Publications by authors named "Eduard Shantsila"

149 Publications

Hypertension and sleep health: a multidimensional puzzle.

J Hypertens 2021 Apr;39(4):600-601

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002743DOI Listing
April 2021

Effects of antithrombotic drugs on the prothrombotic state in patients with atrial fibrillation: The west Birmingham atrial fibrillation project.

Thromb Res 2021 Apr 9;200:149-155. Epub 2021 Feb 9.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Health Services Research, University of Liverpool, United Kingdom. Electronic address:

Background: Direct oral anticoagulants (DOACs) are known to prevent thrombosis but there is limited information about their activity on the clot formation and lysis cascade.

Objectives: This study assesses the role of apixaban, one of the four licenced DOACs, on clot dynamics in patients with atrial fibrillation (AF).

Methods: We compared haemostatic and clot lysis characteristics between a group of patients with AF (n = 47) and a "disease control" group with ischaemic heart disease but in sinus rhythm (n = 39). Subsequently, we conducted clot structure studies in 3 groups of patients with AF on different antithrombotic drugs: warfarin (n = 60), apixaban (n = 60) or antiplatelets (n = 62) and in patients with AF naïve to oral anticoagulants before and after 3-months treatment with apixaban (n = 32). Haemostasis was investigated by a viscoelastic, whole blood technique (Thromboelastography/TEG), a "microplate-reader based", citrated plasma technique (microplate assay), immunoassays to determine plasma concentrations of plasminogen activator inhibitor-1 (PAI-1), tissue-Plasminogen Activator (t-PA), D-dimer and finally platelet derived and apoptotic microparticles.

Results: Patients with AF have more potent thrombogenesis based on microplate assay indices [Rate of clot formation (p = 0.03, ƞ = 0.06), Maximum optical density (p < 0.001, ƞ = 0.05)] and delayed fibrinolysis [Rate of clot dissolution (p = 0.005, ƞ = 0.17)] with increased levels of apoptotic microparticles (p = 0.02, ƞ = 0.06) compared with the 'disease control' group. Apixaban was more effective in attenuating prothrombotic characteristics assessed by TEG {R (ε = 0.21), K (ε = 0.16) and angle [mean difference (MD), 95% Confidence Intervals (CI), vs warfarin 5, 0.96-8.6 and 8, 3.8-11.4 vs antiplatelets], (p < 0.001 for all indices)} compared with the other treatment groups. Patients on apixaban had lower D-dimer (p < 0.001, ε = 0.17) and tPA (p = 0.03, MD 90, 95%CI 6-150 vs warfarin and MD 90, 95% CI 4-150 vs antiplatelets) levels. From the microplate assay analysis, warfarin and apixaban demonstrated comparable activity based on multiple indices, both superior to antiplatelets. However, warfarin was associated with reduced fibrin network robustness (Max. optical density p < 0.001, ε = 0.1). Apixaban inhibited thrombosis, amplified fibrinolysis and decreased D-dimer (p = 0.001, r = 0.4) levels in the follow up study.

Conclusions: Patients with AF have impaired haemostasis and elevated levels of apoptotic microparticles. Apixaban appears to affect plasma prothrombotic characteristics in a distinctive manner compared with warfarin and to reduce biomarkers associated with adverse cardiovascular events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2021.02.005DOI Listing
April 2021

Observations on clot properties in atrial fibrillation: Relation to renal function and choice of anticoagulant.

Thromb Res 2021 Jan 7;197:69-76. Epub 2020 Nov 7.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; and Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address:

Introduction: Atrial fibrillation (AF) is associated with increased risk of stroke and thromboembolism. Patients with AF have a higher incidence of renal impairment, which may influence the risks of systemic thromboembolism or bleeding. We determined how different oral anticoagulants affect plasma clot properties and whether progressive renal dysfunction affects plasma clot properties in patients on warfarin.

Materials And Methods: We studied 257 patients with AF receiving oral anticoagulants. Furthermore, we recruited 192 separate patients with AF on warfarin and divided them in 4 groups based on estimated glomerular filtration rate (eGFR). Platelet poor plasma was prepared and clot formation and fibrinolysis was monitored kinetically up to 1 h.

Results: Rate of clot formation was significantly slower with dabigatran and rivaroxaban. Time between 50% clotting and 50% lysis was prolonged in patients receiving warfarin compared to NOACs. Time to 50% lysis from maximum absorbance was significantly shorter in patients receiving rivaroxaban. Time between 50% clotting and 50% lysis became significantly prolonged with worsening eGFR. Time to 50% lysis from maximum absorbance was prolonged as renal function worsened.

Conclusions: Compared to warfarin, NOACs differently modulate coagulation and fibrinolysis under ex vivo conditions. Worsening renal function in AF patients on warfarin prolongs fibrinolysis, potentially increasing the risk of thrombosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2020.10.039DOI Listing
January 2021

Spironolactone in Atrial Fibrillation With Preserved Cardiac Fraction: The IMPRESS-AF Trial.

J Am Heart Assoc 2020 09 10;9(18):e016239. Epub 2020 Sep 10.

Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart & Chest Hospital Liverpool United Kingdom.

Background Patients with permanent atrial fibrillation have poor outcomes, exercise capacity, and quality of life even on optimal anticoagulation. Based on mechanistic and observational data, we tested whether the mineralocorticoid receptor antagonist spironolactone can improve exercise capacity, E/e' ratio, and quality of life in patients with permanent atrial fibrillation and preserved ejection fraction. Methods and Results The double-masked, placebo-controlled IMPRESS-AF (Improved Exercise Tolerance in Heart Failure With Preserved Ejection Fraction by Spironolactone on Myocardial Fibrosis in Atrial Fibrillation) trial (NCT02673463) randomized 250 stable patients with permanent atrial fibrillation and preserved left ventricular ejection fraction to spironolactone 25 mg daily or placebo. Patients were followed for 2 years. The primary efficacy outcome was peak oxygen consumption on cardiopulmonary exercise testing at 2 years. Secondary end points included 6-minute walk distance, E/e' ratio, quality of life, and hospital admissions. Spironolactone therapy did not improve peak oxygen consumption at 2 years (14.0 mL/min per kg [SD, 5.4]) compared with placebo (14.5 [5.1], adjusted treatment effect, -0.28; 95% CI, -1.27 to 0.71]; =0.58). The findings were consistent across all sensitivity analyses. There were no differences in the 6-minute walking distance (adjusted treatment effect, -8.47 m; -31.9 to 14.9; =0.48), E/e' ratio (adjusted treatment effect, -0.68; -1.52 to 0.17, =0.12), or quality of life (=0.74 for EuroQol-5 Dimensions, 5-level version quality of life questionnaire and =0.84 for Minnesota Living with Heart Failure). At least 1 hospitalization occurred in 15% of patients in the spironolactone group and 23% in the placebo group (=0.15). Estimated glomerular filtration rate was reduced by 6 mL/min in the spironolactone group with <1-unit reduction in controls (<0.001). Systolic blood pressure was reduced by 7.2 mm Hg (95% CI, 2.2-12.3) in the spironolactone group versus placebo (=0.005). Conclusions Spironolactone therapy does not improve exercise capacity, E/e' ratio, or quality of life in patients with chronic atrial fibrillation and preserved ejection fraction. Registration UTL: https://www.clini​caltr​ial.gov; Unique identifier: NCT02673463. EudraCT number 2014-003702-33.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.016239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726985PMC
September 2020

Blood pressure targets in atrial fibrillation.

Eur Heart J 2020 08;41(30):2860-2862

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehaa319DOI Listing
August 2020

Imaging, biomarker and invasive assessment of diffuse left ventricular myocardial fibrosis in atrial fibrillation.

J Cardiovasc Magn Reson 2020 02 10;22(1):13. Epub 2020 Feb 10.

Department of Cardiology, Leeds General Infirmary, X39 Cardiology Offices, Great George St, Leeds, LS1 3EX, UK.

Background: Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation.

Methods: LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis.

Results: On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression.

Conclusion: LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12968-020-0603-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008543PMC
February 2020

Guideline-Adherent Treatment for Stroke and Death in Atrial Fibrillation Patients From UK and Japanese AF Registries.

Circ J 2019 11 6;83(12):2434-2442. Epub 2019 Nov 6.

Institute of Cardiovascular Sciences, University of Birmingham.

Background: Guideline-adherent antithrombotic treatment (ATT) reduces the risk of stroke and death in patients with atrial fibrillation (AF). However, the effect of ATT adherence among different ethnicities remains uncertain. We compared the prognosis of AF patients in Japan and the UK according to guideline adherence status.Methods and Results:We compared the clinical characteristics and outcomes of AF patients from the Fushimi AF registry (Japan; n=4,239) and the Darlington AF registry (UK; n=2,259). ATT adherence was assessed against the Japanese Circulation Society Guidelines and UK National Institute for Health and Care Excellence guidelines. The rates of guideline-adherent ATT were 58.6% and 50.8% in the Fushimi and Darlington registries, respectively. There was no significant difference in 1-year stroke rates between Fushimi and Darlington (2.6% vs. 3.0%, P=0.342). On multivariate logistic regression analysis, non-guideline adherent-ATT was significantly associated with an increased risk of stroke (odds ratio [OR]: 1.69, 95% confidence interval [CI]: 1.21-2.34, P=0.002 for undertreatment, OR: 2.13, 95% CI: 1.19-3.80, P=0.010 for overtreatment). No significant interaction for ATT and the 2 populations was found in the incidence of stroke, all-cause death, and the composite outcome.

Conclusions: Approximately half of the AF patients received optimal ATT according to guideline recommendations, which was associated with a lower risk of stroke. Furthermore, there was no interaction for the 2 populations and the influence of ATT adherence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-19-0546DOI Listing
November 2019

Microparticles and cardiovascular diseases.

Ann Med 2019 May - Jun;51(3-4):193-223. Epub 2019 Jun 17.

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

Microparticles are a distinctive group of small vesicles, without nucleus, which are involved as significant modulators in several physiological and pathophysiological mechanisms. Plasma microparticles from various cellular lines have been subject of research. Data suggest that they are key players in development and manifestation of cardiovascular diseases and their presence, in high levels, is associated with chronic inflammation, endothelial damage and thrombosis. The strong correlation of microparticle levels with several outcomes in cardiovascular diseases has led to their utilization as biomarkers. Despite the limited clinical application at present, their significance emerges, mainly because their detection and enumeration methods are improving. This review article summarizes the evidence derived from research, related with the genesis and the function of microparticles in the presence of various cardiovascular risk factors and conditions. The current data provide a substrate for several theories of how microparticles influence various cellular mechanisms by transferring biological information.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07853890.2019.1609076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877885PMC
June 2020

Heart Failure and Stroke.

Curr Heart Fail Rep 2018 10;15(5):287-296

Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.

Purpose: Ischemic stroke significantly contributes to morbidity and mortality in heart failure (HF). The risk of stroke increases significantly, with coexisting atrial fibrillation (AF). An aggravating factor could be asymptomatic paroxysms of AF (so-called silent AF), and therefore, the risk stratification in these patients remains difficult. This review provides an overview of stroke risk in HF, its risk stratification, and stroke prevention in these patients.

Recent Findings: Stroke risk stratification in HF patients remains an important issue. Recently, the CHADS-VASc score, originally developed to predict stroke risk in AF patients, had been reported to be a predictive for strokes in HF patients regardless of AF being present. Furthermore, there are several independent risk factors (e.g., hypertension, diabetes mellitus, prior stroke) described. Based on the current evidence, HF should be considered as an independent risk factor for stroke. The CHADS-VASc score might be useful to predict stroke risk in HF patients with or without AF in clinical routine. However, there is only a recommendation for the oral anticoagulation use in patients with concomitant HF and AF, while in patients with HF and no AF, individualized risk stratification is preferred. Current guidelines recommend to prefer non-vitamin Kantagonist anticoagulants over warfarin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11897-018-0405-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132785PMC
October 2018

Prognostic implication of monocytes in atrial fibrillation: The West Birmingham Atrial Fibrillation Project.

PLoS One 2018 18;13(7):e0200373. Epub 2018 Jul 18.

Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom.

Background And Objectives: High monocyte counts are related to adverse outcomes in cardiovascular disease. Their role in prognostication in patients with atrial fibrillation (AF) is unknown. We investigated whether monocyte counts are useful as a marker of prognosis in patients with AF.

Methods: Monocyte counts were obtained from blood samples in 881 AF patients. Study outcomes were (i) all-cause death; (ii) major adverse cardiovascular events; (iii) stroke, TIA or other systemic embolism (SSE); and (iv) major bleeding.

Results: Median follow up was 7.2 years; 44% of patients died, 48% developed MACE; 9% had SSE and 5% had major bleeding. On Cox regression, after adjustment for CHA2DS2-VASc score, the highest quartile of monocyte counts (i.e., ≥580 μL vs. other quartiles) was associated with increased risk of death (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.31-2.05, p<0.001) and MACE (HR 1.58, 95% CI 1.28-1.96, p<0.001). Persistent monocyte levels ≥580 per μL during follow up were associated with further increase in risk of death (HR 1.52, 95% CI 1.10-2.11, p = 0.01) and MACE (HR 1.54, 95% CI 1.13-2.09, p = 0.006). Persistent monocyte levels ≥580 per μL during were associated with a significant increase in major bleeding events (HR 2.77, 95% CI 1.36-5.67, p = 0.005, after adjustment for HAS-BLED score).

Conclusion: High monocyte counts independently predict the occurrence of MACE, major bleeding and mortality, but not SSE. Understanding the pathophysiological mechanisms involved would help understand the relationships between monocytes, and adverse thrombotic and bleeding outcomes in AF patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200373PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051603PMC
January 2019

Predictors of diastolic dysfunction in ethnic groups: observations from the Hypertensive Cohort of The Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES).

J Hum Hypertens 2018 07 1;32(7):477-486. Epub 2018 May 1.

Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.

The study aimed to establish a relationship of ethnicity to diastolic dysfunction in subjects of African-Caribbean and South Asian origins and the impact of diastolic dysfunction and ethnicity on all-cause and cardiovascular mortality. Hypertensive subjects with ejection fraction ≥55% and no history of ischaemic heart disease/valve pathology (n  =  1546, 830 South Asians and 716 African-Caribbeans) were identified from the Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES). Diastolic function and cardiac remodelling were measured by echocardiography. African-Caribbean ethnicity was associated with lower prevalence of having diastolic dysfunction (odds ratio 0.67, 95% confidence interval 0.51-0.87, p  =  0.003) and increased left ventricular filling pressure (odds ratio 0.48, 95% confidence interval 0.34-0.69, p <  0.001) as well as lower left atrial index (p  <  0.001). This was the case despite the fact that African-Caribbean ethnicity was independently associated with higher left ventricular mass index (p   < 0.001). Ninety-two deaths (6%) occurred during 68  ±  21 months follow-up. On Cox regression analysis, South Asian ethnicity (p  =  0.024) was predictive of all-cause death before adjustment for parameters of diastolic dysfunction, but it was no longer predictive of death after accounting for these variables. South Asian ethnicity is independently associated with worse parameters of diastolic function in hypertension, despite African-Caribbeans having more prominent hypertrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41371-018-0064-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061936PMC
July 2018

Nitrite circumvents platelet resistance to nitric oxide in patients with heart failure preserved ejection fraction and chronic atrial fibrillation.

Cardiovasc Res 2018 08;114(10):1313-1323

Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Aims: Heart failure (HF) is a pro-thrombotic state. Both platelet and vascular responses to nitric oxide (NO) donors are impaired in HF patients with reduced ejection fraction (HFrEF) compared with healthy volunteers (HVs) due to scavenging of NO, and possibly also reduced activity of the principal NO sensor, soluble guanylate cyclase (sGC), limiting the therapeutic potential of NO donors as anti-aggregatory agents. Previous studies have shown that nitrite inhibits platelet activation presumptively after its reduction to NO, but the mechanism(s) involved remain poorly characterized. Our aim was to compare the effects of nitrite on platelet function in HV vs. HF patients with preserved ejection fraction (HFpEF) and chronic atrial fibrillation (HFpEF-AF), vs. patients with chronic AF without HF, and to assess whether these effects occur independent of the interaction with other formed elements of blood.

Methods And Results: Platelet responses to nitrite and the NO donor sodium nitroprusside (SNP) were compared in age-matched HV controls (n = 12), HFpEF-AF patients (n = 29), and chronic AF patients (n = 8). Anti-aggregatory effects of nitrite in the presence of NO scavengers/sGC inhibitor were determined and vasodilator-stimulated phosphoprotein (VASP) phosphorylation was assessed using western blotting. In HV and chronic AF, both nitrite and SNP inhibited platelet aggregation in a concentration-dependent manner. Inhibition of platelet aggregation by the NO donor SNP was impaired in HFpEF-AF patients compared with healthy and chronic AF individuals, but there was no impairment of the anti-aggregatory effects of nitrite. Nitrite circumvented platelet NO resistance independently of other blood cells by directly activating sGC and phosphorylating VASP.

Conclusion: We here show for the first time that HFpEF-AF (but not chronic AF without HF) is associated with marked impairment of platelet NO responses due to sGC dysfunction and nitrite circumvents the 'platelet NO resistance' phenomenon in human HFpEF, at least partly, by acting as a direct sGC activator independent of NO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvy087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054254PMC
August 2018

Impact of Mon2 monocyte-platelet aggregates on human coronary artery disease.

Eur J Clin Invest 2018 May 7;48(5):e12911. Epub 2018 Mar 7.

Institute of Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.

Background: Monocyte-platelet aggregates (MPAs) form when Mon1, Mon2 or Mon3 monocyte subsets adhere to platelets. They are pathophysiologically linked to coronary artery disease (CAD). However, their individual roles in the occurrence of diffuse CAD remain unknown.

Materials And Methods: Peripheral blood from 50 patients with diffuse CAD, 40 patients with focal CAD and 50 age-matched patients with normal coronary arteries was analysed by flow cytometry to quantify MPAs associated with individual monocyte subsets. Cutaneous forearm microcirculation was assessed using laser Doppler flowmetry at rest and after iontophoresis of acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) at 100 μA for 60 seconds. Patients with CAD had repeat assessment at 6 and 12 months.

Results: Baseline counts of MPAs with Mon2 subset (CD14++CD16+CC2+ monocytes) were significantly higher in patients with diffuse CAD compared to focal CAD (P = .001) and patients without CAD (P = .006). On multivariate regression, MPAs with Mon2 independently predicted diffuse CAD (odds ratio 1.10, 95% confidence interval 1.02-1.19, P = .01) and correlated negatively with endothelium-dependent microvascular vasodilation (r = -.37, P = .008), an association which persisted after adjustment for covariates. Longitudinal observation confirmed the persistence of an inverse relationship between MPAs with Mon2 and endothelium-dependent microvascular function.

Conclusion: Monocyte-platelet aggregates with Mon2 are increased in patients with diffuse CAD and therefore could represent an important contributor to accelerated coronary atherosclerotic progression by a mechanism involving microvascular endothelial dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eci.12911DOI Listing
May 2018

Role of Monocytes in Heart Failure and Atrial Fibrillation.

J Am Heart Assoc 2018 02 1;7(3). Epub 2018 Feb 1.

Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.117.007849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850261PMC
February 2018

Atrial Fibrillation and Hypertension.

Hypertension 2017 11 11;70(5):854-861. Epub 2017 Sep 11.

From the Institute of Cardiovascular Sciences, University of Birmingham, United Kingdom (M.S.D., A.S., E.S., G.Y.H.L.); Grodno State Medical University, Belarus (M.S.D.); and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.08934DOI Listing
November 2017

Guideline-Adherent Antithrombotic Treatment Improves Outcomes in Patients With Atrial Fibrillation: Insights From the Community-Based Darlington Atrial Fibrillation Registry.

Mayo Clin Proc 2017 08;92(8):1203-1213

Institute for Cardiovascular Sciences, University of Birmingham, Birmingham, UK. Electronic address:

Objective: To assess the influence of guideline-adherent vs nonadherent antithrombotic treatment (ATT) on stroke and mortality rates in an atrial fibrillation (AF) primary care population.

Patients And Methods: We used the Darlington Registry cohort, which included 105,000 patients from March 31, 2012, through March 31, 2013. Guideline adherence in ATT was assessed against 2014 National Institute for Health and Care Excellence guidelines, which recommend oral anticoagulation for stroke prevention as a default management unless a truly low risk of stroke (CHADS-VASc=0 in men and 1 in women) is evident.

Results: Of 2259 patients with AF (2.15%), 36.1% were undertreated, 50.8% were guideline adherent, and 13.1% were overtreated. Oral anticoagulation was declined by 5.0% and contraindicated in 8.3%. Of 67 incident strokes (3.0%), 66 (98.5%) occurred in high-risk patients (CHADS-VASc ≥2). For the high-risk cohort, 1-year stroke rates were 4.5% (95% CI, 3.2%-6.3%) for undertreatment, 1.9% (95% CI, 1.2%-2.9%) for guideline adherence, and 7.2% (95% CI, 4.4%-11.6%) for overtreatment; corresponding mortality rates were 16.1% (95% CI, 13.6%-19.0%), 8.0% (95% CI, 6.5%-9.8%), and 8.2% (95% CI, 5.2%-12.7%), respectively. On multivariable analysis, both undertreatment and overtreatment of high-risk patients were associated with significant increases in stroke rates (odds ratio [OR]=2.32; 95% CI, 1.30-3.14; P=.005 and OR=2.28; 95% CI, 1.12-4.63; P=.02, respectively). Undertreatment was also associated with a significant increase in all-cause mortality (OR=1.59; 95% CI, 1.14-2.21; P=.006).

Conclusion: Only half of all eligible patients with AF are prescribed oral anticoagulation in accordance with guideline recommendations. Guideline-adherent ATT significantly reduces the risk of stroke and improves survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mayocp.2017.05.023DOI Listing
August 2017

Secondary Versus Primary Stroke Prevention in Atrial Fibrillation: Insights From the Darlington Atrial Fibrillation Registry.

Stroke 2017 08 5;48(8):2198-2205. Epub 2017 Jul 5.

From the University of Birmingham Institute for Cardiovascular Sciences, City Hospital, United Kingdom (M.M., E.S., D.A.L., M.P., G.Y.H.L.); Department of Cardiology, Congenital Heart Diseases and Electrotherapy, Silesian Centre for Heart Diseases, Zabrze, Poland (M.M.); and Division of Family Practice, Chilliwack General Hospital, British Columbia, Canada (A.W.).

Background And Purpose: Although patients with atrial fibrillation (AF) who experienced an acute stroke are at high risk for recurrence, many patients are untreated or treated suboptimally for stroke prevention. The objective of this study is to compare clinical outcomes of AF patients with versus without previous stroke in relation to guideline-adherent antithrombotic treatment in a contemporary primary care population.

Methods: Community cohort of 105 000 patients from 11 general practices in Darlington, England, was used to assess AF stroke prevention strategies against 2014 National Institute for Health and Care Excellence guidelines.

Results: Overall, 2259 (2.15%) patients with AF were identified, of which 18.9% constituted a secondary prevention cohort. For secondary prevention, antithrombotic treatment was guideline adherent in 56.3%, 18.9% were overtreated, and 24.8% undertreated; corresponding proportions for primary prevention were 49.5%, 11.7%, and 38.8%, respectively. One-year stroke rates were 8.6% and 1.6% for secondary and primary prevention, respectively (<0.001); corresponding all-cause mortality rates were 9.8% and 9.4%, respectively (=0.79). On multivariable analysis, lack of antithrombotic treatment guideline adherence was associated with increased stroke risk for primary prevention (odds ratio, 2.95; 95% confidence interval, 1.26-6.90; =0.013 for undertreatment); for secondary prevention, lack of guideline adherence was associated with increased risk of recurrent stroke (odds ratio, 2.80; 95% confidence interval, 1.25-6.27; =0.012 for overtreatment) and all-cause death (odds ratio, 2.75; 95% confidence interval, 1.33-5.69; =0.006 for undertreatment).

Conclusions: Only approximately half of eligible patients with AF are prescribed oral anticoagulation in line with guidelines. Guideline-adherent antithrombotic treatment significantly reduces the risk of stroke among primary prevention patients and both risk of recurrent stroke and death in patients with previous stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.116.016146DOI Listing
August 2017

Predictors of 5-year outcomes in malignant phase hypertension: the West Birmingham Malignant Hypertension Registry.

J Hypertens 2017 11;35(11):2310-2314

Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.

Objective: Malignant hypertension represents a high-risk condition and there are scarce data on current clinical patterns of this condition. The aim of the study is to identify the clinical and demographic factors associated with poor outcome.

Methods: The data collected from 1958 to May 2016 included a total of 351 patients whose 5-year survival status was known: 221 white Caucasians (63%, age 51 ± 13 years, 64% male), 83 African-Caribbeans (24%, 45 ± 11 years, 61% male), and 47 South Asians (13%, 42 ± 11 years, 74% male).

Results: During the 5-year follow-up 119 (34%) patients suffered a primary outcome, defined as the composite endpoint of death or dialysis. The 5-year mortality ranged from 76% in patients diagnosed before 1967 to 7% in patients diagnosed between 1997 and 2006. The independent predictors of outcome were advanced age (vs. a reference group of < 40-year-old; P = 0.01 for age at presentation 51-60 years, P < 0.001 for age > 60 years), prior use of antihypertensive medications (P = 0.002), higher serum creatinine (P = 0.006), and proteinuria (P < 0.01). Also, white Caucasian (odds ratio12.02, 95% confidence interval 1.64-88.15, P = 0.01) and African-Caribbean (odds ratio 15.55, 95% confidence interval 2.06-117.29, P = 0.008) origins were associated with higher mortality vs. South Asians. The years of the diagnosis after 1977 were significantly associated with lower composite endpoint of death or dialysis, all P < 0.01.

Conclusion: There has been a major improvement in 5-year survival in patients with malignant hypertension over recent decades. Abnormal renal function at presentation still predicts worse outcome. South Asian ethnicity is also associated with better outcome, although mechanisms involved are yet to be established.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000001446DOI Listing
November 2017

Is echocardiography valid and reproducible in patients with atrial fibrillation? A systematic review.

Europace 2017 Sep;19(9):1427-1438

University of Birmingham Institute of Cardiovascular Sciences, Birmingham, UK.

Aims: Echocardiography is vital in the routine assessment and management of atrial fibrillation (AF). We performed a systematic review of the validity and reproducibility of echocardiographic left ventricular systolic and diastolic function in AF, and optimal acquisition methods.

Methods And Results: Online databases were searched for studies in patients with AF at the time of echocardiography (1960 to August 2015), prospectively registered with PROSPERO (CRD42015025297). The systematic review included 32 studies from 3 066 search results (1 968 patients with AF). Average age was 67 years, 33% were women, mean LVEF 53% (±10%), and average E/e' 11.7 (±2.7). Data on the validity and reproducibility of systolic indices were extremely limited. In contrast, diastolic parameters demonstrated correlation with invasive filling pressure and adequate reproducibility: E/e' (n = 444) r = 0.47 to 0.79; IVRT (n = 177) r = -0.70 to -0.95; E/Vp` (n = 55) r = 0.63 and 0.65; pulmonary vein diastolic flow (n = 67) r = -0.80 and -0.91. Elevated E/e' (>15) was associated with functional capacity, quality of life, and impaired prognosis. For optimal acquisition in AF patients, cardiac cycles with controlled heart rate (<100 beats/min) and similar preceding and pre-preceding RR intervals are required. Cardiac cycle length and equivalence were more important than the number of beats averaged.

Conclusion: With careful selection of appropriate cardiac cycles, echocardiography is a valid tool to identify diastolic dysfunction in AF, and E/e' is an independent marker of clinical status and adverse prognosis. However, data on systolic function was extremely limited and requires further prospective study and assessment of variability in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/eux027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834126PMC
September 2017

Clinical Features and Prognosis in Patients with Atrial Fibrillation and Prior Stroke: Comparing the Fushimi and Darlington AF Registries.

EBioMedicine 2017 Apr 16;18:199-203. Epub 2017 Mar 16.

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

Background: Ethnic differences in clinical characteristics, stroke risk profiles and outcomes among atrial fibrillation (AF) patients may exist. We therefore compared AF patients with previous stroke from Japan and the United Kingdom (UK).

Methods: We compared clinical characteristics, stroke risk and outcomes among AF patients from the Fushimi AF registry who had experienced a previous stroke (Japan; n=688; 19.7%) and the Darlington AF registry (UK; n=428; 19.0%).

Results: AF patients with previous stroke in Fushimi were significantly younger (76.8 and 79.6years of age in Fushimi and Darlington; p<0.01) with a lower proportion of females (37.4% vs. 45.1%; p=0.01) than those from Darlington. Although the CHADS-VASc score was lower in AF patients in Fushimi than those in Darlington (5.18 vs. 5.57; p<0.01), oral anticoagulation (OAC) was prescribed significantly more frequently in Fushimi (68.3%) than Darlington (61.7%) (p=0.02). Multivariate logistic regression analysis showed that Japanese ethnicity was associated with a significantly decreased risk of recurrent stroke (OR 0.59. 95% CI 0.36-0.97; p=0.04) but a significantly increased risk of all-cause mortality (OR 1.76, 95% CI 1.18-2.66; p<0.01) in AF patients with previous stroke.

Conclusions: AF patients with previous stroke in the UK were at higher risk of recurrent stroke compared to Japanese patients, but OAC was utilised less frequently. There was a lower risk of recurrent stroke in the secondary prevention cohort from the Fushimi registry, but an increased risk of all-cause mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2017.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405156PMC
April 2017

Recent advances in the understanding and management of atrial fibrillation: a focus on stroke prevention.

F1000Res 2016 20;5:2887. Epub 2016 Dec 20.

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

Atrial fibrillation (AF) is associated with an increased risk of stroke compared with the general population. It is anticipated that by 2030 an estimated 14-17 million patients will be diagnosed with this most prevalent arrhythmia within the European Union. AF-related stroke confers a higher mortality and morbidity risk, and thus early detection and assessment for the initiation of effective stroke prevention with oral anticoagulation (OAC) is crucial. Recent guidelines point to the use of non-vitamin K antagonist OACs (NOACs) where appropriate in stroke prevention of patients with non-valvular AF. At present, there are four NOACS available, with no direct head-to-head comparisons to suggest the superiority of one drug over another. Simple and practical risk assessment tools have evolved over the years to facilitate stroke and bleeding risk assessment in busy clinics and wards to aid decision-making. At present, the CHA DS VASc (congestive heart failure, hypertension, age 65-74/>75, diabetes mellitus, stroke/transient ischemic attack/thromboembolism, vascular disease, female sex) score is recommended by many international guidelines as a simple and practical method of assessing stroke risk in such patients. Alongside this, use of the HAS BLED (hypertension systolic blood pressure >160 mmHg, abnormal liver/renal function [with creatinine ≥200 μmol/L], stroke, bleeding history or predisposition, labile international normalized ratio [range <60% of the time], elderly [>65], concomitant drugs/alcohol) score aims to identify patients at high risk of bleeding for more regular review and follow-up and draws attention to potentially reversible bleeding risk factors. The aim of this review article is to provide an overview of recent advances in the understanding and management of AF with a focus on stroke prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/f1000research.10176.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224684PMC
December 2016

Premature Cardiac Aging in South Asian Compared to Afro-Caribbean Subjects in a Community-Based Screening Study.

J Am Heart Assoc 2016 11 10;5(11). Epub 2016 Nov 10.

University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK.

Background: People of South Asian (SAs) and African Caribbean (AC) origin have increased cardiovascular morbidity, but underlying mechanisms are poorly understood. Aging is the key predictor of deterioration in diastolic function, which can be assessed by echocardiography using E/e' ratio as a surrogate of left ventricular (LV) filling pressure. The study aimed to assess a possibility of premature cardiac aging in SA and AC subjects.

Methods And Results: We studied 4540 subjects: 2880 SA and 1660 AC subjects. All participants underwent detailed echocardiography, including LV ejection fraction, average septal-lateral E/e', and LV mass index (LVMI). When compared to ACs, SAs were younger, with lower mean LVMI, systolic blood pressure (BP), diastolic BP, and body mass index (BMI), as well as a lower prevalence of hypertension and smoking (P≤0.001 for all). In a multivariate linear regression model including age, sex, ethnicity, BP, heart rate, BMI, waist circumference, LVMI, history of smoking, hypertension, coronary artery disease, diabetes mellitus, medications, SA origin was independently associated with higher E/e' (regression coefficient±standard error, -0.66±0.10; P<0.001, adjusted R for the model 0.21; P<0.001). Furthermore, SAs had significantly accelerated age-dependent increase in E/e' compared to ACs. On multivariable Cox regression analysis without adjustment for E/e', SA ethnicity was independently predictive of mortality (P=0.04). After additional adjustment for E/e', the ethnicity lost its significance value, whereas E/e' was independently predictive of higher risk of death (P=0.008).

Conclusions: Premature cardiac aging is evident in SAs and may contribute to high cardiovascular morbidity in this ethnic group, compared to ACs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.116.004110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210345PMC
November 2016

Current Understanding of Atherogenesis.

Am J Med 2017 Mar 23;130(3):268-282. Epub 2016 Nov 23.

Department of Medicine, University of Birmingham Institute of Cardiovascular Sciences, City Hospital, United Kingdom; Cardiology Department at Sandwell and West Birmingham Hospitals NHS Trust, City Hospital and Sandwell Hospital, West Bromwich, United Kingdom. Electronic address:

Scientific understanding of atherogenesis is constantly developing. From Virchow's observations 160 years ago we now recognize the endothelial response to injury as inflammatory, involved in all stages of atherosclerosis. Endothelial activation may cause reversible injury or dysfunction, or lead to irreparable damage. Indeed, early atherosclerosis is reversible. The introduction of genome-wide association testing has furthered the identification of potentially important genetic variants that help explain the heritability of coronary artery disease as well as spontaneous cases of severe coronary artery disease in patients with otherwise minimal risk factors. However, the mechanisms by which many of the newer variants exert their influence remain unknown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2016.10.022DOI Listing
March 2017

IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design of the IMPRESS-AF randomised controlled trial.

BMJ Open 2016 10 5;6(10):e012241. Epub 2016 Oct 5.

University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK.

Introduction: Patients with atrial fibrillation frequently suffer from heart failure with preserved ejection fraction. At present there is no proven therapy to improve physical capacity and quality of life in participants with permanent atrial fibrillation with preserved left ventricular contractility.

Objective: The single-centre IMproved exercise tolerance In heart failure With PReserved Ejection fraction by Spironolactone On myocardial fibrosiS In Atrial Fibrillation (IMPRESS-AF) trial aims to establish whether treatment with spironolactone as compared with placebo improves exercise tolerance (cardiopulmonary exercise testing), quality of life and diastolic function in patients with permanent atrial fibrillation.

Methods And Analysis: A total of 250 patients have been randomised in this double-blinded trial for 2-year treatment with 25 mg daily dose of spironolactone or matched placebo. Included participants are 50 years old or older, have permanent atrial fibrillation and ejection fraction >55%. Exclusion criteria include contraindications to spironolactone, poorly controlled hypertension and presence of severe comorbidities with life expectancy <2 years. The primary outcome is improvement in exercise tolerance at 2 years and key secondary outcomes include quality of life (assessed using the EuroQol EQ-5D-5L (EQ-5D) and Minnesota Living with Heart Failure (MLWHF) questionnaires), diastolic function and all-cause hospitalisation.

Ethics And Dissemination: The study has been approved by the National Research and Ethics Committee West Midlands-Coventry and Warwickshire (REC reference number 14/WM/1211). The results of the trial will be published in an international peer-reviewed journal.

Trial Registration Numbers: EudraCT2014-003702-33; NCT02673463; Pre-results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2016-012241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073497PMC
October 2016

Non-vitamin K oral anticoagulants versus vitamin K antagonists in the treatment of venous thromboembolic disease.

Expert Opin Pharmacother 2016 Oct;17(15):2033-47

a University of Birmingham Institute of Cardiovascular Sciences , City Hospital , Birmingham , UK.

Introduction: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the western world. The approval of non-vitamin K oral anticoagulants (NOACs) as antithrombotic alternatives to vitamin K antagonists (VKAs) has offered more treatment options to physicians for the prevention of VTE recurrence, fatal pulmonary embolism (PE) and long-term complications. Four NOACs (dabigatran, rivaroxaban, apixaban and edoxaban) that have been approved for the treatment of acute VTE following large phase III trials, where NOACs demonstrated similar efficacy and superior safety profile compared to VKAs.

Areas Covered: The purpose of this review article is to summarise current knowledge of oral anticoagulation for the treatment of acute VTE and to compare NOACs with VKAs, highlighting the factors that might influence the decisions of physicians. Data for this article were obtained through a search of PubMed for trials comparing NOACs with VKAs in acute VTE setting and articles or analyses that interpreted results from these trials.

Expert Opinion: The NOACs have changed clinical practice regarding oral anticoagulation for acute VTE. Despite their advantages, 'grey zones' still remain and more studies are needed to provide evidence and confirm the superiority (or at least non-inferiority) of NOACs over VKAs. Real world data might give additional insights.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14656566.2016.1232393DOI Listing
October 2016

Antiplatelet versus anticoagulation treatment for patients with heart failure in sinus rhythm.

Cochrane Database Syst Rev 2016 Sep 15;9:CD003333. Epub 2016 Sep 15.

University of Birmingham, Institute of Cardiovascular Sciences, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK, B18 7QH.

Background: Morbidity in patients with chronic heart failure is high, and this predisposes them to thrombotic complications, including stroke and thromboembolism, which in turn contribute to high mortality. Oral anticoagulants (e.g. warfarin) and antiplatelet agents (e.g. aspirin) are the principle oral antithrombotic agents. Many heart failure patients with sinus rhythm take aspirin because coronary artery disease is the leading cause of heart failure. Oral anticoagulants have become a standard in the management of heart failure with atrial fibrillation. However, a question remains regarding the appropriateness of oral anticoagulants in heart failure with sinus rhythm. This update of a review previously published in 2012 aims to address this question.

Objectives: To assess the effects of oral anticoagulant therapy versus antiplatelet agents for all-cause mortality, non-fatal cardiovascular events and risk of major bleeding in adults with heart failure (either with reduced or preserved ejection fraction) who are in sinus rhythm.

Search Methods: We updated the searches in September 2015 on CENTRAL (The Cochrane Library), MEDLINE and Embase. We searched reference lists of papers and abstracts from cardiology meetings and contacted study authors for further information. We did not apply any language restrictions. Additionally, we searched two clinical trials registers: ClinicalTrials.gov (www.ClinicalTrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal apps.who.int/trialsearch/) (searched in July 2016).

Selection Criteria: We included randomised controlled trials comparing antiplatelet therapy versus oral anticoagulation in adults with chronic heart failure in sinus rhythm. Treatment had to last at least one month. We compared orally administered antiplatelet agents (aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor, dipyridamole) versus anticoagulant agents (coumarins, warfarin, non-vitamin K oral anticoagulants).

Data Collection And Analysis: Two review authors independently assessed trials for inclusion and assessed the risks and benefits of antithrombotic versus antiplatelet therapy using relative measures of effects, such as risk ratios (RR), accompanied with 95% confidence intervals (CI). The data extracted included data relating to the study design, patient characteristics, study eligibility, quality, and outcomes. We used GRADE criteria to assess the quality of the evidence.

Main Results: This update identified one additional study for inclusion, adding data for 2305 participants. This addition more than doubled the overall number of patients eligible for the review. In total, we included four randomised controlled trials (RCTs) with a total of 4187 eligible participants. All studies compared warfarin with aspirin. One RCT additionally compared warfarin with clopidogrel. All included RCTs studied patients with heart failure with reduced ejection fraction.Analysis of all outcomes for warfarin versus aspirin was based on 3663 patients from four RCTs. All-cause mortality was similar for warfarin and aspirin (RR 1.00, 95% CI 0.89 to 1.13; 4 studies; 3663 participants; moderate quality evidence). Oral anticoagulation was associated with a reduction in non-fatal cardiovascular events, which included non-fatal stroke, myocardial infarction, pulmonary embolism, peripheral arterial embolism (RR 0.79, 95% CI 0.63 to 1.00; 4 studies; 3663 participants; moderate quality evidence). The rate of major bleeding events was twice as high in the warfarin groups (RR 2.00, 95% CI 1.44 to 2.78; 4 studies; 3663 participants; moderate quality evidence). We generally considered the risk of bias of the included studies to be low.Analysis of warfarin versus clopidogrel was based on a single RCT (N = 1064). All-cause mortality was similar for warfarin and clopidogrel (RR 0.93, 95% CI 0.72 to 1.21; 1 study; 1064 participants; low quality evidence). There were similar rates of non-fatal cardiovascular events (RR 0.85, 95% CI 0.50 to 1.45; 1 study; 1064 participants; low quality evidence). The rate of major bleeding events was 2.5 times higher in the warfarin group (RR 2.47, 95% CI 1.24 to 4.91; 1 study; 1064 participants; low quality evidence). Risk of bias for this study can be summarised as low.

Authors' Conclusions: There is evidence from RCTs to suggest that neither oral anticoagulation with warfarin or platelet inhibition with aspirin is better for mortality in systolic heart failure with sinus rhythm (high quality of the evidence for all-cause mortality and moderate quality of the evidence for non-fatal cardiovascular events and major bleeding events). Treatment with warfarin was associated with a 20% reduction in non-fatal cardiovascular events but a twofold higher risk of major bleeding complications (high quality of the evidence). We saw a similar pattern of results for the warfarin versus clopidogrel comparison (low quality of the evidence). At present, there are no data on the role of oral anticoagulation versus antiplatelet agents in heart failure with preserved ejection fraction with sinus rhythm. Also, there were no data from RCTs on the utility of non-vitamin K antagonist oral anticoagulants compared to antiplatelet agents in heart failure with sinus rhythm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD003333.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457803PMC
September 2016

Use of non-vitamin K antagonist oral anticoagulants in patients with heart failure and atrial fibrillation: does concomitant kidney disease change our practice?

Eur J Heart Fail 2016 09;18(9):1172-4

University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.552DOI Listing
September 2016

Effects of non-vitamin K antagonist oral anticoagulants on fibrin clot and whole blood clot formation, integrity and thrombolysis in patients with atrial fibrillation.

J Thromb Thrombolysis 2016 Nov;42(4):535-44

Institute for Cardiovascular Sciences, City Hospital, University of Birmingham, Dudley Road, Birmingham, B18 7QH, UK.

Non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin and heparins in several clinical situations. With varying modes of action, the effects of NOACs on thrombus formation, integrity, and lysis is unknown. To determine whether two techniques of thrombelastography (TEG) and a micro-plate assay (MPA) provide novel data on thrombus formation, integrity and lysis in those taking a NOACs compared to warfarin and a control group taking aspirin. We assessed thrombogenesis, clot integrity and fibrinolysis in blood (TEG) and plasma (MPA) from 182 atrial fibrillation patients-50 on aspirin, 50 on warfarin, and 82 on a NOAC (17 apixaban, 19 dabigatran and 46 rivaroxaban). Eleven of 16 TEG indices and 4 of 5 MPA indices differed (p ≤ 0.01) between those on aspirin, warfarin or a NOAC. Three TEG indices and 4 MPA indices differed (p < 0.01) between the NOACs. Time to initiation of clot formation was most rapid on apixaban, then rivaroxaban and slowest on dabigatran. The rate of clot formation was most rapid on dabigatran, then apixaban, and slowest on rivaroxaban. Clot density was greatest on rivaroxaban, then apixaban, but weakest on dabigatran. The rate of clot dissolution was most rapid in apixaban, then dabigatran, and slowest on rivaroxaban. The TEG and MPA identify major differences in thrombogenesis and fibrinolysis in different NOACs. These techniques may have value in investigating the effects of these drugs on haemostasis in a clinical setting, and in identifying those in need of targeted therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-016-1399-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040730PMC
November 2016