Qinmei Xiong

Asymptomatic versus symptomatic atrial fibrillation: A systematic review of age/gender differences and cardiovascular outcomes

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.

Non-vitamin K antagonist oral anticoagulants (NOACs) in patients with concomitant atrial fibrillation and heart failure: a systemic review and meta-analysis of randomized trials

No pooled analysis has been undertaken to assess the efficacy and safety of the non‐vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in the subgroup of patients with atrial fibrillation (AF) and heart failure (HF), including edoxaban data from recent randomized controlled trials (RCTs).

Suboptimal oral anticoagulant treatment among Chinese non-valvular atrial fibrillation patients: the Nanchang Atrial Fibrillation Project

When used as thromboprophylaxis in patients with atrial fibrillation (AF), oral anticoagulant (OAC) therapy is effective for preventing stroke and thromboembolism (by 64%) and all-cause mortality (by 26%) [1]. Thus, current guidelines recommend OAC in AF patients with ≥ 1 additional stroke risk factors according to the CHA2DS2-VASc score. Nevertheless, underuse of OAC is common, but there are limited data on clinical features associated with the non-use of OAC in Asian countries. This is despite the significant burden of AF in Asian countries, which is increasing and numerically larger than that in Western countries [2]. Due to limitations in access to OAC in the nationwide healthcare system in China, we focused on a hospitalized cohort from Nanchang city to provide insights into OAC use (essentially warfarin, given the limited use of novel anticoagulants in China) among patients with non-valvular AF, and to explore the association between clinical characteristics associated with OAC use. We studied consecutive non-valvular AF patients admitted to the cardiovascular department from May 2011 to December 2013 in the Second Affiliated Hospital of Nanchang University. This is a 2340-bed teaching hospital with 48 attending cardiologists working in the cardiovascular department (15 with an arrhythmia interest). Atrial fibrillation was diagnosed by the attending physician based on an electrocardiogram or Holter monitor. Patients with valvular heart disease requiring surgical management were excluded. Medical records were reviewed to extract data including demographic characteristics, OAC therapy after admission and co-morbidities. The CHA2DS2-VASc score was calculated to assess the risk of stroke and thromboembolism. Continuous variables, presented as mean ± standard deviation (SD) or medians and interquartile ranges (IQR), were compared using the T-test or Mann-Whitney U-test, respectively. Comparisons of categorical variables, presented as n (%), were undertaken using the χ2 test. Univariate and multivariate logistic regression analyses were performed to evaluate associations between clinical factors and OAC use. All analyses were performed using SPSS 21.0 (Inc., Chicago, IL) and a two-sided p < 0.05 was considered statistically significant. The study cohort consisted of 1453 patients (mean age 69.1 ±11.2 years; 44.7% female), among whom 647 (44.5%) patients received OAC treatment (i.e., warfarin) after admission. Atrial fibrillation patients taking warfarin were younger than those not taking warfarin (p < 0.001) (Table I). The proportions of patients receiving warfarin significantly decreased with increasing age, with only 36.7% of warfarin users among patients aged ≥ 75 years. There were no significant differences in subtype of AF or CHA2DS2-VASc score between warfarin users and non-users. Among high-risk patients with a CHA2DS2-VASc score ≥ 2 in males or ≥ 3 in females, only 45.1% of patients received warfarin therapy after admission. Table I Patient characteristics categorized by warfarin use Univariate analysis shows that warfarin use was negatively associated with age ≥ 75 years and concomitant coronary artery disease, but positively related to prior stroke/transient ischemic attack (TIA)/thromboembolism (TE), history of hypertension and diabetes mellitus (Table II). On multivariate analysis, predictors of warfarin use during hospital admission were hypertension (odds ratio (OR) 1.43; 95% confidence interval (CI) 1.14–1.79, p = 0.002) and prior stroke/TIA/TE (OR = 1.59; 95% CI: 1.18–2.16, p = 0.003), whilst age ≥ 75 years (OR = 0.54; 95% CI: 0.43–0.69, p < 0.001) and coronary artery disease (OR = 0.62; 95% CI: 0.48–0.80, p < 0.001) were independently associated with less frequent warfarin use (Table II). Table II Clinical predictors associated with warfarin use The use of warfarin was very low in previous community-based Chinese cohort studies [3, 4]. With the awareness of the importance of OAC therapy in AF management, warfarin prescription has increased recently, but it still remains under-prescribed. The present study demonstrates suboptimal warfarin use in hospitalized patients with non-valvular AF. Importantly, age ≥ 75 years was a predictor of non-use of warfarin in our Chinese cohort, which is consistent with prior data from China [5]. Elderly patients with non-valvular AF have a relatively high risk of both ischemic stroke and major bleeding [6], but the benefits of warfarin over aspirin (or non-treatment) have been evident from observational cohorts and trials [7]. In the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) trial, for example, warfarin was superior to aspirin for the prevention of thromboembolism among elderly AF patients aged ≥ 75 years, with no significant difference in major bleeding or intracranial haemorrhage [8]. Additionally, we found that concomitant coronary artery disease had a negative impact on warfarin use. This is perhaps due to AF patients with coronary artery disease being co-treated with antiplatelet agents. This combination therapy of warfarin and antiplatelet would increase bleeding risks. Also, the older CHADS2 scoring system is widely used in China to guide decisions on thromboprophylaxis, in which vascular disease was not considered as a risk factor for stroke among AF patients. The reason for the use of warfarin in many low-risk patients could be due to the catheter radiofrequency ablation. Two positive predictors of warfarin use in this cohort were hypertension and prior stroke/TIA/TE, which are both risk factors for ischemic stroke among patients with non-valvular AF. Hypertension is clearly a strong stroke risk factor among Chinese cohorts [9], as is prior stroke/TIA/TE. In conclusion, warfarin use is suboptimal in Chinese hospitalized AF patients, even among high-risk individuals (i.e., CHA2DS2-VASc score ≥ 2). Age ≥ 75 years and presence of coronary artery disease are negative predictors of warfarin use. Interventions to improve arrhythmia awareness and effective stroke prevention with OAC in China are urgently needed.

Sex differences in clinical characteristics and inpatient outcomes among 2442 hospitalized Chinese patients with nonvalvular atrial fibrillation: The Nanchang Atrial Fibrillation Project

BACKGROUND Limited data exists on the impact of sex on clinical characteristics and outcomes among nonvalvular AF patients from China. We investigated the impact of gender on risk factors and inpatient mortality in a hospitalized nonvalvular AF cohort in Nanchang, China. METHODS We studied consecutive patients hospitalized with nonvalvular AF between May 2011 and December 2013. Predictors of inpatient mortality were evaluated using multivariate regression analyses. RESULTS We studied 2442 patients (43.7% female; mean age 71.8), with a median hospital stay of 10 days (IQR: 7-14). Inpatient mortality was 2.2%. Mean age, CHADS2 and CHA2DS2-VASc scores were higher in females vs. males (all p<0.0001). Oral anticoagulation use during hospitalization was 33.3% without sex differences, and length of stay and inpatient outcomes were comparable between sexes. On multivariate analyses, the significant risk factors of inpatient death in females were previous ischemic stroke/transient ischemic attack (TIA)/thromboembolism (TE) (Odds Ratio (OR): 2.27; 95% Confidence Intervals (CI): 1.43-3.61), peripheral artery disease (OR: 5.75, 95% CI: 1.49-22.16) and chronic renal disease (OR: 5.68, 95% CI: 1.46-22.13). Among males, only age (OR: 1.06, 95% CI: 1.02-1.11) and previous ischemic stroke/TIA/TE (OR: 1.81, 95% CI: 1.25-2.63) were independent predictors of inpatient mortality. CONCLUSION Sex related differences in clinical characteristics and stroke risk profile were evident in Chinese nonvalvular AF patients, but no sex disparity was evident in the low antithrombotic therapy use or inpatient mortality. Previous ischemic stroke/TIA/TE was an important predictor of inpatient mortality in both female and male patients.

Relationship between renal function and circulating microparticles, soluble P-selectin and E-selectin levels in atrial fibrillation

Atrial fibrillation (AF) and chronic kidney disease are closely related, and any associated risk of stroke and thromboembolism due to AF is increased by concurrent renal dysfunction. The mechanism(s) for this include abnormalities in platelets and endothelial cells. We hypothesized relationships between levels of circulating platelet microparticles (PMPs, defined by CD42b), soluble P selectin (both reflecting platelet activation), soluble E-selectin (reflecting endothelial activation) and endothelial/platelet microparticles (EPMPs, defined by CD31) with progressive renal dysfunction. Blood samples were obtained from 160 anticoagulated AF patients. Microparticles were measured by flow cytometry, soluble E and P selectin levels by ELISA. Renal function was determined by estimated glomerular filtration rate (eGFR). EPMP levels demonstrated a linear increased trend across quartiles of eGFR (p = 0.034) and CKD stage (p < 0.001), and correlated with eGFR and serum creatinine (p < 0.01). PMPs, P-selectin and E-selectin levels were not significantly different across groupings of renal dysfunction, and no significant correlations with eGFR were evident (p = 0.186, p = 0.561, p = 0.746 respectively). Stepwise multivariable regression analysis demonstrated that worsening renal function was an independent predictor of EPMP levels (p < 0.001). In well-anticoagulated AF patients, there is potential relationship between endothelial function (as judged by elevated EPMP levels, with no change in PMPs) and renal function. Other markers of prothombotic state or cellular activation (PMP, P-selectin and E-selectin levels) were not significantly different across the various degree of renal dysfunction. Renal function must be addressed when measuring EPMP levels.

GW26-e2302 Non-vitamin K Antagonist Oral Anticoagulants (NOACs) in Patients with Atrial Fibrillation and Heart Failure: A Systemic Review and Meta-analysis of randomized trials

RESULTS The levels of serum CRP was 13.05 3.68mg/L and blood Hcy was 21.17 8.63 mmol/L in patients with coronary heart disease were higher than those in the control group(5.02 1.60 g/L, 8.15 2.03 mmol/L), the differences were statistically significant(P <0.05). The levels of serum CRP and blood Hcy in the acute myocardial infarction subgroup of coronary heart disease patients(19.62 3.03 mg/L, 32.10 7.02 mmol/L) were higher than those in the unstable angina pectoris subgroup(12.98 6.11 mg/L, 20.82 6.04 mmol/L)(P <0.05); while, the levels of serum CRP and blood Hcy in the unstable pectoris angina subgroup were higher than those in the stable angina pectoris subgroup[(7.65 4.81) mg/L,(14.01 4.30) mmol/L], the differences were statistically significant (P <0.05).

Apixaban versus edoxaban for stroke prevention in nonvalvular atrial fibrillation

Oral anticoagulation therapy is the mainstay of stroke prevention in nonvalvular atrial fibrillation patients. Vitamin K antagonists (such as warfarin) have been effective conventional oral anticoagulants for several decades. However, due to their limitations in clinical use, several nonvitamin K antagonist oral anticoagulants (NOACs, including dabigatran, rivaroxaban, apixaban and edoxaban) have been developed. Nonetheless, no head to head trials have been performed to directly compare these NOACs in patient cohorts. In this review article, two direct factor Xa inhibitors, apixaban and edoxaban, are briefly described with focus on their pharmacokinetic and pharmacodynamic profiles, plus drug interactions. Moreover, both efficacy and safety will be discussed based on the available data from the large Phase III clinical trials and indirect comparison studies.

Pharmacodynamic profile and drug interactions with non-vitamin K antagonist oral anticoagulants: implications for patients with atrial fibrillation

Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to prevent ischemic stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. Owing to their predictable pharmacological profiles, they can be given in fixed doses without the need for routine coagulation monitoring. However, their distinctive pharmacological properties also raise issues about potential drug interactions. Areas covered: A literature search was conducted to extract published studies on the pharmacodynamics and drug interactions involving NOACs. Available data from US FDA and European Medicine Agency were also included. As these agents are substrates of permeability glycoprotein (P-gp) efflux transporter and/or CYP3A4 enzymes, articles focusing on the co-administration of NOACs and drugs affecting these pathways are discussed. Concomitant use of NOACs with antiplatelet agents may potentially increase bleeding risk. Expert opinion: Measurement of anticoagulant effects is desired to evaluate the risk of thromboembolism or bleeding for patients with NOACs. Prescribers should be vigilant against combination prescription of NOACs with strong inhibitors (such as ketoconazole) or inducers of P-gp and/or CYP3A4 (such as rifampicin). Potential benefit of concurrent use of these agents with antiplatelet drugs should be cautiously balanced against latent risk in specific clinical situations.