Imaging in atrial fibrillation: A way to assess atrial fibrosis and remodeling to assist decision-making.

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.

Impact of frailty and atrial fibrillation in elderly patients with acute coronary syndromes.

BACKGROUND: There is scarce information on the prognostic role of frailty and atrial fibrillation (AF) in elderly patients with 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-month 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%); and 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 = .008)], readmissions [HR 2.28, (95%CI 1.37-3.80); P = .002)] and its composite [HR 2.28, (95% CI 1.44-3.60); P < .001)]. After multivariate adjustment, FRAIL score [HR 1.41, (95% CI 1.02-1.97); P = .040] and Charlson index [HR 1.32, (95% CI 1.09-1.59); P = .003] were significantly associated with mortality. AF status was not independently related with adverse events. CONCLUSIONS: Frailty but not AF status was independently associated with follow-up adverse events. Frailty status and high Charlson index were independent conditions associated with adverse events during the follow-up. The impact of functional status has a bigger prognostic role over AF status in elderly patients with ACS.

Peripheral artery disease and clinical outcomes in patients with atrial fibrillation: A report from the FANTASIIA registry.

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.

Comparison of Aortic Gradient and Ventricular Mass after Valve Replacement for Aortic Stenosis with Rapid Deployment, Sutureless, and Conventional Bioprostheses.

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.

Antithrombotic Therapy in Patients with Peripheral Artery Disease: A Focused Review on Oral Anticoagulation.

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.

One-year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry.

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 P2Y12 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 P2Y12 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 P2Y12 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 P2Y12 inhibitors. After multivariate adjustment for the main clinical variables related to adverse prognosis in ACS patients, the discharge with novel oral P2Y12 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 P2Y12 inhibitors was associated with a reduction in adverse events compared with clopidogrel in patients with ACS. Novel oral P2Y12 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.

A nurse-led atrial fibrillation clinic: Impact on anticoagulation therapy and clinical outcomes.

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.

Refining Stroke and Bleeding Prediction in Atrial Fibrillation by Adding Consecutive Biomarkers to Clinical Risk Scores.

Background and Purpose- Current European guidelines for the management of atrial fibrillation suggest using biomarkers to refine the risk stratification process. However, it is unclear whether ≥2 biomarkers incrementally improve risk prediction beyond 1 biomarker alone. We investigated whether the predictive performance of CHA2DS2-VASc and HAS-BLED scores could be enhanced by incrementally adding consecutive different biomarkers in real-world atrial fibrillation patients taking vitamin K antagonists therapy. Methods- We included 940 atrial fibrillation patients stable on vitamin K antagonists (international normalized ratio, 2.0-3.0) for at least the previous 6 months. At inclusion, VWF (von Willebrand factor), high-sensitivity troponin T, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity IL (interleukin)-6, fibrin monomers, and BTP (ß-trace protein) concentrations were quantified. During follow-up, all adverse events were recorded, and biomarkers were added to CHA2DS2-VASc and HAS-BLED scores depending on the C index. Results- During 6.5 (4.3-7.9) years, there were 98 ischemic strokes (1.60% per year) and 172 major bleeds (1.60% per year). After the addition of biomarkers, the predictive performance of CHA2DS2-VASc was not significantly increased, although the model with 3 biomarkers (ie, NT-proBNP+BTP+VWF) showed a low gain in sensitivity (integrated discrimination improvement, 2.70%; P<0.001). The predictive performance of HAS-BLED was enhanced in all biomarker-based models, with the best prediction shown by the model with 3 biomarkers (ie, VWF+NT-proBNP+high-sensitivity IL-6; C index, 0.600 [95% CI, 0.561-0.625] versus 0.639 [95% CI, 0.607-0.669]; P=0.025). This model also confirmed an increased sensitivity (integrated discrimination improvement, 5.20%; P<0.001) and positive reclassification (net reclassification improvement, 19.20%; P=0.020). Conclusions- By adding consecutive biomarkers, the predictive ability of CHA2DS2-VASc for ischemic stroke was not increased, whereas the predictive ability of HAS-BLED for major bleeding was only slightly enhanced. The net benefit and clinical usefulness of the biomarker-based models were marginal in comparison to the original scores based on clinical factors.

Prediction of long-term net clinical outcomes using the TIMI-AF score: Comparison with CHA2DS2-VASc and HAS-BLED.

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.

Pharmacogenetics of vitamin K antagonists and bleeding risk prediction in atrial fibrillation.

BACKGROUND: Polymorphisms in the vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes increase the bleeding risk in anticoagulated atrial fibrillation (AF) patients. Here, we aimed to investigate whether VKORC1 and CYP2C9 polymorphisms improved the predictive performance for major bleeding using the HAS-BLED score. MATERIAL AND METHODS: We recruited 652 consecutive AF patients stable on vitamin K antagonist (INR 2.0-3.0) during at least the previous 6 months. A baseline venous blood sample was obtained for DNA extraction. We gave an extra point to the HAS-BLED score if the patient was a simultaneous carrier of the VKORC1 and CYP2C9 polymorphisms related to bleeding, and we called this modified score "GEN|HAS-BLED." During a median follow-up of 7.6 years (IQR 5.6-8.0), all major bleeding events were recorded. RESULTS: During follow-up, 106 (16.2%) patients experienced a major bleeding (2.81%/y; 42 intracranial haemorrhages and 44 gastrointestinal bleeding) and 24 (3.7%) died from major bleeding (0.48%/y). Cox regression analyses demonstrated a significant association between HAS-BLED or GEN|HAS-BLED and major bleeds, both as continuous or categorical scores. Comparison of receiver operating characteristic (ROC) curves shows that original HAS-BLED clinical score had better predictive ability than GEN|HAS-BLED (0.660, 95% CI 0.622-0.696 vs 0.645, 95% CI 0.607-0.682; P = .030). Discrimination and reclassification analyses showed that GEN|HAS-BLED did not improve sensitivity compared with the original score and even showed significant negative reclassification. CONCLUSION: Adding pharmacogenetic factors (ie polymorphisms of the VKORC1 and CYP2C9 genes) to the HAS-BLED score does not improve the prediction or discrimination performance for major bleeding.

Relation of quality of anticoagulation control with different management systems among patients with atrial fibrillation: Data from FANTASIIA Registry.

BACKGROUND: Anticoagulation control in patients with atrial fibrillation (AF) has a multidisciplinary approach although is usually managed by general practitioners (GP) or haematologists. The aim of our study was to assess the quality of anticoagulation control with vitamin K antagonists (VKAs) in relation to the responsible specialist in a "real-world" AF population. METHODS: We consecutively enrolled VKA anticoagulated patients included in the FANTASIIA Registry from 2013 to 2015. We analysed demographical, clinical characteristics and the quality of anticoagulation control according to the specialist responsible (ie GPs or haematologists). RESULTS: Data on 1584 patients were included (42.5% females, mean age 74.0 ± 9.4 years): 977 (61.7%) patients were controlled by GPs and 607 (38.3%) by haematologists. Patients managed by GPs had higher previous heart disease (53.2% vs 43.3%, P < .001), heart failure (32.9% vs 26.5%, P < .008) and dilated cardiomyopathy (15.2% vs 8.7%, P < .001) with better renal function (69.3 ± 24.7 vs 63.1 ± 21.4 mL/min, P < .001) compared to patients managed by haematologists. There was no difference between groups in the type of AF, CHA2 DS2 -VASc or HAS-BLED scores, but patients with electrical cardioversion were more prevalent in GP group. The overall mean time in therapeutic range (TTR) assessed by Rosendaal method was 61.5 ± 24.9%; 52.6% of patients had TTR<65% and 60% of patients had TTR<70%. TTR was significantly lower in patients controlled by haematologists than by GPs (63 ± 24.4 vs 59.2 ± 25.6, P < .005). CONCLUSIONS: About 60% of AF patients anticoagulated with VKAs had poor anticoagulation control (ie TTR<70%), and their management was only slightly better than when it is managed by general practitioners.

Soluble Fibrin Monomer Complex and Prediction of Cardiovascular Events in Atrial Fibrillation: The Observational Murcia Atrial Fibrillation Project.

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 < 0.001; NRI = 0.121, p < 0.001) and cardiovascular mortality (c-index: 0.661 vs. 0.691, p = 0.006; IDI = 0.009, p = 0.049; NRI = 0.217, p < 0.001), but decision curves demonstrated a similar net benefit and clinical usefulness. 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.

Quality of oral anticoagulation with vitamin K antagonists in 'real-world' patients with atrial fibrillation: a report from the prospective multicentre FANTASIIA registry.

Aims: The efficacy and safety of oral anticoagulation (OAC) using the vitamin K antagonists (VKA) are closely associated with the quality of anticoagulation, reflected by time in therapeutic range (TTR). The SAMe-TT2R2 is a risk score developed to predict the quality of anticoagulation control among VKA users. To analyse the quality of anticoagulation and its clinical determinants based on different methods in a prospective cohort of atrial fibrillation patients on VKA treatment participating in the multicentre Spanish observational registry FANTASIIA. Methods and results: Estimated TTR was calculated from Rosendaal, direct method, international normalized ratio variability, and NICE criteria. Time in therapeutic range values were compared for those patients with a SAMe-TT2R2 score 0-2 and >2. One thousand four hundred and seventy patients were analysed (56.4% male, mean age 74.1 ± 9.5 years). Mean TTR was 61.5 ± 25.1 with Rosendaal and 64.7 ± 24.2 with direct method. There was a high correlation between both methods (ρ = 0.805). The prevalence of poor anticoagulation control was 55%. Diabetes mellitus [odds ratio (OR) 1.38; P = 0.008], peripheral artery disease (PAD, OR 1.62; P = 0.048), and HAS-BLED (OR 1.13; P = 0.022) were independently associated with TTR < 70%. SAMe-TT2R2 score 0-2 had a higher mean TTR than patients with SAMe-TT2R2 >2 (P = 0.044), with a specificity of > 90% for predicting TTR < 70%. Patients with TTR < 70% had higher risk of events (21.7 vs. 16.8%; P = 0.021). Conclusion: In a multicentre prospective registry, 55% of AF patients had poor anticoagulation control with diabetes mellitus, PAD, and HAS-BLED being independently associated with TTR < 70%. A high SAMe-TT2R2 scores had a high specificity for predicting a TTR < 70% as an indicator of poor quality anticoagulation.

Comparison of the 2MACE and TIMI-AF Scores for Composite Clinical Outcomes in Anticoagulated Atrial Fibrillation Patients.

BACKGROUND: Two risk scores have been developed to predict composite outcomes in atrial fibrillation (AF): the 2MACE and TIMI-AF scores. The aim of this study was to compare the predictive ability of these scores in 2 separate warfarin-treated cohorts (one 'real world', one clinical trial) of AF patients.Methods and Results:The 2MACE and TIMI-AF scores were calculated in the 'real-world' ATHERO-AF cohort (n=907), and in the randomized controlled AMADEUS trial (n=2,265). Endpoints were major adverse cardiovascular events (MACEs), net clinical outcomes (NCO) and a combination of them, namely "clinically relevant events" (CREs). ROC curves showed similar predictive ability for MACE for 2MACE and TIMI-AF, in both the ATHERO-AF (0.698 vs. 0.688, respectively P=0.783) and AMADEUS (0.657 vs. 0.569, respectively P=0.057) cohorts. Similarly, the TIMI-AF showed a comparable c-index with 2MACE for NCOs in the ATHERO-AF (0.676 vs. 0.667, P=0.737), and AMADEUS (0.666 vs. 0.663, P=0.859) cohorts. No differences were found between the 2 scores for the prediction of CREs (0.675 vs. 0.684, P=0.740 in ATHERO-AF and 0.669 vs. 0.667, P=0.889 in AMADEUS for 2MACE and TIMI-AF, respectively). CONCLUSIONS: This study showed that the 2MACE and TIMI-AF scores had modest but significant predictive ability for composite outcomes in AF. The clinical usefulness of both scores was similar, but the 2MACE score may be simpler and easy to use.

Antiplatelet therapy combined with acenocoumarol in relation to major bleeding, ischaemic stroke and mortality.

BACKGROUND: Vascular disease is a frequent comorbidity in atrial fibrillation (AF) patients, resulting in concomitant use of antiplatelet therapy. In the present study, we investigated the incidence and risk of major bleeding, ischaemic stroke, and mortality in a cohort of AF patients taking acenocoumarol plus antiplatelet therapy, in comparison with AF patients taking only acenocoumarol monotherapy. METHODS: We consecutively included 1361 "real-world" AF patients stable for at least the previous 6 months on acenocoumarol (INR 2.0-3.0). The primary endpoint was major bleeding defined using the 2005 International Society on Thrombosis and Haemostasis (ISTH) criteria. As secondary endpoints, we analysed ischaemic strokes and all-cause mortality. During follow-up, all adverse events were recorded and compared within patients taking acenocoumarol plus antiplatelet therapy and patients taking only acenocoumarol. RESULTS: During 6.5 years (IQR 4.3-7.9) of follow-up, there were 250 (2.83%/year) bleeds, 130 (1.47%/year) ischaemic strokes and 511 (6.23%/year) deaths. After multivariate Cox regression analyses, combined antithrombotic therapy was associated with major bleeding (HR 1.40, 95% CI 1.01-1.94; P = .048), but not lower mortality (HR 0.95, 95% CI 0.75-1.21; P = .674) or ischaemic stroke (HR 1.45, 95% CI 0.97-2.17; P = .072). CONCLUSIONS: In AF patients, the risk of bleeding is higher when antiplatelet therapy is combined with acenocoumarol, but the risk of mortality and stroke was not significantly different from that of patients taking only acenocoumarol.

Is the ORBIT Bleeding Risk Score Superior to the HAS-BLED Score in Anticoagulated Atrial Fibrillation Patients?

BACKGROUND: Several bleeding risk scores have been validated in patients with atrial fibrillation (AF). The ORBIT score has been recently proposed as a simple score with the best ability to predict major bleeding. The present study aimed to test the hypothesis that the ORBIT score was superior to the HAS-BLED score for predicting major bleeding and death in "real world" anticoagulated AF patients. METHODS AND RESULTS: We analyzed the predictive performance for bleeding and death of 406 AF patients who underwent 571 electrical cardioversion procedures and 1,276 patients with permanent/persistent AF from the FANTASIIA registry. In the cardioversion population, 21 patients had major bleeding events and 26 patients died. The predictive performance for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.77 (95% CI 0.66-0.88) and 0.82 (95% CI 0.77-0.93), respectively; P=0.080). For the FANTASIIA population, 46 patients had major bleeding events and 50 patients died. The predictive performances for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.63 (95% CI 0.56-0.71) and 0.70 (95% CI 0.62-0.77), respectively; P=0.116). For death, the predictive performances of HAS-BLED and ORBIT were not significantly different in both populations. The ORBIT score categorized most patients as "low risk". CONCLUSIONS: Despite the original claims in its derivation paper, the ORBIT score was not superior to HAS-BLED for predicting major bleeding and death in a "real world" oral anticoagulated AF population. (Circ J 2016; 80: 2102-2108).

New Approaches to the Role of Thrombin in Acute Coronary Syndromes: Quo Vadis Bivalirudin, a Direct Thrombin Inhibitor?

The pathophysiology of acute coronary syndrome (ACS) involves platelet activation and thrombus formation after the rupture of atherosclerotic plaques. Thrombin is generated at the blood-plaque interface in association with cellular membranes on cells and platelets. Thrombin also amplifies the response to the tissue injury, coagulation and platelet response, so the treatment of ACS is based on the combined use of both antiplatelet (such as aspirin, clopidogrel, prasugrel and ticagrelor) and antithrombotic drugs (unfractionated heparin, enoxaparin, fondaparinux and bivalirudin). Bivalirudin competitively inhibits thrombin with high affinity, a predictable response from its linear pharmacokinetics and short action. However, a present remarkable controversy exists between the latest main Guidelines in Clinical Practice and the key trials evaluating the use of bivalirudin in ACS. The aim of this review is to update the development of bivalirudin, including pharmacological properties, obtained information from clinical trials evaluating efficacy and safety of bivalirudin in ACS; as well as the recommendations of clinical Guidelines.

Patients with atrial fibrillation and common exclusion criteria from clinical trials are at high risk of clinical events: the Murcia AF Project II (MAFP-II) cohort study.

BACKGROUND: Some clinical characteristics and comorbidities in atrial fibrillation (AF) patients are exclusion criteria in randomized clinical trials (RCTs) investigating oral anticoagulants (OAC). However, these conditions are present also in everyday clinical practice patients. We compared the risk of adverse clinical outcomes between patients with and without RCT exclusion criteria. METHODS: The Murcia AF Project II was an observational cohort study including AF outpatients starting vitamin K antagonists (VKAs) from July 2016 to June 2018. For the selection of the exclusion criteria, the four pivotal RCTs of direct-acting OAC (DOACs) were used as reference. During 2 years, all ischemic strokes/transient ischemic attacks, major adverse cardiovascular events (MACEs), major bleeds, and all-cause deaths were recorded. RESULTS: 1050 patients (51.5% female, median age 77 years) were included, of whom 368 (35%) met at least one exclusion criterion for RCTs. During follow-up, the incidence rate ratios for major bleeding, MACE and all-cause mortality were higher among patients with exclusion criteria (all p < 0.001). Patients fulfilling at least one exclusion criterion had increased risks of major bleeding (aHR 1.48; 95% CI 1.22-1.81; p < 0.001), MACE (aHR 1.51, 95% CI 1.10-2.09, p = 0.012), and mortality (aHR 3.22, 95% CI 2.32-4.48, p < 0.001), as well as a lower event-free survival (all log-rank p < 0.001). CONCLUSIONS: In this AF cohort taking VKAs, more than one-third had at least one RCT exclusion criteria, which translates into higher risk of major bleeding, MACE, and death. These observations should be considered when translating RCTs results to AF patients for a proper and a more patient-centered management.

Advances in the medical treatment and diagnosis of intracranial hemorrhage associated with oral anticoagulation.

INTRODUCTION: With the increasing prevalence of atrial fibrillation (AF), it entails expanding oral anticoagulants (OACs) use, carrying a higher risk of associated hemorrhagic events, including intracranial hemorrhage (ICH). Despite advances in OACs development with a better safety profile and reversal agent for these anticoagulants, there is still no consensus on the optimal management of patients with OACs-associated ICH. AREAS COVERED: In this review, the authors have carried out an exhaustive search on the advances in recent years. The authors provide an update on the management of ICH in anticoagulated patients, as well as an update on the latest evidence on anticoagulation resumption, recent therapeutic strategies, and investigational drugs that could play a role in the future. EXPERT OPINION: Following an ICH event in an anticoagulated patient, a comprehensive clinical evaluation is imperative. Anticoagulation should be promptly withdrawn and reversed. Once the patient is stabilized, a reintroduction of anticoagulation should be considered, typically within a timeframe of 4-8 weeks, if feasible. If re-anticoagulation is not possible, alternative options such as Left Atrial Appendage Occlusion are available.

Incidence and clinical impact of inappropriate periprocedural and perioperative management of antiplatelet therapy.

BACKGROUND AND AIMS: There is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in "real life" in Spain. METHODS: A prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy. RESULTS: We included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents. CONCLUSIONS: Despite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the "real world" remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic.