF and 145 (27.3%) with frailty. Mutually exclusive number of patients were as follows: non-Frail and sinus rhythm (SR) 304 (57.2%); Frail and SR 99 (18.6%); non-Frail and AF 82 (15.4%); Frail and AF 46 (8.7%). Frail and AF patients compared with non-frail and SR patients had higher risk of all-cause mortality [HR 2.61, (95%CI 1.28-5.31; p=0.008)], readmissions [HR 2.28, (95%CI 1.37-3.80); p=0.002)] and its composite [HR 2.28, (95%CI 1.44-3.60); p

Background Evaluation of thromboembolic risk is essential in anticoagulated atrial fibrillation (AF) patients. The CHA2DS2-VASc score is largely validated and recommended by most guidelines. The GARFIELD-AF Stroke score has been proposed as an alternative risk score. Methods We analyzed warfarin-treated patients from SPORTIF III and V studies. Any thromboembolic event (TE) was an adjudicated study outcome. We compared the two scores' capacity in predicting any TE occurrence. Results A total of 3,665 patients (median [interquartile range] age: 72 [66–77] years; 30.5% female) were included in this analysis. After a mean (standard deviation) follow-up of 566.3 (142.5) days, 148 (4.03%) TEs were recorded. Both continuous CHA2DS2-VASc and GARFIELD-AF were associated with TE (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.22–1.53 and HR: 2.43, 95% CI: 1.72–3.42), with modest predictive ability (c-indexes: 0.63, 95% CI: 0.59–0.68 and 0.61, 95% CI: 0.56–0.66, respectively), with no differences. CHA2DS2-VASc quartiles showed an increasing cumulative risk, while in GARFIELD-AF only the highest quartile (Q4) demonstrated an increased TE risk. On multivariate Cox regression analysis, CHA2DS2-VASc quartiles were associated with increasing risk of TE, whereas for GARFIELD-AF only Q4 showed an association with TE. Discrimination analysis showed that GARFIELD-AF quartiles were associated with a 48.7% reduction in discriminatory ability. Using decision curve analysis, CHA2DS2-VASc was associated with improved clinical usefulness and net clinical benefit, compared with GARFIELD-AF. Conclusion In a warfarin-treated trial cohort of AF patients, both CHA2DS2-VASc and GARFIELD-AF Stroke scores were associated with adjudicated TE events, with modest predictive capacity. The simpler CHA2DS2-VASc score improved discriminatory capacity compared with the more complex GARFIELD-AF score, demonstrating improved clinical usefulness and net clinical benefit.

BACKGROUND: Nurses play a central role in the management of atrial fibrillation (AF) patients. An unresolved question is whether a nurse-led clinic would improve clinical outcomes. Herein, we investigated the impact of a nurse-led clinic on anticoagulation therapy and clinical outcomes in a cohort of naïve AF patients.METHODS: Prospective study including AF patients starting vitamin K antagonists (VKAs) into a nurse-led AF clinic. These patients were followed in this specific AF clinic. Additionally, AF patients already taking VKAs for 6 months followed according to the routine clinical practice were included as comparison group. The quality of anticoagulation was assessed at 6 months. Efficacy and safety endpoints were recorded during follow-up.RESULTS: We included 223 patients (Nurse-led clinic: 107; Usual care: 116). The mean time in therapeutic range and the proportion of INRs within the therapeutic range were similar in both groups. During 2.06 (IQR 1.01-2.94) years of follow-up, 64 (28.7%) patients changed to direct-acting oral anticoagulants. The proportion of switchers was higher in the nurse-led clinic (37.4%) than in the usual care group (20.7%) (P = .006) and these patients spent less time to switch (2.0 [IQR 0.7-2.9] vs 6.0 [IQR 3.7-11.2] years; P < .001). Importantly, the annual rate of ischaemic stroke/TIA was significantly lower in the nurse-led clinic (0.47%/year vs 3.88%/year, P = .016), without differences in safety endpoints.CONCLUSION: A nurse-led AF clinic may offer a "patient-centered" review and holistic follow-up, and it would be associated with a reduction of ischaemic stroke/TIA, without increasing bleeding complications. Further studies should confirm these results.

Observational study [Abstract] Background: Atrial fibrillation (AF) and peripheral artery disease (PAD) are common conditions that increase cardiovascular risk. We determined the association between PAD and prognosis in a cohort of real-world patients receiving oral anticoagulant therapy for nonvalvular AF. Methods: We prospectively included 1956 patients (mean age 73.8 ± 9.5 years, 44.0% women) receiving oral anticoagulant therapy for AF. Clinical characteristics were collected at baseline. Patients were followed for a period of 3 years. Survival analysis and multivariable regression analyses were performed to assess variables related to death, stroke, bleeding, myocardial infarction and major adverse cardiovascular events (MACE). Results: Patients with PAD (n = 118; 6%) exhibited higher rates of cardiovascular risk factors and cardiovascular diseases. After 3 years of follow-up, there were a total of 255 deaths (no PAD 233, vs PAD 22), 45 strokes (43 vs 2), 146 major bleedings (136 vs 10) and 168 MACE (148 vs 20). On univariate analysis, there was a higher risk of cardiovascular mortality (2.02%/year no PAD vs 4.08%/year PAD, P = .02), myocardial infarction (0.99%/year no PAD vs 2.43%/year PAD, P = .02) and MACE (3.18%/year no PAD vs 6.99%/year PAD, P < .01). There was no statistically significant association with these events after multivariable adjustment. Conclusions: In a large cohort of anticoagulated patients with AF, the presence of PAD represents a higher risk subgroup and is associated with worse crude outcomes. The exact contribution of the PAD independently of other cardiovascular diseases or risk factors requires further investigation. Instituto de Salud Carlos III; RD16/11/00420 Instituto de Salud Carlos III; RD12/0042/0068 Instituto de Salud Carlos III; RD12/0042/0010 Instituto de Salud Carlos III; RD12/0042/0069 Instituto de Salud Carlos III; RD12/0042/0063

[Resumen] Introducción y objetivos. La fibrilación auricular tiene un mal pronóstico asociado fundamentalmente al desarrollo de ictus. A pesar del uso de anticoagulantes, algunos pacientes pueden sufrir ictus y también hemorragias graves. El tratamiento con antagonistas de la vitamina K (AVK) se controla mediante la razón internacional normalizada (INR). Nuestro objetivo fue estudiar la incidencia de ictus y hemorragias mayores, e investigar los valores de la INR y el tiempo en rango terapéutico en los 6 meses previos durante dichos episodios en pacientes con fibrilación auricular tratados con AVK. Métodos. Se incluyeron 1.483 pacientes con fibrilación auricular tratados con AVK durante al menos los 6 meses previos, incluidos consecutivamente desde junio de 2013 hasta octubre de 2014, con una mediana de seguimiento de 32,4 meses. Se identificaron aquellos pacientes que ingresaron por ictus o hemorragia mayor y se determinó la INR en cada episodio. Resultados. Se registraron 40 ictus (1,07/100 pacientes/año) y 120 hemorragias mayores (3,28/100 pacientes/año). La INR durante los ictus fue 2,33 ± 0,59, y durante las hemorragias 3,17 ± 1,48. El 57,5% de los pacientes tenían una INR de 2-3 durante los ictus y el 48,3% durante las hemorragias. Los pacientes que sufrieron un ictus con una INR fuera de rango durante el episodio presentaron un tiempo en rango terapéutico más bajo que aquellos con la INR en rango (49,2 ± 20,8% frente a 68,8 ± 19,4%; p = 0,043). Conclusiones. La mitad de los ictus y hemorragias mayores se producen con valores de la INR «adecuados» (2 a 3). Cambios en la estrategia de anticoagulación pueden ser necesarios para disminuir esta elevada tasa de eventos. [Abstract] Introduction and objectives. Atrial fibrillation has a poor prognosis, mainly due to the occurrence of cardioembolic stroke. Despite the use of anticoagulants some patients can develop stroke as well as severe bleeding. Treatment with vitamin K antagonists is usually controlled by means of the international normalized ratio (INR). The aim of this study was to investigate the incidence of stroke and major bleedings, as well the values of INR and the time in therapeutic range within the previous 6 months during these events. Methods. The study included 1483 patients with atrial fibrillation treated with vitamin K antagonists for at least 6 months prior to inclusion, consecutively recruited from June 2013 to October 2014, with a median follow-up of 32.4 months. Those patients admitted due to an episode of stroke or severe bleeding were identified, and an analysis was performed on the INR values obtained for each episode. Results. There was a total of 40 strokes (1.07/100 patients/year) and 120 severe bleedings (3.28/100 patients/year) during the study period. The mean INR value during stroke episodes was 2.33 ± 0.59, and during severe bleeding 3.17 ± 1.48, with 57.5% of patients having had an INR of 2-3 during strokes, and 48.3% during bleedings. Patients with an INR out of range during the stroke had a time in therapeutic range lower than those with an INR between 2 and 3 during the event (49.2 ± 20.8% vs. 68.8 ± 19.4%; P = .043). Conclusions. More than 50% of strokes and almost 50% of severe bleedings occur with ‘adequate’ (2 to 3) INR values. Changes in the anticoagulation strategy seem to be necessary to decrease this high rate of severe events.

BACKGROUND:Atrial fibrillation (AF) patients with diabetes (DM) are at increased risk of cardiovascular events and have higher related morbidity and mortality. PURPOSE:To compare clinical characteristics, cardiovascular adverse outcomes and quality of anticoagulation in AF patients with and without DM. METHODS:AF patients from the Spanish national, multicentric, prospective FANTASIIA registry were included. Patients received oral anticoagulation (vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC)) for at least 6 months before inclusion. Baseline clinical characteristics and comorbidities were recorded. After 2-years follow-up, the association between adverse events and the presence of DM was evaluated. RESULTS:1956 individuals (mean age 73.8 ± 9.5 years, 56% male) were analysed; of these, 574 (29.3%) had DM. Diabetic patients had increased prevalence of other risk factors such as hypertension (90.6% vs 76.1%; p

The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy.

Background Prasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long-term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y(12) inhibitors in current clinical practice patients discharged afterACS. Methods We collected data from the ACHILLES registry, and an observational, prospective and multicentre registry of patients discharged after ACS. We analysed baseline characteristics, clinical profile and therapy during ACS admission and compared with the different treatments at discharge. After 1 year of follow-up, ischaemic and major bleeding events were analysed. Multivariate Cox regression analysis and Kaplan Meier curves were also plotted. Results Of 1717 consecutive patients, 1294 (75.4%) were discharged with a P2Y12 inhibitor without oral anticoagulation. Novel oral P2Y(12) inhibitors were indicated in 47%. Patients treated with clopidogrel were elderly (69.1 +/- 13.4 vs 60.4 +/- 11.5 years; P < .001) and had a higher prevalence of cardiovascular risk factors. GRACE and CRUSADE scores were higher in the clopidogrel than in novel oral P2Y(12) inhibitors group (P < .001). After 1 year of follow-up, 64(5.0%/year) patients had a new myocardial infarction, 127(10.0%/year) had a major adverse cardiovascular event (MACE) and 78(6.1%/year) died. Patients treated with clopidogrel had a significantly higher annual rate of cardiovascular mortality, MACE and all-cause mortality (allP < .001) without differences in major bleeding (P = .587) compared with novel oral P2Y(12) inhibitors. After multivariate adjustment for the main clinical variables related to adverse prognosis in ACS patients, the discharge with novel oral P2Y(12) inhibitors therapy was independently associated with lower risk of all-cause mortality (HR0.49, 95% CI [0.24-0.98], P = .044) and lower risk of MACE (HR0.64, 95% CI [0.41-0.98], P = .044). Conclusions In this prospective, observational and current clinical practice ACS registry, the use of novel oral P2Y(12) inhibitors was associated with a reduction in adverse events compared with clopidogrel in patients with ACS. Novel oral P2Y(12) inhibitors prescription at discharge was independently associated with lower all-cause mortality and MACE without differences in bleeding events. However, clopidogrel remained the most common P2Y12 inhibitor employed for ACS, especially in older and high-risk patients.

Objective: To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Methods: A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, observational, multicenter study. Basal features, embolic events (stroke and systemic embolism), severe bleedings, and all-cause mortality at follow up were investigated according to the anticoagulant treatment received. Results: Mean age was 84.0 ± 3.4 years, 56% were women. Direct oral anticoagulants were prescribed to 123 (21.3%) patients. Compared with 455 (78.7%) patients treated with VKAs, those treated with DOACs presented a lower frequency of permanent AF (52.9% vs 61.6%, P = .01), cancer history (4.9% vs 10.9%, P = .046), renal failure (21.1% vs 32.2%, P = .02), and left ventricular dysfunction (2.4% vs 8.0%, P = .03); and higher frequency of previous stroke (26.0% vs 16.6%, P = .02) and previous major bleeding (8.1% vs 3.6%, P = .03). There were no significant differences in Charlson, CHA2DS2VASc, nor HAS-BLED scores. At 3-year follow up, rates of embolic events, severe bleedings, and all-cause death (per 100 patients-year) were similar in both groups (DOACs vs VKAs): 0.34 vs 1.35 ( P = .15), 3.45 vs 4.41 ( P = .48), and 8.2 vs 11.0 ( P = .18), respectively, without significant differences after multivariate analysis (hazard ratio [HR]: 0.25, 95% confidence interval [CI]: 0.03-1.93, P = .19; HR: 0.88, 95% CI: 0.44-1.76, P = .72 and HR: 0.84, 95% CI: 0.53-1.33, P = .46, respectively). Conclusion: In this “real-world” registry, the differences in major events rates in octogenarians with AF were not statistically significant in those treated with DOACs versus VKAs.

[Abstract] Background: While many risk factors for Atrial Fibrillation (AF) have been identified, there are important differences in their relative impact between sexes. The aim of our study was to investigate the influence of sex as a long-term predictor of adverse events in “real world” AF patients treated with direct oral anticoagulants. Methods: The FANTASIIA registry is a prospective, national and multicentric study including outpatients with anticoagulated AF patients. Baseline characteristics and adverse events at 3 years of follow-up were collected and classified by sex. Cox multivariate analysis was performed to investigate the role of sex in major events and composite outcomes. Results: A total of 1956 patients were included in the study. 43.9% of them were women, with a mean age of 73.8 ± 9.4 years (women were older 76.5 ± 7.9 vs 71.7 ± 10.1, p

BACKGROUND The clinical effect of peri-operative bridging therapy in atrial fibrillation (AF) patients remains unclear given that it may increase bleeding risk without providing significant benefits. We aimed to investigate peri-procedural events in relation to peri-operative use of bridging therapy in AF patients under Vitamin K Antagonists (VKAs). METHODS We included AF patients stable the previous 6 months on VKAs. During a median follow-up of 6.5 years (IQR 4.3-7.9), we recorded all invasive procedures and the peri-operative clinical management. All peri-procedural events (ischaemic stroke/transient ischaemic attack/systemic embolism, clinically relevant non-major bleeding and major bleeding) and severe peri-procedural events (ischaemic stroke/transient ischaemic attack/systemic embolism and major bleeding) suffered until the 30-days post-intervention period were recorded. RESULTS We included 1361 patients (48.7% male, median age 76 [IQR 71-81] years). There were 1100 (70.9%) procedures performed using bridging therapy. The rate of any (4.5% vs. 0.7%, P

Chronic kidney disease (CKD) is associated with worse clinical outcomes in patients with acute coronary syndrome. However, they are underrepresented in clinical trials. We aimed to investigate differences in prognosis of acute coronary syndrome patients with and without CKD, focusing on the use of novel P2Y12 receptor inhibitors. This multicenter registry involved patients with acute coronary syndrome from 3 tertiary institutions. After excluding anticoagulated patients and patients on antiplatelet monotherapy, 1280 patients remained. During 1 year of follow-up, we recorded all major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke), bleeds (Bleeding Academic Research Consortium classification) and deaths. Of 1280 patients, 325 (25.4%) had CKD; 55.5% of non-CKD patients and 22.7% of CKD patients were prescribed novel P2Y12 inhibitors. During follow-up, CKD patients under novel P2Y12 inhibitors showed a not statistically significant lower mortality and incidence of thrombotic events than clopidogrel-treated ones. In contrast, non-CKD patients taking novel P2Y12 inhibitors had better outcomes in terms of major adverse cardiovascular events (4.72 vs 9.41; P = .006), all-cause mortality (1.32 vs 4.24; P = .006), and severe bleeding events (Bleeding Academic Research Consortium 3-5) (0.94 vs 2.82; P = .030), without differences for any bleeding (8.11 vs 8.47; P = .849). Bleeding risk was not increased by using third-generation P2Y12 inhibitors in either group of patients. In conclusion, the use of third-generation P2Y12 inhibitors among non-CKD patients was associated with better outcomes. CKD patients receiving third-generation P2Y12 inhibitors treatment showed no statistically significant lower mortality and thrombotic events. Bleeding risk was not increased with the use of third-generation P2Y12 inhibitors in either group of patients.

IntroductionAtrial fibrillation (AF) is characterised by a high stroke risk. Vitamin K antagonists (VKAs) are the most commonly used oral anticoagulants (OACs) in Spain, but their efficacy and safety depend on the time in therapeutic range of International Normalized Ratio (INR) 2.0–3.0 over 65%–70%. Unfortunately, the difficulties of maintaining an optimal level of anticoagulation and the complications of VKAs (particularly haemorrhagic ones), frequently lead to cessation of this therapy, which has been associated with higher risk of adverse events (AEs), including ischaemic stroke. Our aims are as follows: (1) to evaluate the quality of oral anticoagulation with VKAs, the prevalence of poor quality of anticoagulation, and to identify factors predisposing to poor quality anticoagulation; and (2) to identify patients who will stop OAC and to investigate what factors influence the decision of OAC withdrawal.Methods and analysisProspective observational cohort study including outpatients newly diagnosed with AF and naïve for OACs from July 2016 to June 2018 in an anticoagulation clinic. Patients with prosthetic heart valves, rheumatic mitral valves or valvular AF will be excluded. Follow-up will extend for up to 3 years. During this period, the INR results and changes in the anticoagulant therapy will be recorded, as well as all AEs, or any other information that would be relevant to the proper conduct of research.Ethics and disseminationAll patients were informed about the nature and purpose of the study, and the protocol was approved by the Ethics Committee of Hospital General Universitario Morales Meseguer (reference: EST:20/16). This is an observational study focusing on ‘real life’ practice and therefore all treatments and follow-up will be performed in accordance to the routine clinical practice with no specific interventions or visits. The results of our study will be disseminated by presentations at national and international meetings, and publications in peer-reviewed journals.

Background Obesity and atrial fibrillation ( AF ) frequently coexist and independently increase mortality. We sought to assess the association between obesity and adverse events in patients receiving oral anticoagulants for AF . Methods and Results Consecutive AF outpatients receiving anticoagulant agents (both vitamin K antagonists and direct oral anticoagulants) were recruited into the FANTASIIA (Atrial fibrillation: influence of the level and type of anticoagulation on the incidence of ischemic and hemorrhagic stroke) registry. This observational, multicenter, and prospective registry of AF patients analyzes the quality of anticoagulation, incidence of events, and differences between oral anticoagulant therapies. We analyzed baseline patient characteristics according to body mass index, normal: 2 , overweight: 25–30 kg/m 2 , and obese: ≥30 kg/m 2 ), assessing all‐cause mortality, stroke, major bleeding and major adverse cardiovascular events (a composite of ischemic stroke, myocardial infarction, and total mortality) at 3 years’ follow‐up. In this secondary prespecified substudy, the association of weight on prognosis was evaluated. We recruited 1956 patients (56% men, mean age 73.8±9.4 years): 358 (18.3%) had normal body mass index, 871 (44.5%) were overweight, and 727 (37.2%) were obese. Obese patients were younger ( P P =0.42). After a median follow‐up of 1070 days, 255 patients died (13%), 45 had a stroke (2.3%), 146 a major bleeding episode (7.5%) and 168 a major adverse cardiovascular event (8.6%). Event rates were similar between groups for total mortality ( P =0.29), stroke ( P =0.90), major bleeding ( P =0.31), and major adverse cardiovascular events ( P =0.24). On multivariate Cox analysis, body mass index was not independently associated with all‐cause mortality, cardiovascular mortality, stroke, major bleeding, or major adverse cardiovascular events. Conclusions In this prospective cohort of patients anticoagulated for AF , obesity was highly prevalent and was associated with more comorbidities, but not with poor prognosis.

BACKGROUND: Soluble fibrin monomer complex (SFMC) is a biomarker of fibrin formation abnormally elevated in clinical situations of hypercoagulability.OBJECTIVE: We investigated the association and predictive performance of SFMC for stroke, adverse cardiovascular events, cardiovascular mortality and all-cause mortality in a cohort of patients with atrial fibrillation (AF) receiving vitamin K antagonist (VKA) anticoagulant therapy.DESIGN: During the second semester of 2007, we included 1226 AF outpatients stable on VKAs (INR 2.0-3.0) over a period of 6 months. SFMC levels were assessed at baseline. During 6.5 (IQR 4.4-8.0) years of follow-up, we recorded all ischemic strokes, adverse cardiovascular events (composite of stroke, acute heart failure, acute coronary syndrome and cardiovascular death), cardiovascular deaths and all-cause deaths.PARTICIPANTS: All patients were recruited consecutively. We excluded patients with rheumatic mitral valves, prosthetic heart valves, acute coronary syndrome, stroke, hemodynamic instability, hospital admissions or surgical interventions within the preceding 6 months.MAIN MEASURES: SFMC levels were measured in plasma by immunoturbidimetry in an automated coagulometer (STALiatestFM, Diagnostica Stago, Asnieres, France).KEY RESULTS: We recorded 121 (1.52%/year) ischemic strokes, 257 (3.23%/year) cardiovascular events, 67 (0.84%/year) cardiovascular deaths and 486 (6.10%/year) all-cause deaths. SFMC >12 μg/mL was not associated with stroke but was associated with higher risk of cardiovascular events (HR 1.72, 95% CI 1.31-2.26), cardiovascular mortality (HR 2.16, 95% CI 1.30-3.57) and all-cause mortality (HR 1.26, 95% CI 1.03-1.55). When SFMC >12 μg/mL was added to the CHA2DS2-VASc, there were significant improvements in predictive performance, sensitivity and reclassification for adverse cardiovascular events (c-index: 0.645 vs. 0.660, p = 0.010; IDI = 0.013, p CONCLUSIONS: In AF patients taking VKAs, high SFMC levels were associated with the risk of adverse cardiovascular events, cardiovascular mortality and all-cause mortality. The addition of SFMC to the CHA2DS2-VASc score improved its predictive performance for these outcomes, but failed to show an improvement in clinical usefulness.

The TIMI-AF score was described to predict net clinical outcomes (NCOs) in atrial fibrillation (AF) patients receiving warfarin. However, this score derived from the ENGAGE AF-TIMI 48 trial, and no external validation exists in real world clinical practice. We tested the long-term predictive performance of the TIMI-AF score in comparison with CHA2DS2-VASc and HAS-BLED in a ‘real-world’ cohort of anticoagulated AF patients. Methods We included 1156 consecutive AF patients stable on vitamin K antagonist (INR 2.0-3.0) during 6 months. The baseline risk of NCOs (composite of stroke, life-threatening bleeding, or all-cause mortality) was calculated using the novel TIMI-AF score. During follow-up, all NCOs were recorded and the predictive performance and clinical usefulness of TIMI-AF was compared with CHA2DS2-VASc and HAS-BLED. Results During 6.5 years (IQR 4.3-7.9), there were 563 NCOs (7.49%/year). ‘Low-risk’ (6.07%/year) and ‘medium-risk’ (9.49%/year) patients defined by the TIMI-AF suffered more endpoints that low- and medium-risk patients of CHA2DS2-VASc and HAS-BLED (2.37%/year and 4.40%/year for low risk; 3.48%/year and 6.39%/year for medium risk, respectively). The predictive performance of TIMI-AF was not different from CHA2DS2-VASc (0.678 vs 0.677, P =.963) or HAS-BLED (0.644 vs 0.671, P =.054). Discrimination and reclassification did not show improvement of prediction using the TIMI-AF score, and decision curves analysis did not demonstrate higher net benefit. Conclusions In VKA-experienced AF patients, the TIMI-AF score has limited usefulness predicting NCOs over a long-term period of follow-up. This novel score was not superior to CHA2DS2-VASc and HAS-BLED identifying low-risk AF patients.

Background: Matrix metalloproteinase (MMP)-2 plays an important role in the remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated the differences of MMP-2 expression between LV and RV in response to nandrolone decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice, based on their structural, functional, and biochemical characteristics. Methods: Totally 28 male C57B1 mice (6 weeks old; 20-23 g) were divided into four groups, including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups. After respective treatments for 8 weeks, echocardiographic examination was used to assess the cardiac structure and function. Van Gieson stain was used to examine the fibrosis of LV and RV in response to different treatments, and Western blotting analysis was performed to explore different MMP-2 expressions between LV and RV in response to ND and/or ST. Analysis of variance was used for comparing the four groups. Results: At 8 weeks, right ventricular dimension/body weight in the ND group was larger than the other three groups (F = 7.12, P < 0.05) according to the echocardiographic examination. Fibrosis induced by ND administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2 expression of the ND group in RV was significantly greater than the control and NS groups in RV and the corresponding ND group in LV. Conclusion: The experimental data support the hypothesis that ND administration induces greater MMP-2 expression increase in RV compared to LV, leading to consequent RV dilation. Key words: Fibrosis; Matrix Metalloproteinase 2; Nandrolone Decanoate; Swimming Training

Intracardiac thrombus is a potentially life-threatening condition associated with atrial fibrillation (AF), with a high risk of embolic complications. Oral anticoagulation (OAC) therapy is the first-line treatment for its prevention or resolution. For many patients, traditional OAC treatment using vitamin K antagonists (VKAs; e.g., warfarin) is limited by several factors and the advent of non-VKA oral anticoagulants (NOACs), with improved efficacy and safety profiles, has provided additional treatment options. However, studies are limited in number and are mostly case reports or series, with only one published modest-size prospective multicenter cohort study for rivaroxaban. No randomized controlled trials have been performed. Given the available data thus far, albeit weak, NOACs offer a possible alternative to VKAs for treating intracardiac thrombi.