Publications by authors named "Vanessa Roldan"

183 Publications

Anticoagulant therapy in patients with congenital FXI deficiency.

Blood Adv 2021 10;5(20):4083-4086

Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Centro de Investigación Biomédica en Red de Enfermedades Raras, Murcia, Spain.

The bleeding phenotype of factor XI (FXI) deficiency is unpredictable. Bleeding is usually mild and mostly occurs after injury. Although FXI deficiency renders antithrombotic protection, some patients might eventually develop thrombosis or atrial fibrillation, requiring anticoagulant therapy. There is almost no evidence on the bleeding risk in this scenario. Our retrospective study of 269 white FXI-deficient subjects (1995-2021) identified 15 cases requiring anticoagulation. They harbored 8 different F11 variants, mainly in heterozygosis (1 case was homozygote), and had mild to moderate deficiency (FXI:C: 20% to 70%). Two subjects (13.3%) had bleeding history before anticoagulation. Atrial fibrillation was the main indication (12/15; 80%). Fourteen patients started therapy with vitamin K antagonists (VKA), but 4 subjects were on direct oral anticoagulants (DOACs) at the end of follow-up. Over >1000 months of anticoagulation, 2 mild bleeding episodes in 2 patients (13.3%, 95% confidence interval: 3.7% to 37.9%) were recorded. No major/fatal events were reported. "Pre-post" bleeding localization and severity did not change despite treatment. On VKA, drug dosing and management were also standard, unaltered by FXI deficiency. We provide the largest description of anticoagulant use in FXI deficiency, and the first cases receiving DOACs. Although further studies are needed, our observations suggest that moderate FXI deficiency does not interfere with anticoagulant management nor bleeding risk.
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http://dx.doi.org/10.1182/bloodadvances.2021005695DOI Listing
October 2021

Prediction of Residual Stroke Risk in Anticoagulated Patients with Atrial Fibrillation: mCARS.

J Clin Med 2021 Jul 29;10(15). Epub 2021 Jul 29.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool L7 8TX, UK.

Our ability to evaluate residual stroke risk despite anticoagulation in atrial fibrillation (AF) is currently lacking. The Calculator of Absolute Stroke Risk (CARS) has been proposed to predict 1-year absolute stroke risk in non-anticoagulated patients. We aimed to determine whether a modified CARS (mCARS) may be used to assess the residual stroke risk in anticoagulated AF patients from 'real-world' and 'clinical trial' cohorts. We studied patient-level data of anticoagulated AF patients from the real-world Murcia AF Project and AMADEUS clinical trial. Individual mCARS were estimated for each patient. None of the patients were treated with non-vitamin K antagonist oral anticoagulants. The predicted residual stroke risk was compared to actual stroke risk. 3503 patients were included (2205 [62.9%] clinical trial and 1298 [37.1%] real-world). There was wide variation of CARS for each category of CHADS-VASc score in both cohorts. Average predicted residual stroke risk by mCARS (1.8 ± 1.8%) was identical to actual stroke risk (1.8% [95% CI, 1.3-2.4]) in the clinical trial, and broadly similar in the real-world (2.1 ± 1.9% vs. 2.4% [95% CI, 1.6-3.4]). AUCs of mCARS for prediction of stroke events in the clinical trial and real-world were 0.678 (95% CI, 0.598-0.758) and 0.712 [95% CI, 0.618-0.805], respectively. mCARS was able to refine stroke risk estimation for each point of the CHADS-VASc score in both cohorts. Personalised residual 1-year absolute stroke risk in anticoagulated AF patients may be estimated using mCARS, thereby allowing an assessment of the absolute risk reduction of treatment and facilitating a patient-centred approach in the management of AF. Such identification of patients with high residual stroke risk could help target more aggressive interventions and follow-up.
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http://dx.doi.org/10.3390/jcm10153357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348193PMC
July 2021

Relationship between multimorbidity and outcomes in atrial fibrillation.

Exp Gerontol 2021 10 23;153:111482. Epub 2021 Jul 23.

Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, Murcia, Spain.

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.
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http://dx.doi.org/10.1016/j.exger.2021.111482DOI Listing
October 2021

Number needed to treat for net effect of anticoagulation in atrial fibrillation: Real-world vs. clinical-trial evidence.

Br J Clin Pharmacol 2021 Jun 30. Epub 2021 Jun 30.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.

Aims: The net benefit of oral anticoagulants (OACs) in atrial fibrillation (AF) is poorly understood. We aimed to determine the NNT for net effect (NNT ) using calculator of absolute stroke risk (CARS) in anticoagulated patients with AF in real-world and clinical trial cohorts.

Methods: Post-hoc analysis of patient-level data from the real-world Murcia AF Project and AMADEUS clinical trial. Baseline risk of stroke was determined using CARS. The risk of stroke and major bleeding events with OAC were determined using the number of respective events at 1-year. NNT was calculated as a reciprocal of the net effect of absolute risk reduction with OAC (NNT  = 1/(absolute risk reduction of stroke[ARR ] - absolute risk increase of major bleeding[ARI ])).

Results: In total, 3511 patients were included (1306 [37.2%] real-world patients and 2205 [62.8%] clinical trial participants). The absolute 1-year stroke risk was similar across both cohorts. In the real-world cohort, OAC was associated with a 4.0% ARR , 25 NNT , 1.0% ARI , 100 NNT and 34 NNT . In the clinical trial cohort, OAC was associated with a 3.8% ARR , 27 NNT , 1.6% ARI , 63 NNT and 46 NNT . In both cohorts, the NNT was significantly lower in patients with an excess stroke risk of ≥2% by CARS.

Conclusion: Overall, the NNT approach in AF incorporates information regarding baseline risk of stroke and major bleeding, and relative effects of OAC with the potential to include multiple additional outcomes and weighting of events based on their perceived effects by individual patients.
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http://dx.doi.org/10.1111/bcp.14961DOI Listing
June 2021

Gut Microbiota and the Quality of Oral Anticoagulation in Vitamin K Antagonists Users: A Review of Potential Implications.

J Clin Med 2021 Feb 11;10(4). Epub 2021 Feb 11.

Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain.

The efficacy and safety of vitamin K antagonists (VKAs) as oral anticoagulants (OACs) depend on the quality of anticoagulation control, as reflected by the mean time in therapeutic range (TTR). Several factors may be involved in poor TTR such as comorbidities, high inter-individual variability, interacting drugs, and non-adherence. Recent studies suggest that gut microbiota (GM) plays an important role in the pathogenesis of cardiovascular diseases, but the effect of the GM on anticoagulation control with VKAs is unknown. In the present review article, we propose different mechanisms by which the GM could have an impact on the quality of anticoagulation control in patients taking VKA therapy. We suggest that the potential effects of GM may be mediated first, by an indirect effect of metabolites produced by GM in the availability of VKAs drugs; second, by an effect of vitamin K-producing bacteria; and finally, by the structural modification of the molecules of VKAs. Future research will help confirm these hypotheses and may suggest profiles of bacterial signatures or microbial metabolites, to be used as biomarkers to predict the quality of anticoagulation. This could lead to the design of intervention strategies modulating gut microbiota, for example, by using probiotics.
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http://dx.doi.org/10.3390/jcm10040715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916955PMC
February 2021

Factor XI, much more than an innocent observer.

J Thromb Haemost 2020 12;18(12):3172-3173

Department of Hematology and Clinical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, Murcia, Spain.

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http://dx.doi.org/10.1111/jth.15093DOI Listing
December 2020

Outcomes in VKA-treated patients with atrial fibrillation and chronic kidney disease: Clinical trials vs 'real-world'.

Int J Clin Pract 2021 Apr 15;75(4):e13888. Epub 2020 Dec 15.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.

Background: Our objectives were to evaluate the risk of adverse events in a 'real-world' vs 'clinical trial' cohort of atrial fibrillation (AF) patients with chronic kidney disease (CKD).

Methods: We studied patient-level data for vitamin K antagonist-treated AF patients with a creatinine clearance <60 mL/min from the Murcia AF Project and AMADEUS trial. The study end-points were ischaemic stroke, major bleeding, all-cause mortality, myocardial infarction and intracranial haemorrhage.

Results: This study included 1,108 AF patients with CKD. The annual rate of the composite study outcome of ischaemic stroke, major bleeding and all-cause mortality was higher in the real-world (13.4%) vs AMADEUS (6.6%) cohort with an IRR of 2.04 (95% CI,1.34-3.09), P < .001. Individual annual rates of major bleeding, all-cause mortality and non-cardiovascular mortality were significantly greater in the real-world cohort. Similar findings were demonstrated even after multivariable adjustment, with the composite outcome HR of 2.85 (95% CI,1.74-4.66), P < .001. In a propensity score matched cohort, this risk remained significantly higher in the real-world cohort (IRR 2.95 [95% CI,1.03-10.28], P = .027), as did the risk of major bleeding and all-cause mortality.

Conclusion: Vitamin K antagonist-treated AF patients with CKD are exposed to significant annual rates of major adverse events including all-cause mortality. This risk may be under-appreciated in the idealised environment of randomised controlled trials.
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http://dx.doi.org/10.1111/ijcp.13888DOI Listing
April 2021

Pilot Study on the Role of Circulating miRNAs for the Improvement of the Predictive Ability of the 2MACE Score in Patients with Atrial Fibrillation.

J Clin Med 2020 Nov 12;9(11). Epub 2020 Nov 12.

Department of Hematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, Centro Regional de Hemodonación, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), 30003 Murcia, Spain.

. Atrial fibrillation (AF) increases the risk for stroke but also for non-stroke major adverse cardiovascular events (MACE). The 2MACE score was recently proposed to predict these events. Since the interest of microRNAs (miRNAs) in cardiovascular diseases is increasing, we aimed to investigate whether miRNA levels may improve the predictive performance of the 2MACE score. . We included consecutive AF patients stable on vitamin K antagonist therapy. Blood samples were drawn at baseline and plasma expression of miRNAs was assessed. During a median of 7.6 (interquartile range (IQR) 5.4-8.0) years, the occurrence of any MACE (nonfatal myocardial infarction/cardiac revascularization and cardiovascular death) was recorded. . We conducted a miRNA expression analysis in plasma from 19 patients with and without cardiovascular events. The miRNAs selected (miR-22-3p, miR-107, and miR-146a-5p) were later measured in 166 patients (47% male, median age 77 (IQR 70-81) years) and all were associated with a higher risk of MACE. The addition of miR-107 and miR-146a-5p to the 2MACE score significantly increased the predictive performance (c-indexes: 0.759 vs. 0.694, = 0.004), and the model with three miRNAs also improved the predictive performance compared to the original score (c-indexes: 0.762 vs. 0.694, = 0.012). 2MACE models with the addition of miRNAs presented higher net benefit and potential clinical usefulness. . Higher miR-22-3p andmiR-107 and lower miR-146a-5p levels were associated with a higher risk of MACE. The addition of these miRNAs to the 2MACE score significantly increased the predictive performance for MACE, which may aid to some extent in the decision-making process about risk stratification in AF.
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http://dx.doi.org/10.3390/jcm9113645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698124PMC
November 2020

Particulate Matter and Temperature: Increased Risk of Adverse Clinical Outcomes in Patients With Atrial Fibrillation.

Mayo Clin Proc 2020 11;95(11):2360-2369

Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.

Objective: To test the hypothesis that particulate matter with an aerodynamic diameter of less than 10 μm (PM) and temperature are associated with an increased risk of adverse clinical outcomes in patients with atrial fibrillation (AF) taking vitamin K antagonists (VKAs).

Patients And Methods: We included patients with AF whose condition was stable while taking VKAs (international normalized ratio, 2.0 to 3.0) for 6 months seen in a tertiary hospital (recruitment from May 1, 2007, to December 1, 2007). During a median follow-up of 6.5 years (interquartile range, 4.3 to 7.9 years), ischemic strokes, major bleeding, adverse cardiovascular events, and mortality were recorded. From 2007 to 2016, data on average temperature and PM were compared with clinical outcomes.

Results: The study group included 1361 patients (663 [48.7%] male; median age, 76 years [interquartile range, 71 to 81 years]). High PM and low temperatures were associated with higher risk of major bleeding (adjusted hazard ratio [aHR], 1.44; 95% CI, 1.22 to 1.70 and aHR, 1.03; 95% CI, 1.01 to 1.05, respectively) and mortality (aHR, 1.50; 95% CI, 1.34 to 1.69 and aHR, 1.04; 95% CI, 1.02 to 1.06, respectively); PM was also associated with ischemic stroke and temperature with cardiovascular events. The relative risk (RR) for cardiovascular events and mortality increased in months in the lower quartile of temperature (RR, 1.12; 95% CI, 1.04 to 1.21 and RR, 1.41; 95% CI, 1.15 to 1.74, respectively). Comparing seasons, there were higher risks of cardiovascular events in spring, autumn, and winter than in summer, whereas the risk of mortality increased only in winter.

Conclusion: In patients with AF taking VKAs, high PM and low temperature were associated with increased risk of ischemic stroke and cardiovascular events, respectively. Both factors increased major bleeding and mortality risks, which were higher during colder months and seasons.
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http://dx.doi.org/10.1016/j.mayocp.2020.05.046DOI Listing
November 2020

Factor XII in PMM2-CDG patients: role of N-glycosylation in the secretion and function of the first element of the contact pathway.

Orphanet J Rare Dis 2020 10 9;15(1):280. Epub 2020 Oct 9.

Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, CIBERER, Ronda de Garay S/N, 30003, Murcia, Spain.

Background: Congenital disorders of glycosylation (CDG) are rare diseases with impaired glycosylation and multiorgan disfunction, including hemostatic and inflammatory disorders. Factor XII (FXII), the first element of the contact phase, has an emerging role in hemostasia and inflammation. FXII deficiency protects against thrombosis and the p.Thr309Lys variant is involved in hereditary angioedema through the hyperreactivity caused by the associated defective O-glycosylation. We studied FXII in CDG aiming to supply further information of the glycosylation of this molecule, and its functional and clinical effects. Plasma FXII from 46 PMM2-CDG patients was evaluated by coagulometric and by Western Blot in basal conditions, treated with N-glycosydase F or activated by silica or dextran sulfate. A recombinant FXII expression model was used to validate the secretion and glycosylation of wild-type and variants targeting the two described FXII N-glycosylation sites (p.Asn230Lys; p.Asn414Lys) as well as the p.Thr309Lys variant.

Results: PMM2-CDG patients had normal FXII levels (117%) but high proportions of a form lacking N-glycosylation at Asn414. Recombinant FXII p.Asn230Lys, and p.Asn230Lys&p.Asn414Lys had impaired secretion and increased intracellular retention compared to wild-type, p.Thr309Lys and p.Asn414Lys variants. The hypoglycosylated form of PMM2-CDG activated similarly than FXII fully glycosylated. Accordingly, no PMM2-CDG had angioedema. FXII levels did not associate to vascular events, but hypoglycosylated FXII, like hypoglycosylated transferrin, antithrombin and FXI levels did it.

Conclusions: N-glycosylation at Asn230 is essential for FXII secretion. PMM2-CDG have high levels of FXII lacking N-glycosylation at Asn414, but this glycoform displays similar activation than fully glycosylated, explaining the absence of angioedema in CDG.
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http://dx.doi.org/10.1186/s13023-020-01564-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547467PMC
October 2020

Influence of the matrix type over the concentration of GDF-15.

J Investig Med 2020 12 8;68(8):1402-1404. Epub 2020 Sep 8.

Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria (IMIBArrixaca), CIBERCV, Murcia, Spain

Growth differentiation factor 15 (GDF-15) has been suggested as a prognostic biomarker for bleeding and mortality in atrial fibrillation (AF). To date, serum and EDTA matrices are standardized for the GDF-15 assay but it is unclear if it can be measured also in citrate. In this study, we aim to investigate if the Elecsys GDF-15 assay (Roche Diagnostics, Mannheim, Germany) can be determined accurately in citrate samples in a cohort of 10 patients with AF and 10 healthy controls. From January 2018 to March 2018, we included healthy controls and patients with AF under vitamin K antagonists in a tertiary hospital. Blood samples were drawn in both groups. We included 10 controls (50% males, mean age 36.4±8.9 years) and 10 patients with AF (80% males, mean age 76.5±16.6 years). The mean GDF-15 levels were increased in patients with AF in comparison to healthy controls, as expected by the presence of a heart-related condition and the higher age of this population. In healthy controls, GDF-15 levels showed an optimal correlation between EDTA-serum (r=0.975; p<0.001), EDTA-citrate (r=0.972; p<0.001), and serum-citrate (r=0.997; p<0.001) samples. This was also observed in patients with AF: EDTA-serum (r=0.975; p<0.001), serum-citrate (r=0.835; p=0.003), and EDTA-citrate (r=0.768; p=0.009). Our results demonstrate that citrate samples may be used for the determination of GDF-15 in AF given the positive and good correlation with EDTA and serum matrices. Further studies should validate these observations.
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http://dx.doi.org/10.1136/jim-2020-001351DOI Listing
December 2020

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

Int J Clin Pract 2020 Dec 25;74(12):e13634. Epub 2020 Aug 25.

Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), University of Murcia, CIBERCV, Spain.

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.
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http://dx.doi.org/10.1111/ijcp.13634DOI Listing
December 2020

Recommendations on antithrombotic treatment during the COVID-19 pandemic. Position statement of the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology.

Rev Esp Cardiol (Engl Ed) 2020 Sep 19;73(9):749-757. Epub 2020 Jun 19.

Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, CIBERCV, El Palmar, Murcia, Spain. Electronic address:

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.
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http://dx.doi.org/10.1016/j.rec.2020.04.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303617PMC
September 2020

Treatment strategies for patients with atrial fibrillation and anticoagulant-associated intracranial hemorrhage: an overview of the pharmacotherapy.

Expert Opin Pharmacother 2020 Oct 13;21(15):1867-1881. Epub 2020 Jul 13.

Department of Cardiology, Hospital Clínico Universitario Virgen De La Arrixaca, Instituto Murciano De Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, Murcia , Spain.

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.
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http://dx.doi.org/10.1080/14656566.2020.1789099DOI Listing
October 2020

ALG12-CDG: An unusual patient without intellectual disability and facial dysmorphism, and with a novel variant.

Mol Genet Genomic Med 2020 08 12;8(8):e1304. Epub 2020 Jun 12.

Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.

Background: Congenital disorder of glycosylation (CDG) type I is a group of rare disorders caused by recessive mutations in up to 25 genes that impair the N-glycan precursor formation and its transfer to proteins resulting in hypoglycosylation of multiple proteins. Congenital disorder of glycosylation causes multisystem defects usually with psychomotor delay that is diagnosed in the infancy. We aim to supply further evidences supporting that CDG may be underestimated.

Methods: Antithrombin and factor XI were studied by chromogenic and coagulometric methods. Hypoglycosylation of plasma proteins was evaluated by western blot, HPLC, Q-TOF, and RP-LC-MRM-MS. Genetic analysis included whole exome, Sanger sequencing, and PCR-allele specific assay.

Results: We here present an intriguing patient with an exceptional phenotype: 25-year-old women with a ventricular septal defect and severe idiopathic scoliosis but no facial dysmorphism, who dances as a professional, and has a University degree. Congenital disorder of glycosylation diagnosis started through the identification of antithrombin deficiency without SERPINC1 defect and the detection of hypoglycosylated forms. Increased levels of hypoglycosylated forms of F XI (also with significant deficiency) and transferrin were also detected. Whole exome analysis showed a novel homozygous ALG12 variant c.77T>A, p.(Val26Asp) supporting an ALG12-CDG diagnosis. It also showed three new variants in KMT2D, and a mild, known ALG6 variant.

Conclusions: This novel ALG12-CDG patient (the 13th reported) underlines the heterogeneity of this CDG and broadens its phenotypical spectrum, supports that these disorders are underestimated, and suggests that combination of global hypoglycosylation with specific gene defects might determine the clinical manifestations of CDG patients.
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http://dx.doi.org/10.1002/mgg3.1304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434597PMC
August 2020

Predicting Adverse Events beyond Stroke and Bleeding with the ABC-Stroke and ABC-Bleeding Scores in Patients with Atrial Fibrillation: The Murcia AF Project.

Thromb Haemost 2020 Aug 7;120(8):1200-1207. Epub 2020 Jun 7.

Department of Hematology and Clinical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, Murcia, Spain.

Background:  The ABC (age, biomarkers, and clinical history)-stroke and ABC-bleeding are biomarker-based scores proposed to predict stroke and bleeding, but non-specificity of biomarkers is common, predicting different clinical events at the same time. We assessed the predictive performance of the ABC-stroke and ABC-bleeding scores, for outcomes beyond ischemic stroke and major bleeding, in a cohort of atrial fibrillation (AF) patients.

Methods:  We included AF patients stable on vitamin K antagonists for 6 months. The ABC-stroke and ABC-bleeding were calculated and the predictive values for myocardial infarction (MI), acute heart failure (HF), a composite of cardiovascular events, and all-cause deaths were compared.

Results:  We included 1,044 patients (49.2% male; median age 76 [71-81] years). During 6.5 (4.3-7.9) years, there were 58 (5.6%) MIs, 98 (9.4%) acute HFs, 167 (16%) cardiovascular events, and 418 (40%) all-cause deaths. There were no differences in mean ABC-stroke and ABC-bleeding scores in patients with/without MI ( = 0.367 and  = 0.286, respectively); both scores were higher in patients with acute HF, cardiovascular events, or death (all  < 0.05). Predictive performances for the ABC-stroke and ABC-bleeding scores were similar, ranging from "poor" for MI (-indexes ∼0.54), "moderate" for acute HF and cardiovascular events (-indexes ∼0.60 and ∼0.64, respectively), and "good" for all-cause mortality (-indexes > 0.70). Clinical usefulness whether assessed by ABC-stroke or ABC-bleeding was similar for various primary endpoints.

Conclusion:  In AF patients, the ABC-stroke and ABC-bleeding scores demonstrated similar predictive ability for outcomes beyond stroke and bleeding, including MI, acute HF, a composite of cardiovascular events, and all-cause deaths. This is consistent with nonspecificity of biomarkers that predict "sick" patients or poor prognosis overall.
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http://dx.doi.org/10.1055/s-0040-1712914DOI Listing
August 2020

[Recommendations on antithrombotic treatment during the COVID-19 pandemic. Position statement of the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology].

Rev Esp Cardiol 2020 Sep 22;73(9):749-757. Epub 2020 Apr 22.

Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, CIBERCV, El Palmar, Murcia, España.

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.
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http://dx.doi.org/10.1016/j.recesp.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176384PMC
September 2020

Influence of sex on long-term prognosis in patients with atrial fibrillation treated with oral anticoagulants. Results from the prospective, nationwide FANTASIIA study.

Eur J Intern Med 2020 08 14;78:63-68. Epub 2020 Apr 14.

Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.

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<0.001). Women had higher rate of cardiovascular risk factors and higher mean of CHADS-VASc (4.4 ± 1.4 vs 3.7 ± 1.6, p<0.001) and HAS-BLED (2.1 ± 1.0 vs 1.9 ± 1.1, p<0.001) than men. After 3 years of follow-up, rates of major events were similar in both groups with limit difference for all-cause mortality (4.4%/year in women vs 5.6%/year in men; p = 0.056). However, all the composite events were more frequent in women. We observed in the non-adjusted adverse events lower rate of all-cause mortality (HR 0.62, 95%CI 0.47-0.81; p<0.001), composite 1 outcomes (HR 0.80, 95%CI 0.65-0.98; p = 0.029) and composite 2 (HR 0.77, 95%CI 0.64-0.94; p = 0.010) in women compared with men. In multivariate Cox regression analysis observed that female sex was an independently protector factor for all-cause mortality and for the composite outcomes 1 and 2.

Conclusions: In this "real world" study of anticoagulated AF patients, women could have a protective role against development of adverse events, mainly on all-cause mortality and combined events.
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http://dx.doi.org/10.1016/j.ejim.2020.04.012DOI Listing
August 2020

Murcia atrial fibrillation project II: protocol for a prospective observational study in patients with atrial fibrillation.

BMJ Open 2019 12 15;9(12):e033712. Epub 2019 Dec 15.

Department of Hematology and Clinical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain

Introduction: Atrial 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 Analysis: Prospective 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 Dissemination: All 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.
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http://dx.doi.org/10.1136/bmjopen-2019-033712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924708PMC
December 2019

The Use of Biomarkers in Clinical Management Guidelines: A Critical Appraisal.

Thromb Haemost 2019 Dec 9;119(12):1901-1919. Epub 2019 Sep 9.

Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, University of Murcia, Murcia, Spain.

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.
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http://dx.doi.org/10.1055/s-0039-1696955DOI Listing
December 2019

Identification of 58 Mutations (26 Novel) in 94 of 109 Symptomatic Spanish Probands with Protein C Deficiency.

Thromb Haemost 2019 Sep 29;119(9):1409-1418. Epub 2019 Jun 29.

Grupo de Investigación en Hemostasia, Trombosis, Arteriosclerosis y Biología Vascular, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Hospital Universitario y Politécnico La Fe, Valencia, Spain.

Presently, no data on the molecular basis of hereditary protein C (PC) deficiency in Spain is available. We analyzed the PC gene () in 109 patients with symptomatic PC deficiency and in 342 relatives by sequencing the 9 exons and their flanking intron regions. In 93 probands, we found 58 different mutations (26 novel). Thirty-seven consisted of a nucleotide change, mainly missense mutations, 1 was a 6-nucleotide insertion causing the duplication of 2 amino acids, and 4 were deletions of 1, 3, 4, and 16 nucleotides. Nine mutations caused type II deficiencies, with the presence of normal antigen levels but reduced anticoagulant activity. Using a PC level of 70% as lowest normal limit, we found no mutations in 16 probands and 25 relatives with PC levels ≤ 70%. On the contrary, 4 probands and 12 relatives with PC levels > 70% carried the mutation identified in the proband. The spectrum of recurrent mutations in Spain is different from that found in the Netherlands, where the most frequent mutations were p.Gln174* and p.Arg272Cys, and is more similar to that found in France, where the most frequent were p.Arg220Gln and p.Pro210Leu. In our study, p.Val339Met (9 families), p.Tyr166Cys (7), p.Arg220Gln (6), and p.Glu58Lys (5) were the most prevalent. This study confirms the considerable heterogeneity of the genetic abnormality in PC deficiencies, and allowed genetic counseling to those individuals whose PC levels were close to the lower limit of the normal reference range.
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http://dx.doi.org/10.1055/s-0039-1692440DOI Listing
September 2019

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

Stroke 2019 06 14;50(6):1372-1379. Epub 2019 May 14.

Department of Hematology and Clinical Oncology, Hospital General Universitario Morales Meseguer, Instituto Murciano de Investigación Biosanitaria, University of Murcia, Spain (J.G., V.V., V.R.).

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 CHADS-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 (β-trace protein) concentrations were quantified. During follow-up, all adverse events were recorded, and biomarkers were added to CHADS-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 CHADS-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 CHADS-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.
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http://dx.doi.org/10.1161/STROKEAHA.118.024305DOI Listing
June 2019

Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals.

Clin Pharmacol Ther 2019 06 17;105(6):1477-1491. Epub 2019 Feb 17.

Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene-gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7-10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived.
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http://dx.doi.org/10.1002/cpt.1323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542461PMC
June 2019

Increasing therapy-related myeloid neoplasms in multiple myeloma.

Eur J Clin Invest 2019 Feb 7;49(2):e13050. Epub 2018 Dec 7.

Servicio de Hematología y Oncología Médica, Hospital General Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.

Background: Despite the longer survival achieved in multiple myeloma (MM) patients due to new therapy strategies, a concern is emerging regarding an increased risk of secondary primary malignancies (SPMs) and how to characterize those patients at risk. We performed a retrospective study covering a 28-year follow-up period (1991-2018) in a tertiary single institution.

Material And Methods: Data of 403 MM patients were recorded and compared with the epidemiologic register of the population area covered by our centre, calculating the standardize incidence ratio (SIR) for the different types of SPMs diagnosed in the MM cohort. Fine and Gray regression models were used to identify risk factors for SPMs.

Results: Out of the 403 MM patients, 23 (5.7%) developed SPMs: 13 therapy-related myeloid (TRM) malignancies (10 of them (77%) myelodysplastic syndrome (MDS), 1 acute lymphoid leukaemia and 9 solid neoplasms. In the MM cohort, the relative risk of MDS was significantly higher than in the general population. Survival of patients with TRM malignancies was poor with a median of 4 months from the diagnosis, and most of them showed complex karyotype. Within the MM subset, multivariable analysis showed a higher risk of TRM malignancies in patients that previously received prolonged treatment with lenalidomide (>18 months).

Conclusions: Though the improvement in MM outcome during the last decades is an unprecedented achievement, it has been accompanied by the rise in TRM malignancies with complex cytogenetic profile and poor prognosis that are in the need of an improved biologic and therapeutic approach.
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http://dx.doi.org/10.1111/eci.13050DOI Listing
February 2019

Estimated Effectiveness and Safety of Nonvitamin K Antagonist Oral Anticoagulants Compared With Optimally Acenocoumarol Anticoagulated "Real-World" in Patients With Atrial Fibrillation.

Am J Cardiol 2018 09 2;122(5):785-792. Epub 2018 Jun 2.

Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

Nonvitamin K antagonist oral anticoagulants (NOACs) have been proposed as an alternative to vitamin K antagonists in atrial fibrillation (AF) patients but the comparative benefits between NOACs and optimally anticoagulated patients is unknown. We estimated the absolute benefit in clinical outcomes rates of real-world effect of NOACs in optimally anticoagulated AF patients with acenocoumarol. We included 1,361 patients stable on acenocoumarol with time in therapeutic range of 100% and 6.5 years of follow-up. Estimation of clinical events avoided was calculated applying hazard ratio, absolute and relative risk reduction from the real-world meta-analysis. Compared with an optimally anticoagulated population, dabigatran 110 mg had the highest estimated stroke reduction (0.97%/year vs 1.47%/year; p = 0.002), and the benefit was higher than in RE-LY trial. For major bleeding, apixaban showed the highest estimated reduction (1.81%/year vs 2.83%/year; p <0.001). For mortality, the largest estimated reduction was with apixaban (2.68%/year). For gastrointestinal bleeding, only apixaban had a significant reduction compared with acenocoumarol (0.69%/year vs 1.10%/year; p = 0.004), and the reduction was significantly higher than in ARISTOTLE trial. All NOACs showed significantly lower rates for intracranial hemorrhage and had a positive Net Clinical Benefit compared with acenocoumarol. Apixaban showed the highest extended estimated Net Clinical Benefit 2.64 (95%CI 2.34 to 2.96). In conclusion, in optimally acenocoumarol anticoagulated AF patients, estimated reductions in all clinical outcomes with various NOACs are evident, with the best effectiveness and safety profile with apixaban. Indeed, the estimated effect with "real world" NOACs would probably be higher than that seen in phase-III clinical trials.
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http://dx.doi.org/10.1016/j.amjcard.2018.05.012DOI Listing
September 2018

miR-146a deficiency in hematopoietic cells is not involved in the development of atherosclerosis.

PLoS One 2018 14;13(6):e0198932. Epub 2018 Jun 14.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.

Background: Atherosclerosis involves activation of the IRAK1/TRAF6/NF-κB inflammatory cascade, which is negatively regulated by miR146a. Previous studies showed that the TT genotype of rs2431697, located near the miR-146a gene, drives lower miR-146a transcription and predicts adverse cardiovascular events in anticoagulated atrial fibrillation patients. Moreover, systemic miR-146a administration protects mice from atherosclerosis. Here we evaluated the ability of miR-146a expression in the hematopoietic component to regulate atherosclerosis in low-density lipoprotein receptor-null mice (Ldlr-/-).

Methods And Results: Lethally-irradiated Ldlr-/- mice transplanted with bone marrow from wild-type or miR-146a-null mice were fed an atherogenic diet for 8 and 20 weeks. Irak1, Traf6 and MIR146A expression were quantified in thoracic aorta by qRT-PCR and Western blot. Aortic plaque size and composition were characterized by Oil-Red staining and immunohistochemistry and leukocyte recruitment by intravital microscopy. Blood cell counts were similar in fat-fed Ldlr-/-mice with or without hematopoietic miR-146a expression. However, plasma cholesterol decreased in fat-fed Ldlr-/-mice transplanted with bone marrow deficient for miR-146a. Finally, aortic atherosclerosis burden and recruitment of leukocytes into the vessel wall were undistinguishable between the two groups, despite higher levels of Irak1 and Traf6 mRNA and protein in the aorta of fat-fed mice lacking hematopoietic miR-146a expression.

Conclusions: miR-146a deficiency exclusively in hematopoietic cells modulates cholesterol levels in plasma and the expression of its targets in the artery wall of fat-fed Ldlr-/- mice, but does not accelerate atherosclerosis. Atheroprotection upon systemic miR-146a administration may therefore be caused by specific effects on vascular cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198932PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002112PMC
December 2018

Perioperative and Periprocedural Management of Antithrombotic Therapy: Consensus Document of SEC, SEDAR, SEACV, SECTCV, AEC, SECPRE, SEPD, SEGO, SEHH, SETH, SEMERGEN, SEMFYC, SEMG, SEMICYUC, SEMI, SEMES, SEPAR, SENEC, SEO, SEPA, SERVEI, SECOT and AEU.

Rev Esp Cardiol (Engl Ed) 2018 Jul 8;71(7):553-564. Epub 2018 Jun 8.

Servicio de Medicina Intensiva, Hospital Clínico Universitario, Valencia, Spain.

During the last few years, the number of patients receiving anticoagulant and antiplatelet therapy has increased worldwide. Since this is a chronic treatment, patients receiving it can be expected to need some kind of surgery or intervention during their lifetime that may require treatment discontinuation. The decision to withdraw antithrombotic therapy depends on the patient's thrombotic risk versus hemorrhagic risk. Assessment of both factors will show the precise management of anticoagulant and antiplatelet therapy in these scenarios. The aim of this consensus document, coordinated by the Cardiovascular Thrombosis Working Group of the Spanish Society of Cardiology, and endorsed by most of the Spanish scientific societies of clinical specialities that may play a role in the patient-health care process during the perioperative or periprocedural period, is to recommend some simple and practical guidelines with a view to homogenizing daily clinical practice.
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http://dx.doi.org/10.1016/j.rec.2018.01.029DOI Listing
July 2018

Oral anticoagulation and comorbidities; too many details for clinical practice?

Int J Cardiol 2018 08;264:93-94

Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, IMIB-Arrixaca, Universidad de Murcia, Spain.

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http://dx.doi.org/10.1016/j.ijcard.2018.03.115DOI Listing
August 2018

A Propensity Score Matched Comparison of Clinical Outcomes in Atrial Fibrillation Patients Taking Vitamin K Antagonists: Comparing the "Real-World" vs Clinical Trials.

Mayo Clin Proc 2018 08 2;93(8):1065-1073. Epub 2018 May 2.

Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address:

Objective: To investigate the incidence and risk of adverse clinical outcomes in a "real-world" cohort of patients with atrial fibrillation (AF) anticoagulated with vitamin K antagonists (VKAs) from the Murcia AF Project in comparison with the warfarin arm of the randomized clinical trial (RCT) AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation).

Patients And Methods: We included 1361 patients with AF from the Murcia AF Project (recruitment from May 1, 2007, to December 1, 2007) and 2293 from the AMADEUS trial (started in September 2003 and primary completed in March 2006), all taking VKA treatment. After propensity score matching (PSM), we investigated differences in rates and risks of several events, including major bleeding, ischemic stroke, and all-cause mortality at 365 (interquartile range, 275-428) days of follow-up.

Results: After PSM there were 1324 patients for the comparative analysis, whereby annual event rates for most adverse events were significantly higher in the "real-world" population. Cox regression analyses demonstrated that the risk of primary outcomes was also increased in the "real-world" (vs RCT: hazard ratio [HR], 6.32; 95% CI, 2.84-14.03 for major bleeding; HR, 3.56, 95% CI, 1.22-10.42 for ischemic stroke; HR, 5.13, 95% CI, 3.02-8.69 for all-cause mortality). The risk of all other adverse events was higher in the real-world cohort, except for cardiovascular mortality.

Conclusion: This study comparing the Murcia AF Project and the AMADEUS trial demonstrates that there is a great heterogeneity in both populations, which is translated into a higher risk of several adverse outcomes in the real-world cohort, including major bleeding, ischemic stroke, and mortality.
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http://dx.doi.org/10.1016/j.mayocp.2018.01.028DOI Listing
August 2018

Optimizing Vitamin K Antagonist Treatment in Patients with Mechanical Heart Valve Prosthesis.

Thromb Haemost 2018 05 6;118(5):806-807. Epub 2018 Apr 6.

Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, CIBER-CV, Universidad de Murcia, Murcia, Spain.

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http://dx.doi.org/10.1055/s-0038-1641737DOI Listing
May 2018
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