Yee Cheng Lau

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).

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants vs. Warfarin in Japanese Patients With Atrial Fibrillation

BACKGROUND Non-vitamin K antagonist oral anticoagulants (NOAC) have been developed as alternatives to warfarin. Until recently, the latter was the standard oral anticoagulant for patients with non-valvular atrial fibrillation (NVAF). The efficacy and safety of NOAC in Japanese patients with NVAF has been investigated in small trials or subgroups from global randomized control trials (RCT). METHODS AND RESULTS We conducted a systematic review and meta-analysis of RCT, to compare the efficacy and safety of NOAC to those of warfarin in Japanese patients with NVAF. Published research was systematically searched for RCT that compared NOAC to warfarin in Japanese patients with NVAF. Random-effects models were used to pool efficacy and safety data across RCT. Three studies, involving 1,940 patients, were identified. Patients randomized to NOAC had a decreased risk for stroke and systemic thromboembolism (relative risk [RR], 0.45; 95% CI: 0.24-0.85), with a non-significant trend for lower major bleeding (RR, 0.66; 95% CI: 0.29-1.47), intracranial bleeding (RR, 0.46; 95% CI: 0.18-1.16) and gastrointestinal bleeding (RR, 0.52; 95% CI: 0.25-1.08). CONCLUSIONS NOAC are more efficacious than warfarin for the prevention of stroke and systemic embolism in Japanese patients with NVAF. The present findings offer clinicians a more comprehensive picture of NOAC as a therapeutic option to reduce the risk of stroke in Japanese NVAF patients.

Updated NICE guideline: management of atrial fibrillation (2014)

There is significant progress made in the field of atrial fibrillation, especially regarding stroke stratification, novel pharmacological agents and interventions for improving symptom control. The Updated NICE Guideline for management of 2014 reflects that and provided an up-to-date appraisal regarding atrial fibrillation treatment, management with consideration to overall healthcare cost economics. It emphasizes the need for individualized, patient-centered package of care, and an robust stroke and bleeding risk before decision regarding choice of oral anticoagulation to be made.

Atrial Fibrillation in Cryptogenic Stroke Look Harder, Look Longer, But Just Keep Looking

Despite atrial fibrillation (AF) being the most common cardiac arrhythmia, its asymptomatic (and sometimes, paroxysmal) nature makes subsequent detection and diagnosis challenging. Ischemic stroke as a result of AF is usually more severe and results in greater functional loss, and patients with undetected AF will undoubtedly by at greater risk of recurrent stroke. The failure to diagnose AF after stroke also relegates this particularly vulnerable group to using antiplatelet agents, which are known to be only minimally effective in established AF, while placing them at similar risk of hemorrhagic complications as with oral anticoagulation therapy. Current guidelines (both European and American) recommend the use of short-term (usually 24 hours) cardiac monitoring among stroke and patients with transient ischemic attack for whom occult AF or paroxysmal AF is suspected, and no other causes for stroke are found.1,2 However, even in selected high-risk patient group (such as the elderly, cryptogenic stroke patients, etc), the use of 24-hour ECGs only improve new AF detection rates to just >10%,3 whereas extended monitoring (>24 hours) with external loop recorder or implantable device can further increase detection rates to >14%. This would suggest that longer cardiac monitoring among patients with cryptogenic stroke is indicated and would have important therapeutic and clinical implications. Therefore, current guidelines and strategies for AF detection may need to be reviewed. Until recently, the evidence-base for protracted cardiac monitoring among such patients relied on relatively …

Development and validation of a new assay for assessing clot integrity

INTRODUCTION Research and routine laboratory assessment of clot integrity can be time consuming, expensive, and cannot be batched as it is generally performed in real time. To address these issues, we developed and validated a micro-titre based assay to quantify thrombogenesis and fibrinolysis, the purpose being to assess patients at risk of cardiovascular events by virtue of hypercoagulability. In further validation, thrombogenesis results were compared to similar indices from the thrombelastograph (TEG). METHODS Our assay determines three indices of thrombogenesis (lag time to the start of thrombus formation (LT), rate of clot formation (RCF), and maximum clot density (MCD)) and two of fibrinolysis (rate of clot dissolution (RCD) and time for 50% of the clot to lyse (T50)). Plasma was tested fresh and again after being frozen at -70°C. Some samples were tested immediately, others after being left at room temperature for up to 24h. RESULTS The intra-assay coefficients of variation (CVs) of the three thrombogenesis measures (LT, RCF, MCD) and two fibrinolysis measures (RCD, T50) varied between 2.7 and 12.0% in fresh plasma and between 1.3% and 10.8% in frozen plasma respectively. Similarly, the inter-assay coefficients of variation of the thrombogenesis and fibrinolysis measures were 4.9-10.8% in fresh plasma and 2.2-6.5% in frozen plasma respectively. TEG assays intra- and inter assay CVs were around 25%. There were no significant differences in all plate assay indices up to 6h at room temperature. Certain plate assay thrombogenesis data were comparable to TEG indices after analysis by Pearsons correlation. The reagent processing cost per sample is £15 for TEG and £2 for the plate assays. CONCLUSION Our micro-titre based assay assessing plasma thrombogenesis and fibrinolysis has good intra- and inter-assay CVs, can assess plasma up to 6h after venepuncture, is more efficient (in terms of throughput) and is more economical than that of the TEG.

Altered fibrin clot structure in patients with atrial fibrillation and worsening renal function

Altered fibrin clot structure in patients with atrial fibrillation and worsening renal function -

Vernakalant hydrochloride to treat atrial fibrillation

Introduction: Intravenous vernakalant (Brinavess) has been developed and approved in Europe as a safe and efficacious drug to rapidly convert recent onset atrial fibrillation to sinus rhythm in patients with no minimal or structural heart disease. Areas covered: The pharmacology of vernakalant and the pivotal Phase II and III clinical trials undertaken during its development are discussed with regard to safety and efficacy. An extensive PubMed search was used to identify suitable papers. Expert opinion: As yet, there is no evidence of benefit over and above intravenous flecainide or propafenone for patients in whom vernakalant has a class 1a recommendation. As such, it is likely to be most useful in centres where only amiodarone is available.

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.

Effect of renal function on whole blood and fibrin clot formation in atrial fibrillation patients on warfarin.

Abstract Objective: Atrial fibrillation (AF) brings a risk of thrombosis, requiring oral coagulation, and is associated with renal impairment. The two processes may be linked, as altered fibrin clot structure is present in end-stage renal failure. We hypothesised that progressively deteriorating renal function is linked to altered whole blood and fibrin clot properties and fibrinolysis. Methods: Thrombogenesis and fibrinolysis in 200 warfarinised AF patients was assessed by thromboelastography (TEG), a micro-plate assay (MPA) and the international normalized ratio (INR). Renal function was determined by creatinine clearance and two versions of the estimated glomerular filtration rate (eGFR). Results: Two TEG indices independently reflecting thrombogenesis were linked to creatinine clearance (p < 0.01), whilst a third, reflecting clot strength, was linked to the eGFR (p < 0.001). MPA indices of thrombogenesis and clot density (p < 0.001), and an index of fibrinolysis (p < 0.001) were linked to the eGFR. The time for 50% of the fibrin clot to lyse was linked to creatinine clearance (p = 0.001). The INR was unrelated to any renal function index, and the CHA2DS2VASc score was unrelated to any index. Conclusion: In warfarinised AF patients, renal function is linked to whole blood clot and fibrin clot formation, structure and dissolution, but has no effect on the INR. Key messages Despite oral anticoagulation, patients with atrial fibrillation (AF) still suffer from stroke and venous thromboembolism. The effect of renal function in warfarinised patients with AF is unknown and may account for excess thrombosis and/or haemorrhage. Using two different laboratory methods, our data point to an effect of renal function on clot structure and function that is independent of an effect of warfarin.