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Endogenous fibrinolysis is a powerful natural defense mechanism against lasting arterial thrombotic occlusion. Recent prospective studies have shown that impaired endogenous fibrinolysis (or hypofibrinolysis) can be detected in a significant number of patients with acute coronary syndrome (ACS) using global assays and is a strong marker of future cardiovascular risk. This novel risk biomarker is independent of traditional cardiovascular risk factors and unaffected by antiplatelet therapy. Most prospective prognostic data have been obtained using a global assay using native whole blood at high shear or plasma turbidimetric assays, which are described herein. Tests of endogenous fibrinolysis could be used to identify patients with ACS who, despite antiplatelet therapy, remain at high cardiovascular risk. This review discusses the impact of currently available medications and those in development that favorably modulate fibrinolytic status and may offer a potential new avenue to improve outcomes in ACS. [ABSTRACT FROM AUTHOR]

Background: When assessing ischemic stroke risk in patients with atrial fibrillation (AF), the CHA2DS2-VASc score is calculated based on the baseline risk factors, and the outcomes are determined after a follow-up period. However, the stroke risk in patients with AF does not remain static, and with time, patients get older and accumulate more comorbidities.Objectives: This study hypothesized that the "Delta CHA2DS2-VASc score," which reflects the change in score between baseline and follow-up, would be more predictive of ischemic stroke compared with the baseline CHA2DS2-VASc score.Methods: A total of 31,039 patients with AF who did not receive antiplatelet agents or oral anticoagulants, and who did not have comorbidities of the CHA2DS2-VASc score except for age and sex, were studied. The Delta CHA2DS2-VASc scores were defined as the differences between the baseline and follow-up CHA2DS2-VASc scores. During 171,956 person-years, 4,103 patients experienced ischemic stroke. The accuracies of baseline, follow-up, and Delta CHA2DS2-VASc scores in predicting ischemic stroke were analyzed and compared.Results: The mean baseline CHA2DS2-VASc score was 1.29, which increased to 2.31 during the follow-up, with a mean Delta CHA2DS2-VASc score of 1.02. The CHA2DS2-VASc score remained unchanged in only 40.8% of patients. Among 4,103 patients who experienced ischemic stroke, 89.4% had a Delta CHA2DS2-VASc score ≥1 compared with only 54.6% in patients without ischemic stroke, and 2,643 (64.4%) patients had ≥1 new-onset comorbidity, the most common being hypertension. The Delta CHA2DS2-VASc score was a significant predictor of ischemic stroke that performed better than baseline or follow-up CHA2DS2-VASc scores, as assessed by the C-index and the net reclassification index.Conclusions: In this AF cohort, the authors demonstrated that the CHA2DS2-VASc score was not static, and that most patients with AF developed ≥1 new stroke risk factor before presentation with ischemic stroke. The Delta CHA2DS2-VASc score, reflecting the change in score between baseline and follow-up, was strongly predictive of ischemic stroke, reflecting how stroke risk in AF is a dynamic process due to increasing age and incident comorbidities. [ABSTRACT FROM AUTHOR]

Purpose Qualitative research on atrial fibrillation (AF) patient's experiences and perceptions of taking the non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention is limited. This study explores patients' experiences of dabigatran and their recommendations for development of educational materials. Patients and methods Semi-structured individual interviews with 8 warfarin-naive and 8 warfarin-experienced AF patients, using qualitative deductive thematic analysis. Results The four main overarching themes included: understanding the diagnosis; reaching a treatment decision; challenges of living with OAC; and patient perceptions of treatment. Patients discussed their shock of diagnosis, and seeking information and support at that time. Narratives suggest patients preferred to be led by the doctor when making treatment decisions, and would often compare dabigatran to warfarin. Patients reported side-effects and challenges with both treatment options, and discussed their beliefs surrounding medications, including misconceptions. In addition to the original framework, two further themes were added: challenges of living with AF, and patient recommendations. Generally patients found AF symptoms distressing, which impacted their quality of life. Patient recommendations included the content and delivery of educational materials and development of tools to help with their understanding of AF and anticoagulation, as well as treatment adherence and anxiety surrounding symptoms and side effects. Conclusion Patient recommendations emphasised the need for interventions to relieve anxiety surrounding the diagnosis and possible treatment side effects. Tailored ‘disease-specific’ support is essential to ensure efficacious treatment. This qualitative study highlights the need for patient involvement in the development of educational materials and resources for patients commencing treatment with NOACs. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) confers increased risk of stroke and other thromboembolic events, and oral anticoagulation therefore is the essential part of AF management to reduce the risk of these complications. Until recently, the vitamin K antagonists (VKAs, e.g., warfarin) were the only oral anticoagulants available, acting by decreased synthesis of vitamin K-dependent coagulation factors (II, VI, IX, and X). The VKAs had many limitations: delayed onset and prolonged offset of action, variability of anticoagulant effect among patients, multiple food and drug interactions affecting pharmacological properties of warfarin, narrow therapeutic window, and obligatory regular laboratory control, which all made warfarin "inconvenient" both for patients and clinicians. The limitations of VKAs led to development of a new class of drugs collectively defined as non-VKA oral anticoagulants (NOACs), which included direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban). The NOACs avoid many of the VKA drawbacks. In this review, we will focus on the current evidence justifying the use of NOACs in non-valvular AF. [ABSTRACT FROM AUTHOR]

Non-vitamin K antagonist oral anticoagulants (NOACs) have changed the landscape for stroke prevention in atrial fibrillation (AF). Given the huge burden of AF in Asians, more attention to stroke prevention is clearly needed. Aiming to provide an overview and reappraisal of stroke prevention in Asians with AF, we searched MEDLINE for information on NOACs in Asians. In addition, abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. In the 4 recent Phase 3 trials comparing NOACs to warfarin, a consistent pattern is evident. For efficacy endpoints in the comparison of NOACs vs warfarin, a significant reduction in stroke/systemic embolization was seen for dabigatran 150 mg [HR 0.45 (0.28-0.72)], with non-significant trends seen for lower stroke/systemic embolization with other NOACs, except edoxaban 30 mg. A similar pattern was seen for ischaemic stroke, with a significant reduction for dabigatran 150 mg [HR 0.55 (0.32-0.950]. For haemorrhagic stroke, all NOAC regimes, except rivaroxaban 20 mg, had significantly lower hazard ratios. No evidence of increased myocardial infarction was found for NOACs. All-cause mortality was significantly lowered amongst Asian patients on edoxaban 60 mg compared to warfarin [HR 0.63 (0.40-0.98)] with non-significant trends to lower mortality with dabigatran 150 mg, rivaroxaban and edoxaban 30 mg. For safety endpoints, all the NOAC regimes, except rivaroxaban 20 mg, significantly reduced major bleeding and 'all bleeding' events. Intracranial haemorrhage was consistently lowered by all NOACs. None of NOACs increased gastrointestinal bleeding. These information suggested that NOACs should be preferentially indicated for stroke prevention in Asians with AF. [ABSTRACT FROM AUTHOR]

• Appropriate management of AF patients with cancer in real-world clinical practice is challenging. • In this EORP-AF study, we analyzed a cohort of AF patients with prior or active cancer. • A structured approach based on the "Atrial fibrillation Better Care" (ABC) Pathway is still suboptimal. • Adherence to the "C" criterion (i.e. management of comorbidities) was more critical, being specifically lower in cancer patients. • Adherence to the ABC pathway was independently associated with a lower risk outcomes. Implementation of the Atrial fibrillation Better Care (ABC) pathway is recommended by guidelines on atrial fibrillation (AF), but the impact of adherence to ABC pathway in patients with cancer is unknown. To investigate the adherence to ABC pathway and its impact on adverse outcomes in AF patients with cancer. Patients enrolled in the EORP-AF General Long-Term Registry were analyzed according to (i) No Cancer; and (ii) Prior or active cancer and stratified in relation to adherence to the ABC pathway. The composite Net Clinical Outcome (NCO) of all-cause death, major adverse cardiovascular events and major bleeding was the primary endpoint. Among 6550 patients (median age 69 years, females 40.1%), 6005 (91.7%) had no cancer, while 545 (8.3%) had a diagnosis of active or prior cancer at baseline, with the proportions of full adherence to ABC pathway of 30.6% and 25.7%, respectively. Adherence to the ABC pathway was associated with a significantly lower occurrence of the primary outcome vs. non-adherence, both in 'no cancer' and 'cancer' patients [adjusted Hazard Ratio (aHR) 0.78, 95% confidence interval (CI): 0.66–0.92 and aHR 0.59, 95% CI 0.37–0.96, respectively]. Adherence to a higher number of ABC criteria was associated with a lower risk of the primary outcome, being lowest when 3 ABC criteria were fulfilled (no cancer: aHR 0.54, 95%CI: 0.36–0.81; with cancer: aHR 0.32, 95% CI 0.13–0.78). In AF patients with cancer enrolled in the EORP-AF General Long-Term Registry, adherence to ABC pathway was sub-optimal. Full adherence to ABC-pathway was associated with a lower risk of adverse events [Display omitted] Adherence to the "Atrial fibrillation Better Care" (ABC) pathway in patients with atrial fibrillation and cancer and its impact on clinical outcomes. [ABSTRACT FROM AUTHOR]

We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of =2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin. [ABSTRACT FROM AUTHOR]

Aims We assessed changes of serum combined free immunoglobulin light chains (cFLC) levels, which are associated with increased all-cause mortality, in ST-elevation myocardial infarction (STEMI) in relation to inflammation and renal function indices. Methods cFLC were measured in 48 patients with STEMI on days 1, 3, 7 and 30 with assessment of their relationships with monocyte subsets, high sensitivity C-reactive protein (hsCRP), and cystatin C. Day 1 levels in STEMI patients were compared to 40 patients with stable coronary artery disease, and 37 healthy controls. Results There were no significant differences in cFLC levels between the study groups. In STEMI patients, cFLC values peaked on day 7 post-MI and remained elevated on day 30 (p < 0.001 vs. day 1 for both). hsCRP concentrations peaked on day 3 of STEMI followed by their gradual reduction to the levels seen in the controls (p < 0.001). In STEMI cFLC correlated with cystatin C (r = 0.55, p < 0.001), and negatively correlated with counts of CD14++CD16- monocytes (r = -0.55, p < 0.001). On multivariate Cox regression analysis, cFLC concentrations were associated with increased need for future percutaneous coronary intervention (PCI) (p = 0.019). Conclusion cFLC levels increase during STEMI with peak values on day 7 after presentation and predict the need for future PCI. [ABSTRACT FROM AUTHOR]

Introduction The mental health prognosis following a venous thromboembolism in youth has not been investigated comprehensively. Using psychotropic drug purchase as a proxy for mental health status, we investigated this issue in a large cohort of young incident venous thromboembolism patients. Methods Using Danish nationwide administrative registries from the period 1997-2010, we identified 4,132 patients aged 13-33 years with a first-time venous thromboembolism diagnosis and no history of psychotropic drug usage. We sampled comparison cohort of random general population controls, matched individually in a 1:5 ratio based on sex and birth year. Participants were followed in prescription purchase registries for their first psychotropic drug purchase. Results Among young venous thromboembolism case cases, the 1-year risk of psychotropic drug purchase was 7.1% (95% confidence interval [CI] 6.3, 7.9) and the 5-year risk 22.1% (95% CI 20.7, 23.5). This was substantially higher than among population controls, with 1- and 5-year risk differences relative to the controls of 4.7% (95% CI 3.9, 5.5), and 10.8% (95% CI 9.4, 12.3), respectively. Adjustment for the effects of recent pregnancy or somatic provocations attenuated risk differences to 4.1% (95% CI 3.5, 5.1) after 1 year and 9.6% (95% CI 8.3, 11.2) after 5 years. Conclusions A venous thromboembolism diagnosis in youth is associated with a poorer mental health prognosis: one in five patients are prescribed psychotropic medication within the first 5 year after diagnosis. Highlights • VTE in the young is associated with a poor mental health prognosis • 1 in 5 patients purchase psychotropic drugs within 5 years after VTE diagnosis • Among similarly aged peers, only 1 in 10 purchase psychotropics in the same period • Young VTE patients may need long-term followup with a focus on mental health. [ABSTRACT FROM AUTHOR]

Background Current clinical guidelines recommend that risk stratification for ischaemic stroke in patients with nonvalvular AF (NVAF) should be performed using the CHA2DS2-VASc score (Congestive heart failure, Hypertension, Age ≥ 75 years [double], Diabetes mellitus, previous thromboembolism [double], Vascular disease, Age 65-74 years, and female gender) to aid decision making for antithrombotic treatment, with a preference for Non-Vitamin K Oral Anticoagulants (NOACs) in those with CHA2DS2-VASc score ≥ 1. However, CHA2DS2-VASc score is not recommended in the 2014 Japanese Circulation Society (JCS) guidelines for patients with NVAF. Methods To assess the impact of the JCS approach to stroke prevention in AF, and model the impact of using a CHA2DS2-VASc based 2-step decision making strategy, we calculated the incidence of ischaemic stroke in NVAF patients without OAC on basis of the CHADS2 and CHA2DS2-VASc scores using published Japanese data, and estimated the preventable number of stroke events. Results Using a CHA2DS2-VASc-based approach, the potential annual stroke events based on the estimated total number of NVAF patients in Japan was 889,000, as follows: 4369 for dabigatran 150 mg, 6049 for dabigatran 110 mg, 5918 for rivaroxaban (intention-to-treat; ITT), 5302 for apixaban, 5843 for edoxaban 60 mg (ITT), and 7598 for edoxaban 30 mg (ITT), respectively. Using a CHADS2 score-based approach, the number of potential stroke events was much greater for each agent. Conclusion Our modelling analysis has shown that when considering antithrombotic treatment for Japanese NVAF patients, using a CHA2DS2-VASc-based approach would allow greater opportunities for stroke prevention. [ABSTRACT FROM AUTHOR]

• Amongst AF patients with long term use (≥1 year) of mHealth technology for optimising stroke prevention, symptom control and comorbidity management, there was a reduced risk for the composite outcome of 'ischaemic stroke/systemic thromboembolism, death, and rehospitalization' in patients using App-based management based on the ABC (Atrial fibrillation Better Care) pathway. • Rates of clinical outcomes (thromboembolism, bleeding events, recurrent atrial fibrillation and its symptoms, heart failure, and rehospitalization) were lower in patients allocated to mAF App intervention, compared with usual care. • Over 70% of patients using the mAF App had adherence of approximately 70%, with the overall persistence of mAFA use being 91.7%. Background. In the mobile Atrial Fibrillation App (mAFA)-II trial, the use of mobile health (mHealth) technology, incorporating AF screening and integrated management strategy, was associated with improved short-term clinical outcomes. The aim of this study was to report adherence/persistence and long term (≥1 year) clinical outcomes of the mAFA-II trial, with mHealth-supported optimised stroke prevention, symptom control and comorbidity management. Methods. We studied an adult population screened for AF, where identified patients could enter a structured program of holistic and integrated care based on the ABC (Atrial fibrillation Better Care) pathway using mHealth with a mAFA intervention. In this cluster randomised trial, comparing mHeath intervention to usual care, the primary composite outcome was 'stroke/thromboembolism, all-cause death and rehospitalization'. Results. The 1261 subjects (mean age 67.0 years, 38.0% female) who were followed up over one year (mean follow-up 687 (standard deviation, SD 191) days) in the intervention arm, had a lower risk of the composite outcome of 'ischaemic stroke/systemic thromboembolism, death, and rehospitalization' (hazard ratio, HR 0.18, 95% confidence interval, CI: 0.13–0.25, P < 0.001), compared to usual care (1212 subjects, mean age 70.1 years, 42.1% female). Of 842 patients using their smart devices for 'Better symptom management', 70.8% had good management adherence (monitoring time/follow-up since initial monitoring ≥ 70%), with the persistence of use of 91.7%. Conclusion. Amongst AF patients with long term use (≥1 year) of mHealth technology for optimising stroke prevention, symptom control and comorbidity management, adherence/persistence was good and associated with a reduction in adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Most patients with atrial fibrillation (AF) and risk factors for stroke require oral anticoagulation (OAC) to decrease the risk of stroke or systemic embolism. This is now best achieved with direct oral anticoagulants that decrease the risk of intracranial bleeding compared with vitamin K antagonists. Of note, approximately 5% to 10% of patients undergoing percutaneous coronary intervention have AF, which complicates antithrombotic therapy in daily practice, because the guidelines recommend that these patients also receive dual antiplatelet therapy (DAPT) to reduce the risk of ischemic complications. However, combining OAC with DAPT, a strategy also known as triple antithrombotic therapy, is known to increase the risk of bleeding compared with the use of OAC or DAPT alone. Studies of direct oral anticoagulants are now emerging that show the favorable safety profile of double antithrombotic therapy with OAC and a P2Y12 inhibitor in comparison with triple antithrombotic therapy including the use of vitamin K antagonists. The scope of this review is to provide an update on this topic as well as to discuss future directions in the management of antithrombotic therapy after percutaneous coronary intervention in AF patients requiring chronic OAC. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether the overall effectiveness and safety of direct oral anticoagulants (DOACs) are consistent in patients with nonvalvular atrial fibrillation (AF) and extremely low body weight (<50 kg).Objectives: This study compared DOACs with warfarin in AF patients with low body weight.Methods: Using data from the Korean National Health Insurance Service database from January 2014 to December 2016, AF patients with body weight ≤60 kg and who were treated with oral anticoagulants (n = 14,013 taking DOACs and n = 7,576 taking warfarin) were included and examined for ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding, major bleeding, all-cause death, and composite outcome. The propensity score weighting was used to balance the 2 groups.Results: Baseline characteristics were well balanced between the 2 groups (mean age 73 years, mean CHA2DS2-VASc score 4, and 28% of patients weighed <50 kg). DOACs were associated with lower risks of ischemic stroke (hazard ratio [HR]: 0.591; 95% confidence interval [CI]: 0.510 to 0.686) and major bleeding (HR: 0.705; 95%: CI 0.601 to 0.825), which were caused by a reduction in ICH (HR: 0.554; 95% CI: 0.429 to 0.713) compared with warfarin. DOAC improved the net clinical benefit compared with warfarin (HR for composite outcome: 0.660; 95% CI: 0.606 to 0.717), and this was consistent in patients who weighed <50 kg (HR for composite outcome: 0.665; 95% CI: 0.581 to 0.762).Conclusions: In this real-world Asian AF population with low body weight, DOACs showed better effectiveness and safety than warfarin. These results were consistent in patients with extremely low body weight. Regular dosages of DOACs showed comparable results as reduced dosages of DOACs in both effectiveness and safety. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether edoxaban shows better risk reduction of ischemic stroke, bleeding, and all-cause mortality than warfarin in Asian patients with nonvalvular atrial fibrillation (AF).Objectives: This study compared the effectiveness and safety of edoxaban with those of warfarin in a Korean population with AF.Methods: Using the Korean National Health Insurance Service database, we included new users of edoxaban and warfarin in patients with AF from January 2014 to December 2016 (n = 4,200 on edoxaban, and n = 31,565 on warfarin) and analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH), hospitalization for gastrointestinal (GI) bleeding, hospitalization for major bleeding, and all-cause death. The propensity score matching method was used to balance covariates across edoxaban and warfarin users.Results: We compared a 1:3 propensity score-matched cohort of patients with AF who were new users of edoxaban and warfarin (n = 4,061 and n = 12,183, respectively). Baseline characteristics were balanced between the 2 groups (median age 72 years; median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category (female)] score 3). Edoxaban users had a significantly lower risk of ischemic stroke (hazard ratio [HR]: 0.693; 95% confidence interval [CI]: 0.487 to 0.959), ICH (HR: 0.407; 95% CI: 0.182 to 0.785), hospitalization for GI bleeding (HR: 0.597; 95% CI: 0.363 to 0.930), hospitalization for major bleeding (HR: 0.532; 95% CI: 0.352 to 0.773), and all-cause death (HR: 0.716; 95% CI: 0.549 to 0.918) than warfarin users. All subgroups (age, sex, CHA2DS2-VASc score, renal function, edoxaban dose) showed better clinical outcomes with edoxaban than with warfarin.Conclusions: In this real-world Asian population with AF, edoxaban might be associated with reduced risk of ischemic stroke, major bleeding, and all-cause death compared with warfarin. These benefits were consistent across various high-risk subgroups. [ABSTRACT FROM AUTHOR]

Background: Women with atrial fibrillation are at a higher risk of stroke, despite treatment with warfarin. It is unclear if women treated with direct oral anticoagulants (DOACs) have better clinical outcomes, especially when considering the quality of anticoagulation control of warfarin.Objectives: This study compared the effectiveness and safety outcomes of DOACs versus warfarin in men and women with stratifications for anticoagulation control.Methods: Patients newly diagnosed with atrial fibrillation and prescribed oral anticoagulants during 2010 to 2015 were identified using the Hong Kong clinical database. Propensity score matching was performed in men and women separately. Further analysis was conducted to stratify warfarin users according to their anticoagulation control. Cox regression was used to compare the risk of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding, and all-cause mortality in the specific sex.Results: There were 4,972 men and 4,834 women successfully matched in our cohort. Compared with warfarin, DOAC use was associated with a lower risk of ICH (hazard ratio [HR]: 0.16; 95% confidence interval [CI]: 0.06 to 0.40) and all-cause mortality (HR: 0.55; 95% CI: 0.39 to 0.77) in women but not in men. The treatment by sex interaction was significant for ICH only, and a significantly lower risk of ICH remained in the DOAC group when compared with warfarin users with good anticoagulation control (HR: 0.13; 95% CI: 0.02 to 1.00) among women only. The risks of ischemic stroke or systemic embolism and gastrointestinal bleeding with DOACs versus warfarin were comparable in both sexes.Conclusions: DOACs were associated with a lower risk of ICH and all-cause mortality in women only, where the association of lower ICH risk remained when compared with warfarin users with good anticoagulation control. [ABSTRACT FROM AUTHOR]

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack.Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316.Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0-20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1-5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27-10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29-0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53-0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60-0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07-0·43, p=0·0065; and 0·33, 0·14-0·51, p=0·00059, respectively).Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation.Funding: The Stroke Association and the British Heart Foundation. [ABSTRACT FROM AUTHOR]

Background Both the CHADS2 and CHA2DS2-VASc scores are well-validated in Western populations for predicting risk of stroke among patients with atrial fibrillation (AF). There is some uncertainty as to which risk score is best to guide optimal anticoagulant therapy among Asian populations with AF. Methods A systemic literature search of Cochrane library, Scopus, and PubMed databases was conducted using search terms: atrial fibrillation, CHADS2 and CHA2DS2-VASc. Stroke/thromboembolism (TE) outcome events at low, moderate, and high risk groups were compared in relation to both scores. Statistical analyses were performed using Revman 5.3 software. Results 493 records were retrieved, of which 6 cohort studies focusing on patients from Asian regions were finally appraised and included. Absolute event rates were usually lower when patients were categorized as CHA2DS2-VASc of 0-1, rather than CHADS2 of 0-1, respectively. Meta-analysis revealed that when compared with the CHA2DS2-VASc score, there was a 1.71-fold elevated risk of stroke when patients were stratified as 'low risk' using a CHADS2 score = 0, or a 1.40-fold increase with a CHADS2 score = 1. A 1.19-fold elevated event rate was observed among CHADS2 score ≥ 2 compared to CHA2DS2-VASc, but the total stroke/TE events were numerically higher in patients categorized as CHA2DS2-VASc ≥ 2. Conclusion The CHA2DS2-VASc score is superior to the CHADS2 score in identifying 'low risk' East Asian AF patients. Rather than a categorical approach, Asian guidelines should adopt a 2 step approach, by initially identifying the truly low risk patients, following which effective stroke prevention can be offered to those with ≥ 1 additional stroke risk factors. [ABSTRACT FROM AUTHOR]

Up to 40% of atrial fibrillation (AF) patients are asymptomatic. Despite this, scarce data are available about asymptomatic AF, with regard to its clinical profile and relationship to cerebrovascular and cardiovascular risks. Our objective was to conduct a systematic review and meta-analysis was to study the relationship between age and gender with asymptomatic AF and to establish whether patients with asymptomatic AF have a higher risk of death (all-cause and cardiovascular) and stroke/systemic thromboembolism, when compared to symptomatic AF patients. After a comprehensive search, 6 studies (2 randomized clinical trials and 4 observational studies) were entered in the meta-analysis. Despite significant heterogeneity, our data show that the prevalence of females amongst asymptomatic AF group was significantly less compared to the symptomatic AF group (RR, 0.57; 95% CI: 0.52-0.64). No difference in age between asymptomatic and symptomatic AF patients (P = 0.72) was seen. No differences were found in all-cause death between patients with asymptomatic and symptomatic AF (RR, 1.38; 95% CI: 0.82-2.17), nor in cardiovascular death (RR, 0.85; 95% CI: 0.53-1.36) or stroke/thromboembolism (RR, 1.72 95% CI: 0.59-5.08). Asymptomatic AF is more associated with male sex, irrespective of age. Both general and cardiovascular death risks as well as thromboembolic risk do not seem to be affected by the asymptomatic clinical status. Symptomatic status should not determine our approach to stroke prevention and other cardiovascular prevention therapies, amongst patients with AF. [ABSTRACT FROM AUTHOR]

Introduction Numerous studies have suggested that oral supplementation with resveratrol exerts cardioprotective effects, but evidence of the effects on C-reactive protein (CRP) plasma levels and other cardiovascular (CV) risk factors is inconclusive. Therefore, we performed a meta-analysis to evaluate the efficacy of resveratrol supplementation on plasma CRP concentrations and selected predictors of CV risk. Methods The search included PUBMED, Cochrane Library, Web of Science, Scopus, and EMBASE (up to August 31, 2014) to identify RCTs investigating the effects of resveratrol supplementation on selected CV risk factors. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence intervals (CI) as summary statistics. Results Meta-analysis of data from 10 RCTs (11 treatment arms) did not support a significant effect of resveratrol supplementation in altering plasma CRP concentrations (WMD: - 0.144 mg/L, 95% CI: - 0.968-0.680, p = 0.731). Resveratrol supplementation was not found to alter plasma levels of total cholesterol (WMD: 1.49 mg/dL, 95% CI: - 14.96-17.93, p = 0.859), low density lipoprotein cholesterol (WMD: - 0.31 mg/dL, 95% CI: - 9.57-8.95, p = 0.948), triglycerides (WMD: 2.67 mg/dL, 95% CI: - 28.34-33.67, p = 0.866), and glucose (WMD: 1.28 mg/dL, 95% CI: - 5.28-7.84, p = 0.703). It also slightly reduced high density lipoprotein cholesterol concentrations (WMD: - 4.18 mg/dL, 95% CI: - 6.54 to - 1.82, p = 0.001). Likewise, no significant effect was observed on systolic (WMD: 0.82 mm Hg, 95% CI: - 8.86-10.50, p = 0.868) and diastolic blood pressure (WMD: 1.72 mm Hg, 95% CI: - 6.29-9.73, p = 0.674). Conclusions This meta-analysis of available RCTs does not suggest any benefit of resveratrol supplementation on CV risk factors. Larger, well-designed trials are necessary to confirm these results. [ABSTRACT FROM AUTHOR]

In this large, prospective, real-world population of patients with to VKA-TT group at 3 months follow-up. In a Cox multivariate regression model and propensity-score matched analysis LMWH-TT increased the risk for major BARC bleeding events at 3 and 12 month follow-ups. Conclusions Background Recent reports have provided evidence that bridging therapy with low-molecular-weight heparin (LMWH) may increase bleeding complications in patients with atrial fibrillation (AF) on oral anticoagulation undergoing percutaneous coronary intervention (PCI). We sought to assess mid-term bleeding and thromboembolic events in patients from the AFCAS registry discharged on triple therapy (TT). Methods AFCAS is a multicenter, prospective registry enrolling patients with AF undergoing PCI. The primary endpoints were: 1) bleeding complications as defined by the bleeding academic research criteria (BARC); 2) a composite of cardiac and cerebrovascular events (MACCE) at 3 and 12 month follow-ups. Results Altogether 663 out of 929 consecutive patients were discharged on TT, either on oral vitamin K antagonist (VKA-TT) (n = 498) or bridging LMWH-TT (n = 165). Patients on LMWH-TT had more often diabetes, heart failure, and hypertension compared to those on VKA-TT. The rates of major bleeding events (BARC ⩾ 3) (11.5% vs. 6.0%, p = 0.03) as well as MACCE (11.5% vs. 5.0%, p = 0.006) were higher in the LMWH-TT group compared AF undergoing PCI patients discharged on LMWH-TT had a significantly higher risk for major bleeds in comparison to patients discharged on VKA-TT. LMWH-bridging therapy appeared harmful in this subset of patient on oral anticoagulation. [ABSTRACT FROM AUTHOR]

Introduction Vitamin D (vit D) deficiency may be associated with an increased risk of statin-related symptomatic myalgia in statin-treated patients. The aim of this meta-analysis was to substantiate the role of serum vitamin D levels in statin-associated myalgia. Methods The search included PUBMED, Cochrane Library, Scopus, and EMBASE from January 1, 1987 to April 1, 2014 to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Quantitative data synthesis was performed using a fixed-effect model. Results The electronic search yielded 437 articles; of those 20 were scrutinized as full texts and 13 studies were considered unsuitable. The final analysis included 7 studies with 2420 statin-treated patients divided into subgroups of patients with (n = 666 [27.5%]) or without (n = 1754) myalgia. Plasma vit D concentrations in the symptomatic and asymptomatic subgroups were 28.4 ± 13.80 ng/mL and 34.86 ± 11.63 ng/mL, respectively. The combination of data from individual observational studies showed that vit D plasma concentrations were significantly lower in patients with statin-associated myalgia compared with patients not manifesting this side effect (weighted mean difference - 9.41 ng/mL; 95% confidence interval: - 10.17 to - 8.64; p < 0.00001). Conclusions This meta-analysis provides evidence that low vit D levels are associated with myalgia in patients on statin therapy. Randomized controlled trials are necessary to establish whether vitamin D supplementation reduces the risk for statin-associated myalgia. [ABSTRACT FROM AUTHOR]

Purpose: Atrial fibrillation (AF) is commonly associated with structural heart disease. Although heart failure (HF) has been proposed as a risk factor for stroke, the coexistence of the 2 diseases increases disproportionally the risk of thromboembolic events. Our objective was to conduct a systematic review to assess the effect of HF on the end points of stroke, systemic embolism (SE), or mortality in patients with AF. Methods: A literature search was performed to identify studies that examined stroke/ SE in relation to AF and HF. Overall, 405 articles satisfied the preinclusion criteria. Findings: In studies in which HF was based on a clinical diagnosis, HF independently increased stroke/ SE in 5 of 13 studies, conferring 1.6- to 3.1-fold increase in risk. When HF was defined as impaired left ventricular (LV) function on echocardiography, the additive risk was evident in 4 of 6 studies, with 1.7- to 2.6-fold increase in the risk of stroke/SE. The data about HF with preserved ejection fraction were less robust, although a recent presentation with acute decompensated HF increased the risk of stroke/SE, irrespective of ejection fraction. Implications: LV systolic impairment as identified by echocardiography is an independent risk factor for stroke/SE, although the magnitude by which it increases the risk of stroke cannot be precisely quantified. Whether a clinical diagnosis of HF is a significant risk factor remains inconclusive, although when the diagnosis is certain (recent decompensation requiring hospitalization), t does seem to be a significant risk factor irrespective of LV systolic function. [ABSTRACT FROM AUTHOR]