Prophylaxis Of Atrial Fibrillation Research Articles

Omega-3 Polyunsaturated Fatty Acid Supplementation: Mechanism and Current Evidence in Atrial Fibrillation.

Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with considerable morbidity and mortality. Available pharmacologic antiarrhythmic therapies are often ineffective in preventing the recurrence of AF, possibly because these drugs target a single pathophysiological mechanism. Given their beneficial effects on ventricular arrhythmias, omega-3 polyunsaturated fatty acids (n-3 PUFAs) have recently been investigated as possible candidates in the treatment of supraventricular arrhythmias. In this review, we explore the current understanding of the antiarrhythmic effects attributed to n-3 PUFAs including direct modulation of ionic channels, improvement of membrane fluidity, anti-inflammatory and antifibrotic effects, and modulation of sympatho-vagal balance. We will then focus on the results of epidemiologic studies exploring the associations between nutritional intake of n3 PUFAs and the incidence of AF, and will review the findings of the clinical trials investigating the effects of n-3 PUFAs supplementation in the prophylaxis of AF and in the prevention of its recurrences.

Intravenous Metoprolol versus Biatrial Pacing in the Prevention of Atrial Fibrillation after Coronary Artery Bypass Surgery: A Prospective Randomized Open Trial

Atrial fibrillation (AF) is the most common arrhythmia after coronary artery bypass surgery (CABG). Intravenous metoprolol and biatrial pacing have been reported to be effective in AF prophylaxis after cardiac surgery. The purpose of this trial was to compare the efficacy of intravenous metoprolol versus biatrial pacing combined with oral metoprolol in the prevention of AF after CABG. A single-centre prospective randomized open trial of 165 consecutive patients undergoing their first CABG. Patients were randomized to receive either intravenous metoprolol infusion 1-3 mg per hour or biatrial overdrive pacing and oral metoprolol (50-150 mg) daily for 72 hours after CABG starting immediately after the surgery. AAI pacing with a pacing rate of 10 beats/minute above the baseline heart rate was used. Patients had continuous ECG-monitoring. The primary end point was the first episode of AF. The incidence of postoperative AF in the intravenous metoprolol and biatrial pacing groups did not differ from each other (14% vs. 18% respectively, p=0.66). There was no difference in the time of AF onset between the groups (28.2 ± 16.2 h vs. 30.1 ± 21.2 h respectively, p = 0.8). Intravenous metoprolol infusion had to be temporarily interrupted for one hour in eleven patients because of hypotension or bradycardia. One case of bleeding from the left atria related to the pacemaker electrode wire was found. We found no difference in the incidence of AF between patients treated with intravenous metoprolol or the combination of biatrial pacing and oral metoprolol.

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Introduction: Amiodarone has become the preferred treatment of atrial fibrillation after transthoracic esophagectomy. An 11% rate of occurrence of acute respiratory distress syndrome has been associated with short term use of amiodarone after thoracic surgery. Recent literature has evaluated efficacy but not safety of amiodarone in this population. Hypothesis: Amiodarone administration for atrial fibrillation prophylaxis is associated with an increased rate of acute respiratory distress syndrome after transthoracic esophagectomy. Methods: A retrospective chart review of patients who underwent transthoracic esophagectomy from January 1st, 2007 to June 30th, 2011 at Indiana University Health University Hospital in Indianapolis, Indiana. Patients were categorized based on whether they received amiodarone for atrial fibrillation treatment or prophylaxis after surgery. Patients who received amiodarone prior to surgery, were less than 18 years old, had documented previous episodes of ARDS, underwent esophagectomy due to infection or perforation, or incomplete documentation were excluded. Results: One hundred eighty patient charts met criteria. Ninety one patients received amiodarone after esophagectomy, and eighty nine served as the control group. Incidence of atrial fibrillation was higher in the group receiving amiodarone (14.3% versus 6.7%, p = 0.14); otherwise all other baseline characteristics were not significantly different. Incidence of ARDS was higher in the group receiving amiodarone (14.3% versus 6.7%, p = 0.14); however the difference was not statistically significant. Days on mechanical ventilation, days in the ICU and days in hospital were higher in the amiodarone group. After controlling for atrial fibrillation, only the number of days on mechanical ventilation was significantly different between groups (5.9 versus 4.6 days, p=0.021). Hospital and 28-day mortality were not significantly different. Conclusions: Our study did not find that the incidence of ARDS was significantly affected by the administration of amiodarone. Amiodarone may be associated with increased time on mechanical ventilation.

Sailing between Scylla and Charybdis: oral long-term anticoagulation in dialysis patients

End-stage renal disease (ESRD) patients exhibit an increased risk of bleeding compared with non-chronic kidney disease (CKD) patients due to uraemic platelet dysfunction, altered vessel architecture and other factors. This renders any long-term oral anticoagulation potentially difficult. While there is little doubt that ESRD patients with recurrent thromboembolism or a mechanical cardiac valve should receive vitamin K antagonists (coumarins), the use of coumarins in ESRD patients with atrial fibrillation is a matter of debate. In non-CKD patients, current guidelines strongly recommend the use of oral anticoagulants for stroke prophylaxis in atrial fibrillation if certain risk factors are present (CHA2DS2-VASc score). This recommendation is often extrapolated to patients with advanced CKD or ESRD but data supporting this practice are weak to absent. Besides an increased bleeding risk in ESRD patients, coumarins will also accelerate cardiovascular calcification and are potent risk factors for the development of calcific uraemic arteriolopathy (calciphylaxis). Novel coumarin alternatives such as direct thrombin inhibitors are promising but none is currently approved for use in ESRD patients. Whether interventional treatment strategies such as atrial appendage occlusion are safe and effective options in advanced CKD is also as yet unresolved. This review attempts to balance the potential risks and benefits of coumarin usage in ESRD patients and to give the best possible recommendations for everyday patient care.

Abstract 9103: Rivaroxaban Use is Associated with Reduced Risk of Myocardial Infarction-Insights from a Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials

Introduction: There has been recent evidence to suggest an increased risk of myocardial infarction (MI) with the use of the direct thrombin inhibitor, dabigatran etexilate-approved in the US for prevention of stroke in non-valvular atrial fibrillation. Hypothesis: We systematically evaluated the risk of MI associated with use of the other drug, recently approved for the same indication-rivaroxaban, an oral factor Xa inhibitor. Methods: We searched PubMed, CINAHL, Cochrane CENTRAL, Scopus, and the Web of Science. Randomized controlled trials of rivaroxaban that reported on myocardial infarction as clinical outcomes. The fixed-effects Mantel-Haenszel (M-H) test was used to evaluate the effect of rivaroxaban on MI, in the absence of heterogeneity. Trial sequential analysis (TSA) was performed to ensure validity of our findings. Results: Seven trials were selected (N=45,566), including 1 study of stroke prophylaxis in atrial fibrillation, 2 in acute coronary syndrome, and 4 of short-term prophylaxis of deep venous thrombosis. Control arms included warfarin, enoxaparin, or placebo administration. Rivaroxaban was associated with a significantly lower risk of MI than that seen with agents used in the control group; OR, 0.82; 95% CI, 0.72-0.93; P=0.002). No heterogeneity was noted in the risk (I2=0%; P=0.82), TSA reinforced validity of our findings. Conclusions: Rivaroxaban is associated with a significantly lower risk of MI in a broad spectrum of patients when tested against different controls. We recommend the use of rivaroxaban over dabigatran for nonvalvular AF particularly in patients at high risk of acute coronary events.

A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with significantly increased morbidity and mortality. Cumulative evidence highlights the importance of genetic defects in the pathogenesis of AF. However, AF is of remarkable heterogeneity and the genetic determinants of AF in a vast majority of patients remain illusive. In this study, the coding exons and splice junctions of the GATA5 gene, which encodes a zinc-finger transcription factor essential for normal cardiogenesis, were sequenced in 118 unrelated patients with lone AF. The available relatives of the index patient carrying an identified mutation and 200 unrelated ethnically-matched healthy individuals used as controls were genotyped. The functional effect of the mutant GATA5 was characterized in contrast to its wild-type counterpart using a luciferase reporter assay system. As a result, a novel heterozygous GATA5 mutation, p.W200G, was identified in a family with AF inherited as an autosomal dominant trait. The mutation was absent in 200 control individuals and the altered amino acid was completely conserved evolutionarily across species. Functional analysis showed that the mutation of GATA5 was associated with a significantly decreased transcriptional activity. These findings provide novel insight into the molecular mechanism involved in AF, suggesting potential implications for the early prophylaxis and gene-specific therapy of AF.

Risk stratification for thromboembolism and antithrombotic prophylaxis in atrial fibrillation

Atrial fibrillation (AF) is associated with a significantly high risk of stroke and systemic embolism (4.5%/year). Oral anticoagulant therapy (OAT) with warfarin (INR range 2.0-3.0) significantly reduces thromboembolic risk, whereas aspirin has poor efficacy. In patients with AF, several scoring systems, such as the CHADS2 and CHA2DS2-VASc scores, are currently used to stratify thromboembolic risk. The CHA2DS2-VASc score stratifies patients at intermediate-low thromboembolic risk more accurately than the CHADS2 score. The most recent European and US guidelines on AF have extended the indications for OAT, which is recommended not only for patients at high risk, but also for those at intermediate risk, with CHADS2 score ≥1. However, in clinical practice underuse of OAT, suboptimal quality of anticoagulation, and frequent discontinuations of treatment are observed. Therefore, there is a great expectation for the new oral anticoagulants, in particular the direct thrombin inhibitor dabigatran etexilate and the factor Xa inhibitors rivaroxaban and apixaban, which are at least non-inferior to warfarin and safer, and seem to be a suitable therapeutic alternative to the old warfarin.

Anticoagulant treatment: the end of the old agents?

New oral anticoagulants used as single target inhibitors of coagulation enzymes have been developed and tested in extensive trial programmes. Results of most of these trials showed non-inferior and/or superior efficacy and safety compared to standard treatment with LMWH or VKA. These results led to registration of these agents for the prophylaxis or treatment of thrombosis, as well as stroke prophylaxis in atrial fibrillation. In addition to good efficacy and safety these agents are more convenient in their use and promise advantages in quality of life. Caution is needed, though, since drug-interactions, interferences with coagulation tests and risk of accumulation in case of renal failure should always be taken into consideration when planning a treatment. In the present current-opinion review these advantages and disadvantages are discussed and expressed options are analysed.

New Anticoagulants for Stroke Prophylaxis in Atrial Fibrillation

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is a potent risk factor for stroke and transient ischemic attack. Most patients with AF receive antithrombotic stroke prophylaxis, often in the form of a vitamin K antagonist, typically warfarin. Drug treatment with warfarin is associated with significant management issues, such as an unpredictable dose response necessitating dose adjustments, frequent laboratory monitoring, and multiple interactions with other medications, as well as foods. A new generation of novel anticoagulants has emerged that includes dabigatran etexilate, a direct thrombin inhibitor, and rivaroxaban and apixaban, both highly selective factor Xa inhibitors. These newer agents possess a highly predictable pharmacokinetic-pharmacodynamic relationship, allowing for fixed dosing and no necessity for routine laboratory monitoring; additionally these agents have minimal drug interactions. Dabigatran etexilate and apixaban are both twice-daily medications, whereas rivaroxaban is administered once daily for stroke prophylaxis. The impact of dosing frequency on medication adherence with these agents has not been prospectively evaluated; however, the frequency of dosing intervals has been shown to affect medication adherence, which in turn may influence patient outcomes.

Atrial Fibrillation in Patients Undergoing Surgical Revascularization: An Update on Pharmacologic Prophylaxis

Atrial fibrillation occurs in 20-50% of patients after surgical revascularization (40% have more than 1 episode), with a peak between 2nd and 3rd postoperative days. Postoperative atrial fibrillation (POAF) has been associated with an increase in adverse events, length of hospital stay and, therefore, cost of care, and late mortality. A higher risk profile in patients who develop POAF may contribute to the higher late mortality rate. The pathogenesis of PAOF is multi factorial: transient ischemia during surgical procedure, neurohormonal activation, electrolyte imbalance, fluid overload and finally an exaggerated inflammatory response have been associated with POAF. Advanced age, an history of AF or heart failure and, finally, COPD are clinically independent risk factors related to POAF. The lower incidence of POAF reported after off-pump CABG in comparison to conventional cardiopulmonary by-pass CABG techniques has not been confirmed. The administration of antiarrhythmic drugs (amiodarone, metoprolol, sotalol and recently propafenone and landiolol) before and /or after surgical procedure has been extensively investigated and most of the investigators have demonstrated a favorable effect on POAF incidence. The decreased incidence of POAF and related shorter hospital stay by PUFA administration during hospitalization needs to be confirmed. Preliminary results suggest that pre-treatment with the antianginal drug ranolazine may significantly decrease POAF incidence. Treatments directed to antagonize inflammation are presently under investigation. Recently, a randomized study with naproxen, although effective on POAF, was interrupted due to increased risk of nephrotoxicty. Despite different action mechanisms, both hydrocortisone and statins have been shown to decrease post-operative AF risk. No data at present exist on the effects of association of these drugs. Aim of the present review was to update the current practice and report the recent results of research in the prophylaxis of atrial fibrillation in patients undergoing CABG.

Pre and Post-Operative Treatments for Prevention of Atrial Fibrillation after Cardiac Surgery

Post-operative atrial fibrillation (AF) occurs in up to 40% of cardiac surgery patients and represents the most common post-operative arrhythmic complication. Post-operative AF is associated with impaired cardiac hemodynamics, increased incidence of serious complications (e.g. heart failure, stroke), prolonged hospitalization and increased healthcare costs. Therefore, treatment of post-operative AF would decrease health-care costs during hospitalization and improve the prognosis of patients following cardiovascular surgery. Current consensus guidelines recommend β-blockers, amiodarone and sotalol for post-operative AF prophylaxis. However, new pharmacological agents have been associated with a reduction in post-operative AF frequency, including inhibition of the renin angiotensin aldosterone system (RAAS) using angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), statins, antioxidant agents, magnesium supplementation and antiarrhythmic drugs. The aim of this review is to analyse and determine the efficiency of existing therapies in the reduction of post-operative AF development.

Lysophosphatidic acid as a potential trigger of atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, but its pathogenesis is incompletely understood. Current evidences have highlighted the progression of atrial fibrosis and electrophysiological remodeling in AF development.Lysophosphatidic acid (LPA), the simplest phospholipd, is associated with fibrotic disease and promotes proliferation of a wide variety of fibroblast. It was demonstrated that LPA stimulation in many cell types such as human endothelial cells, human renal fibroblasts, and myoblasts, significantly upregulates connective tissue growth factor (CTGF) expression, which acts as a downstream signaling effector for transforming growth factor-β1 (TGF-β1) to drive fibrosis. We hypothesized that LPA could also evoke growth factor-like responses to atrial fibroblast, and subsequently induce atrial fibrosis to trigger AF. LPA is also verified to involve in numerous electrophysiological activities in non-myocardiocytes. So LPA is a possible cause of AF by initiating fibrosis response and altering electrophysiological properties in atrium. If the hypothesis is confirmed, LPA will act as a new target for AF treatment and administration of LPA receptor blockers may be applied in the prophylaxis of AF.

Exploring barriers to optimal anticoagulation for atrial fibrillation: interviews with clinicians.

BackgroundWarfarin, the most commonly used antithrombotic agent for stroke prophylaxis in atrial fibrillation (AF), requires regular monitoring, frequent dosage adjustments, and dietary restrictions. Clinicians’ perceptions of barriers to optimal AF management are an important factor in treatment. Anticoagulation management for AF is overseen by both cardiology and internal medicine (IM) practices. Thus, gaining the perspective of specialists and generalists is essential in understanding barriers to treatment. We used qualitative research methods to define key issues in the prescription of warfarin therapy for AF by cardiology specialists and IM physicians.Methods and resultsClinicians were interviewed to identify barriers to warfarin treatment in a large Midwestern city. Interviews were conducted until thematic saturation occurred. Content analysis yielded several themes. The most salient theme that emerged from clinician interviews was use of characteristics other than the patient’s CHADS2 score to enact a treatment plan, such as the patient’s social situation and past medication-taking behavior. Other themes included patient knowledge, real-world problems, breakdown in communication, and clinician reluctance.ConclusionWarfarin treatment is associated with many challenges. The barriers identified by clinicians highlight the unmet need associated with stroke prophylaxis in AF and the opportunity to improve anticoagulation treatment in AF. Social and lifestyle factors were important considerations in determining treatment.

Dabigatran in Atrial Fibrillation: New Kid on the Block

In Canada, atrial fibrillation (AF) is the most prevalent cardiac arrhythmia.1 It is associated with an increase in morbidity and mortality, with cardioembolic stroke being one of the most feared complications.2 Anticoagulation is an effective means of reducing the risk of stroke. Currently, warfarin is the preferred agent in patients at high risk of stroke.3,4 However, maintaining warfarin therapy within its narrow therapeutic window is challenging, even for specialized anticoagulation clinics.5 Many factors contribute to the variable dose response of warfarin, such as inter-individual variability, comorbidities and drug and food interactions.5 Dabigatran is a novel therapeutic alternative that provides more predictable anticoagulation with less laboratory monitoring, and it is poised to take over some of warfarin's role in AF stroke prophylaxis. While other novel agents, such as rivaroxaban and apixaban, have proven to be beneficial in stroke prophylaxis in AF, discussion of their roles is beyond the scope of this article.

Cost-effectiveness of pharmacologic and invasive therapies for stroke prophylaxis in atrial fibrillation

Atrial fibrillation is an abnormal heart rhythm characterized by rapid, disorganized activation (fibrillation) of the left and right atria of the heart, and is responsible for 15% of 700,000 strokes in the United States each year. There are multiple pharmacologic and nonpharmacologic therapies used for stroke prevention in atrial fibrillation, including vitamin K antagonists such as warfarin, antiplatelet agents such as aspirin and clopidogrel, and newer agents such as dabigatran, rivaroxaban and apixaban. Nonpharmacologic therapies involve excluding the left atrial appendage from the systemic circulation by surgical ligation or excision, percutaneous ligation, or endovascular implantation of a left atrial occlusion device. Because atrial fibrillation-related stroke is preventable, a comparison of the value of these interventions by cost-effectiveness analysis (CEA) could inform clinical and health policy recommendations. In this article, we review the principles of CEA and identify 11 articles that examine CEA of stroke prophylaxis strategies in atrial fibrillation. Although most studies evaluate aspirin and warfarin across a variety of atrial fibrillation stroke risk profiles, we also review new literature on new pharmacologic therapies such as direct thrombin inhibitors and discuss the potential value of device-based therapies.

Dabigatran Association With Higher Risk of Acute Coronary Events

The original RE-LY (Randomized Evaluation of Long-term Anticoagulant Therapy) trial suggested a small increased risk of myocardial infarction (MI) with the use of dabigatran etexilate vs warfarin in patients with atrial fibrillation. We systematically evaluated the risk of MI or acute coronary syndrome (ACS) with the use of dabigatran. We searched PubMed, Scopus, and the Web of Science for randomized controlled trials of dabigatran that reported on MI or ACS as secondary outcomes. The fixed-effects Mantel-Haenszel (M-H) test was used to evaluate the effect of dabigatran on MI or ACS. We expressed the associations as odds ratios (ORs) and their 95% CIs. Seven trials were selected (N = 30,514), including 2 studies of stroke prophylaxis in atrial fibrillation, 1 in acute venous thromboembolism, 1 in ACS, and 3 of short-term prophylaxis of deep venous thrombosis. Control arms included warfarin, enoxaparin, or placebo administration. Dabigatran was significantly associated with a higher risk of MI or ACS than that seen with agents used in the control group (dabigatran, 237 of 20,000 [1.19%] vs control, 83 of 10,514 [0.79%]; OR(M-H), 1.33; 95% CI, 1.03-1.71; P = .03). The risk of MI or ACS was similar when using revised RE-LY trial results (OR(M-H), 1.27; 95% CI, 1.00-1.61; P = .05) or after exclusion of short-term trials (OR(M-H), 1.33; 95% CI, 1.03-1.72; P = .03). Risks were not heterogeneous for all analyses (I(2) = 0%; P ≥ .30) and were consistent using different methods and measures of association. Dabigatran is associated with an increased risk of MI or ACS in a broad spectrum of patients when tested against different controls. Clinicians should consider the potential of these serious harmful cardiovascular effects with use of dabigatran.

Cost-Effectiveness of Dabigatran for Stroke Prophylaxis in Atrial Fibrillation

Cost-Effectiveness of Dabigatran for Stroke Prophylaxis in Atrial Fibrillation

Atrial fibrillation after coronary artery bypass surgery: Possibilities of prevention

Atrial fibrillation occurs as a frequent complication after cardiac interventions. It can be found in 5% of all surgical patients, and it is far more common in cardiac (10% - 65% of patients) than in non-cardiac procedures. In a number of patients it remains asymptomatic, but may be accompanied by very severe symptoms of hypotension, heart failure, syncope, systemic or pulmonary embolism, perioperative myocardial infarction, cerebrovascular insult and increased operative mortality. Patients whose postoperative course is complicated by atrial fibrillation require longer hospitalization. Possible predisposing factors of this arrhythmia are numerous and are associated with surgery, extensive coronary heart disease and revascularization, and preoperative diseases. According to the recommendations of the European Society of Cardiology orally applied beta-blocker, amiodarone and sotalol can be used for prophylaxis of atrial fibrillation. Following the recommendations, treatment of postoperative atrial fibrillation should include beta-blockers, amiodarone, and in patients with heart failure and left ventricular dysfunction, digoxin. Due to the increased risk of stroke, an anticoagulant protection is necessary. Many studies have been conducted with results supporting the prophylactic use of amiodarone and beta-blockers, while the treatment with new agents such as magnesium, statins, omega-3 fatty acids and inhibitors of the renin-angiotensin-aldosterone system is still being investigated.

POSTER PRESENTATIONS

POSTER PRESENTATIONS

ChemInform Abstract: Oral, Direct Thrombin and Factor Xa Inhibitors: The Replacement for Warfarin, Leeches, and Pig Intestines?

AbstractReview: 74 refs.