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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]

Background: Apixaban (5 mg BID), dabigatran (available as 150 mg and 110 mg BID in Europe), and rivaroxaban (20 mg once daily) are 3 novel oral anticoagulants (NOACs) currently approved for stroke prevention in patients with atrial fibrillation (AF). Objective: The objective of this study was to evaluate the cost-effectiveness of apixaban against other NOACs from the perspective of the United Kingdom National Health Services. Methods: A Markov model was developed to evaluate the pharmacoeconomic impact of apixaban versus other NOACs over a lifetime. Pair-wise indirect treatment comparisons were conducted against other NOACs by using ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy), and ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial results for the following end points: ischemic stroke, hemorrhagic stroke, intracranial hemorrhage, other major bleeds, clinically relevant nonmajor bleeds, myocardial infarction, and treatment discontinuations. Outcomes were life-years, quality-adjusted life years gained, direct health care costs, and incremental cost-effectiveness ratios. Results: Apixaban was projected to increase life expectancy versus other NOACs, including dabigatran (both doses) and rivaroxaban. A small increase in therapeutic management costs was observed with apixaban due to projected gains in life expectancy and lower discontinuation rates anticipated on apixaban versus other NOACs through lifetime. The estimated incremental cost-effectiveness ratio was £9611, £4497, and £5305 per quality-adjusted life-year gained with apixaban compared with dabigatran 150 mg BID, dabigatran 110 mg BID, and rivaroxaban 20 mg once daily, respectively. Sensitivity analyses indicated that results were robust over a wide range of inputs. Conclusions: Although our analysis was limited by the absence of head-to-head trials, based on the indirect comparison data available, our model projects that apixaban may be a cost-effective alternative to dabigatran 150 mg BID, dabigatran 110 mg BID, and rivaroxaban 20 mg once daily for stroke prevention in AF patients from the perspective of the United Kingdom National Health Services. [ABSTRACT FROM AUTHOR]

BACKGROUND AND METHODS: Abnormal circulating endothelial cell (CEC) and circulating progenitor cell (CPC) numbers are present in cancer, but their relationship with angiogenesis, apoptosis, vascular biology, and prognosis is unclear. We prospectively studied 160 patients with breast cancer and 63 age-matched controls free of breast cancer, measuring CECs (CD45-/CD146+/CD34+) and CPCs (CD45-/CD133+/CD34+) by flow cytometry and plasma markers of endothelial damage/dysfunction (von Willebrand factor), apoptosis (Fas/Fas-L) and angiogenesis (vascular endothelial growth factor [VEGF], angiogenin) by ELISA. These were compared with clinicopathophysiologic features and the Nottingham Prognostic Index (NPI). An additional blood sample was taken 6 to 8 weeks after surgery from 15 women to test the effect of tumor removal. RESULTS: CECs were significantly higher in the NPI poor prognostic group compared with moderate and good prognostic groups, and the cancer-free controls, whereas CPCs were lower in the poor prognosis group (both P < .05). Levels of von Willebrand factor, VEGF, angiogenin, and Fas-L (but not soluble Fas) were abnormal in breast cancer compared with controls (P < .05), with no relationship to prognosis groups. VEGF (P = .04) and angiogenin (P = .001) were markedly different after surgery. In multivariate analysis, vascular invasion (P < .05) and tumor size (P < .001) were independently associated with CECs. CPCs did not significantly associate with NPI in a linear regression model; age (P < .05) was a negative predictor, whereas Her-2 status (P < .05) positively predicted CPCs. After adjustment, no variable independently predicted CPC levels. CONCLUSIONS: CECs and CPCs demonstrate a strong relationship with NPI groups, but only CECs positively predict higher NPI scores and correlate with tumor invasiveness and size, possibly reflecting total tumor vascular volume. [ABSTRACT FROM AUTHOR]

In a multiethnic cohort of 388 patients admitted with symptomatic peripheral artery disease, atrial fibrillation was associated with emergency admission and increased mortality. Despite a greater prevalence of hypertension and diabetes in Afro-Caribbeans and diabetes in Indo-Asians, no significant differences were found in atrial fibrillation prevalence or mortality among different ethnic groups. Patients with symptomatic peripheral artery disease and atrial fibrillation should be regarded as “high risk” and managed with optimal medical therapy, including appropriate thromboprophylaxis and close follow-up. [Copyright &y& Elsevier]

We report a double-blind, multicenter, multinational, placebo-controlled, and well-controlled trial to prove that the sustained-release (SR) formulation of propafenone is superior to placebo in preventing symptoms of paroxysmal atrial fibrillation (AF). A total of 594 patients were enrolled in the qualifying period of the study and 293 patients were randomized at 53 centers. There were significant increases in the arrhythmia-free periods from day 5 of randomization to the first recurrence of symptomatic atrial arrhythmia in the propafenone SR 325 mg twice daily (p = 0.004) and propafenone SR 425 mg twice daily (p = 0.003) treatment groups compared with placebo. The median arrhythmia-free time was 9 days in the placebo group, 35 days in the propafenone SR 325 mg twice daily group, and 44 days in the propafenone SR 425 mg twice daily group. There was a significant reduction in average heart rate during the first recurrence of symptomatic arrhythmia after day 5 in the low-dose propafenone group compared with placebo. The median treatment failure time from day 5 (arrhythmia recurrence, adverse events, and withdrawals) was prolonged from 8 days in the placebo group to 19 days in the propafenone SR 325 mg twice daily group (p = 0.002) and to 24 days in the propafenone SR 425 mg twice daily group (p = 0.006). The percentage of patients with ≥1 serious adverse event was similar in the propafenone SR treatment groups (propafenone SR 325 mg twice daily, 10.0%; propafenone SR 425 mg twice daily, 11.2%) but lower in the placebo group (1.1%). In conclusion, the SR formulation of propafenone is superior to placebo, well-tolerated, and prevents symptoms of paroxysmal AF. [Copyright &y& Elsevier]

• 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]

Describes the pathophysiology of the hypercoagulable state of cancer. Causes of prothrombotic state of malignancy; Prothrombotic factors in cancer; Information on tumor cells.

• 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]

The article focuses on the co existence of Atrial Fibrillation and Heart Failure in a patient because of several risk factors including hypertension, increasing age and valvular heart disease. Topics discussed include use of a 2-dimensional echocardiogram, role of heart failure in impacting anticoagulation of blood in patients and heart failure can prove to be fatal in therapeutic treatment.

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]

The hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, and drugs/alcohol (HAS-BLED); anticoagulation and risk factors in atrial fibrillation (ATRIA); modified Outpatient Bleeding Risk Index (mOBRI); and reduction of atherothrombosis for continued health (REACH) schemes are validated bleeding risk-prediction tools, but their predictive performance in patients with AF receiving multiple antithrombotic drugs after percutaneous coronary intervention (PCI) is unknown. We sought to compare the predictive performance of bleeding risk-estimation tools in a cohort of patients with atrial fibrillation (AF) undergoing PCI. Management of patients with AF undergoing coronary artery stenting is a multicenter European prospective registry enrolling patients with AF undergoing PCI. We calculated HAS-BLED, ATRIA, mOBRI, and REACH bleeding risk-prediction scores and assessed the rate of bleeding complications as defined by Bleeding Academic Research Consortium at 12 months follow-up in 929 consecutive patients undergoing PCI. Increasing age, femoral access site, and previous peptic ulcer were independent determinants of bleeding. Low bleeding risk scores as determined by HAS-BLED 0 to 2, ATRIA 0 to 3, mOBRI 0, and REACH 0 to 10 were detected in 23.7%, 73.0%, 7.8%, and 5.7% of patients of the cohort, respectively. No significant differences were detected in the rates of any bleeding or major bleeding events for low versus intermediate/high scores with each risk-prediction tool. In conclusion, the performance of ATRIA, HAS-BLED, mOBRI, and REACH scores in predicting bleeding complications in this high-risk patient subset was useless. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is often regarded as a risk factor for bleeding complications in patients undergoing percutaneous coronary intervention (PCI). The risk of mild to moderate baseline and acquired thrombocytopenia on bleeding and thrombotic or thromboembolic complications in patients with atrial fibrillation on oral anticoagulation therapy undergoing PCI, however, remains largely unknown. Management of Patients With Atrial Fibrillation undergoing Coronary Artery Stenting is a multicenter European prospective registry enrolling patients with atrial fibrillation undergoing PCI. We assessed the rate of bleeding complications as defined by Bleeding Academic Research Consortium and a composite of major adverse cardiac and cerebrovascular events (MACCE) including all-cause mortality, myocardial infarction, transient ischemic attack or stroke, stent thrombosis, systemic arterial embolism, or revascularization; and a composite of any harmful event (Bleeding Academic Research Consortium and MACCE) at 12-month follow-up in 861 consecutive patients undergoing PCI. Patients were divided into those with mild to moderate baseline thrombocytopenia (platelet count <150 × 109/L; n = 99) and control group (platelet count >150 × 109/L; n = 762). At hospital discharge, thrombocytopenia had no effect on prescribed antithrombotic treatment, and triple therapy (vitamin K antagonist + aspirin + clopidogrel) was the most common combination in both patient groups (69% vs 73%, p = 0.40). No differences in all-cause mortality (12% vs 11%, p = 0.79), MACCE (23% vs 22%, p = 0.87), or bleeding complications (23% vs 19%, p = 0.26) were detected. Acquired in-hospital thrombocytopenia occurred in 9.7% of patients, and it was associated with similar risk of adverse outcomes compared with control group. In conclusion, mild to moderate baseline thrombocytopenia does not seem to have a clinically significant effect on bleeding or thrombotic or thromboembolic complications after PCI in these frail patients receiving multiple antithrombotic drugs. [ABSTRACT FROM AUTHOR]

Renal dysfunction is highly prevalent among patients with atrial fibrillation (AF) and confers an increased risk of thrombotic and bleeding complications. We evaluated the effect of renal function on prognosis in anticoagulated patients with AF and assessed the changes in renal function during a long-term follow-up period. We recruited 978 consecutive stable anti-coagulated patients with AF from our outpatient anticoagulation clinic (international normalized ratio 2.0 to 3.0 within the previous 6 months). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation at inclusion and 2 years of follow-up. Adverse events were recorded during follow-up (throm-botic/vascular events, major bleeding episodes, and mortality). Longitudinal changes in renal function were analyzed in 886 patients (90.6%). At baseline, the median eGFR using the Modification of Diet in Renal Disease equation was 70.24 ml/min/1.73 m2 (interquartile range 46.79 to 72.52). During follow-up, a low eGFR was associated with thrombotic/vascular events, with every 30 ml/min/1.73 m2 eGFR decrease (hazard ratio 1.42, 95% confidence interval [CI] 1.11 to 1.83, p = 0.006), bleeding (hazard ratio 1.44, 95% CI 1.08 to 1.94, p = 0.015), and mortality (hazard ratio 1.47, 95% CI 1.13 to 1.91, p = 0.004). After excluding patients with a baseline eGFR <30 ml/min/1.73 m2, the mean eGFR in our cohort decreased >10 ml/min/1.73 m2 in 181 patients (21%) during the follow-up period. The variables asso-ciated with severe renal impairment during follow-up were heart failure (odds ratio 3.58,95% CI 1.36 to 9.42, p = 0.010), basal eGFR (odds ratio 6.34,95% CI 2.44 to 16.50, p <0.001), and CHADS2 (Congestive heart failure, Hypertension, Age >75 years, Diabetes mellitus, and previous Stroke or transient ischemic attack [doubled]) score (odds ratio 1.63, 95% CI 1.19 to 2.23, p = 0.003). In conclusion, the presence of impaired renal function was closely related to thrombotic/vascular events, bleeding, and mortality in anticoagulated patients with AF. During follow-up, 1/5 of the patients had significant impairment in renal function. Impor-tantly, normal or mild renal dysfunction at baseline did not exclude the subsequent devel-opment of severe renal dysfunction during the follow-up period. [ABSTRACT FROM AUTHOR]

Excessive atrial fibrosis is involved in the pathogenesis of atrial fibrillation (AF), but little is known of left ventricular (LV) fibrotic status in patients with AF. In the present study, we investigated the presence of abnormal LV fibrosis in AF, its effect on cardiac function, a possible association with arterial stiffness (i.e., systemic cardiovascular fibrosis), and the parameters of endothelial activation, dysfunction, and damage. We also studied whether LV fibrosis could be linked to the future risk of AF onset. In a cross-sectional study, the severity of LV fibrosis was assessed by echocardiographic acoustic densitometry in patients with permanent AF (n [ 49), patients with paroxysmal AF (n [ 44), AF-free "disease controls" (n [ 42) and "healthy controls" (n [ 48). Arterial stiffness (pulse wave velocity), plasma markers of endothelial activation (E-selectin), endothelial damage/dysfunction (von Willebrand factors), and microvascular endothelial function (laser Doppler flowmetry) were quantified. In a longitudinal study, 93 patients with pacemakers (22 with AF) were followed up for ‡1 year to assess the predictive value of LV fibrosis for the development of new-onset AF. More severe LV fibrosis was present in both paroxysmal and permanent AF than in the AF-free controls (p <0.001), with more LV fibrosis in permanent than in paroxysmal AF (p [ 0.002). The severity of LV fibrosis in AF wais independently associated with diastolic dysfunction (p [ 0.03), but not with LV contractility, arterial stiffness, or endothelial damage/dysfunction. In conclusion, LV fibrosis might contribute to LV diastolic dysfunction and the high prevalence of heart failure with preserved ejection fraction in subjects with AF. [ABSTRACT FROM AUTHOR]

Warfarin decreases risk of stroke for patients with atrial fibrillation (AF) dependent on percent time in the therapeutic range (TTR) with an international normalized ratio (INR) of 2 to 3. We hypothesized that gender differences in ischemic stroke risk are related to TTR. From the AFFIRM database of 4,060 patients with AF, we determined the incidence of ischemic stroke by gender. We evaluated the INR at time of ischemic stroke and calculated TTR. We determined the relation between gender and ischemic stroke by TTR. Women had CHADS2 Scores (3.7 ± 1.3 vs 2.5 ± 1.3, p <0.0001) and more ischemic strokes than men (5% vs 3%, odds ratio 1.6, 95% confidence interval 1.19 to 2.26, p = 0.002). Mean INR near time of ischemic stroke was 2 for women and men; median values were subtherapeutic (1.7 and 1.8, respectively). Women spent more time outside the therapeutic range (40 ± 0.7% vs 37 ± 0.5%, p = 0.0001), with more time below the therapeutic range (29 ± 0.7% vs 26 ± 0.5%, p = 0.0002). A higher TTR protected against ischemic stroke for women but not for men. Women who had a comparably high TTR (=66%) still had more ischemic strokes (p = 0.009). A fitted Cox proportional hazard regression model showed that gender, TTR <46% versus >80%, age, and previous stroke were significantly related to stroke incidence. In conclusion, women in AFFIRM were at greater risk of ischemic stroke than men, in part related to differences in TTR. Women with AF may benefit from more aggressive or novel anticoagulation to decrease their risk of stroke. [ABSTRACT FROM AUTHOR]