Anticoagulation In Nonvalvular Atrial Fibrillation Research Articles

Anticoagulation for Nonvalvular Atrial Fibrillation in an Asian Population

The direct anticoagulants dabigatran and rivaroxaban are at least as effective as warfarin, with fewer major bleeding events. However, whether this is

Multidisciplinary meeting about the use of direct oral anticoagulants in nonvalvular atrial fibrillation

Knowing the real impact of atrial fibrillation in the stroke, the Sociedad Mexicana of Electrofisiología y Estimulación Cardiaca (SOMEEC) had the initiative to develop a multidisciplinary meeting of experts the with the purpose to update the available scientific evidence from clinical practice guidelines, meta-analyses, controlled clinical trials, and complementing with the experience and views of a group of experts. To meet this goal, SOMEEC gathered a group of specialists in the area of cardiology, electrophysiology, neurology and hematology that given their experience in certain areas, they share the scientific evidence with the panel of experts to leave open a discussion about the information presented in this article. This document brings together the best scientific evidence available and aims to be a useful tool in the decision to use of new oral anticoagulants in nonvalvular atrial fibrillation and ischemic heart disease, or relating to the management of patients with stroke or renal failure, and even those that will be submitted to elective surgery and invasive procedures. In the same, they handled comparative schemes of follow-up and treatment which simplifies the decision making by the specialists participants.

Underuse of Oral Anticoagulants for Nonvalvular Atrial Fibrillation: Past, Present, and Future.

Nonvalvular atrial fibrillation (AF) is the most widespread cardiac arrhythmia of clinical significance worldwide, and its prevalence is increasing.1,2 Atrial fibrillation is a substantial health problem because it significantly increases the risk of thromboembolic events, particularly that of stroke.3 Moreover, strokes associated with AF are more severe, involve larger vascular territories, and cause more morbidity and death than do strokes from other causes.4

Vitamin K and non-vitamin K antagonist oral anticoagulants for non-valvular atrial fibrillation in real-life

BackgroundCurrent guidelines recommend vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). MethodsWe compared the clinical features of consecutive in- and out-patients with non-valvular AF newly-treated with NOACs or on treatment with VKAs. ResultsOverall, 1314 patients newly-treated with NOACs and 1024 on treatment with VKAs were included in the study. The mean CHA2DS2-VASc score was 4.3±1.5 and 4.0±1.5 and the mean HAS-BLED score was 2.8±1.2 and 2.2±1.1 in the two groups, respectively (both p<0.001). Hypertension, previous stroke, female gender, vascular diseases and previous bleeding were more prevalent in NOACs patients. Renal failure, age ≥75years and congestive heart failure were more prevalent in VKAs patients. Among NOACs patients, 438 were given dabigatran, 463 rivaroxaban and 413 apixaban (33%, 35% and 31%, respectively). The mean CHA2DS2-VASc and HAS-BLED scores were higher in rivaroxaban or apixaban patients compared with dabigatran (both p<0.001) and VKAs patients (both p<0.001). A lower mean age was observed in patients newly-treated with dabigatran. Patients newly-treated with reduced doses of NOACs (599 patients, 45.5%) had a higher CHA2DS2-VASc (4.8±1.4 vs. 3.9±1.5 vs. 4.0±1.5) and HAS-BLED (2.9±1.1 vs. 2.8±1.2 vs. 2.2±1.1) scores compared with those treated with regular doses of NOACs or VKAs. ConclusionPatients given rivaroxaban and apixaban in clinical practice have a higher thrombotic and hemorrhagic risk in comparison with patients given dabigatran or VKAs. A considerable proportion of patients receive reduced doses of NOACs.

On the Way to a Better Use of Anticoagulants in Nonvalvular Atrial Fibrillation. Proposed Amendment to the Therapeutic Positioning Report UT/V4/23122013

On the Way to a Better Use of Anticoagulants in Nonvalvular Atrial Fibrillation. Proposed Amendment to the Therapeutic Positioning Report UT/V4/23122013

A Case of Periprocedural Discontinuation of Apixaban Resulting in Intra-aortic Thrombosis

Apixaban, a novel oral anticoagulant is approved for anticoagulation in non-valvular atrial fibrillation. Apixaban is found to be superior to warfarin in prevention of stroke and thromboembolism and is associated with lesser risk of bleeding. Peri-procedural discontinuation of apixaban is safe, but the risk of thrombosis exists. We here present a case of arterial thrombosis that lead to lower limb ischemia upon periprocedural discontinuation of apixaban.

Does novel oral anticoagulant improve anticoagulation for non-valvular atrial fibrillation associated stroke: An inpatient registration study in Shanghai

sObjectiveTo summarize the use rate, safety, efficacy of antithrombotics in stroke/transient ischemic attack (TIA) prevention, and reasons for not using dabigatran etexilate (DE) in Shanghai, China.MethodsNon-valvular atrial fibrillation (NVAF)-associated stroke patients were prospectively registered as an electronic database. Use rate of antithrombotics and reasons for not using DE were extracted during follow-up. Patients' baseline characteristics, recurrent ischemic stroke/TIA events and bleeding complications were analyzed.PatientsFrom April 2012 to August 2014, 110 inpatients with NVAF-associated stroke were studied in our hospital. NVAF was diagnosed by 12-lead electrocardiogram, 24 h Holter and echocardiography.ResultsBefore introduction of DE (April 2013), use rates of warfarin and antiplatelets were 28.9% (11/38) and 60.5% (23/38) respectively; after that, use rates of warfarin, DE, and antiplatelets were 20.8% (15/72), 12.5% (9/72), and 43.1% (31/72). The DE did not improve use of anticoagulants (P = 0.639). There were 19 (17.3%) recurrent ischemic stroke events up to October 2015; two (9.5%) in the non-user group, 10 (18.5%) in the antiplatelet group, and seven (20.0%) in the anticoagulants group (P = 0.570). Furthermore, recurrence rates were similar between the DE group (20.0%) and the Warfarin group (20.0%, P = 1.000). The most common reason for not using DE was financial concerns (61.0%), followed by inconvenience to purchase (14.0%) and hemorrhage concerns (11.0%). Two patients using warfarin found fecal occult blood so they stopped warfarin and began to use antiplatelet drugs. No bleeding event occurred in the other groups. Only one patient had side effects (dyspepsia and gastroesophageal reflux) from DE.ConclusionThe use rate of either DE or warfarin in Shanghai was low; DE had not improved anticoagulation therapy for NVAF patients in Shanghai mainly because DE had not been covered by health insurance.

Relative efficacy and safety of non-Vitamin K oral anticoagulants for non-valvular atrial fibrillation: Network meta-analysis comparing apixaban, dabigatran, rivaroxaban and edoxaban in three patient subgroups

BackgroundStroke is the most serious clinical consequence of atrial fibrillation, which is the most common cardiac arrhythmia. Non-vitamin K antagonist oral anticoagulants (NOACs) have emerged as efficacious, safe and convenient stroke prevention agents. This updated network meta-analysis focused on the relative efficacy and safety of apixaban compared with dabigatran, rivaroxaban and edoxaban for stroke prevention in (i) patients with CHADS2 score ≥2, (ii) secondary stroke prevention, and (iii) patients with high quality anticoagulation control with warfarin. Methods and resultsA fixed-effects network meta-analysis was conducted, including data from four Phase III randomised controlled trials (>70,000 patients with non-valvular atrial fibrillation). The results of the base-case analysis comparing NOACs with warfarin were broadly in line with the results from the individual trials.Results from the three subgroup analyses were broadly similar to the base case results. For example in patients with CHADS2 score ≥2, apixaban, high-dose dabigatran, rivaroxaban, and high-dose edoxaban had significantly lower hazards of stroke/systemic embolism compared with low-dose edoxaban. Apixaban and low-dose edoxaban were associated with significantly lower hazards of major bleeding compared with rivaroxaban and dabigatran 150mg. However, several treatment comparisons that were significant in the base-case analysis were not significant in the patient subgroups, due to the reduced sample size of the subgroups compared with the overall population. ConclusionsAmong the NOACs, apixaban offered the most favourable efficacy and safety profile in the overall patient population as well as in the three subgroups investigated.

Patient Profile of New Users of Novel Oral Anticoagulants in non-Valvular Atrial Fibrillation (Nvaf): Real-World Evidence from Primary Care Data in Germany

Patient Profile of New Users of Novel Oral Anticoagulants in non-Valvular Atrial Fibrillation (Nvaf): Real-World Evidence from Primary Care Data in Germany

Resident Physicians Choices of Anticoagulation for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF) is a common cardiac arrhythmia and is associated with an increased risk of ischemic stroke. The aim of this study was to identify practice patterns of Canadian resident physicians pertaining to stroke prevention in nonvalvular AF according to the Canadian Cardiovascular Society guidelines. A Web-based survey consisting of 16 multiple-choice questions was distributed to 11 academic centres. Questions involved identification of risks of stroke, bleeding, and selection of appropriate therapy in clinical scenarios that involve a patient with AF with a Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS2) score of 3 and no absolute contraindications to anticoagulation. There were 1014 total respondents, of whom 570 were internal, 247 family, 137 emergency medicine, and 60 adult cardiology residents. For a patient with a new diagnosis of AF, warfarin was chosen by 80.3%, novel oral anticoagulants (NOACs) by 60.3%, and acetylsalicylic acid (ASA) by 7.2% of residents. To a patient with a history of gastrointestinal bleed during ASA treatment, warfarin was recommended by 75.1%, NOACs by 36.1%, ASA by 12.1%, and 4% were unsure. For a patient with a history of an intracranial bleed, warfarin was recommended by 38.8%, NOACs by 23%, ASA by 24.8%, and 18.2% were unsure. For a patient taking warfarin who had a labile international normalized ratio, 89% would switch to a NOAC and 29.5% would continue warfarin. This study revealed that, across a wide sampling of disciplines and centres, resident physician choices of anticoagulation in nonvalvular AF differ significantly from contemporary Canadian Cardiovascular Society guidelines.

The fifth anniversary of clinical use of new oral anticoagulants in non-valvular atrial fibrillation

The possibilities of antithrombotic therapy for prevention of thromboembolic events in non-valvular atrial fibrillation (AF) have been significantly expanded after the development and introduction of new oral anticoagulants (NOACs) into clinical practice. Starting the clinical use of NOACs has opened a new page in oral anticoagulant therapy aimed at preventing thromboembolic events in AF. Dabigatran etexilate is the first NOAC that was registered in 2010. After completion of the RE-LY trial, the positive safety and efficacy profile of dabigatran has been confirmed in real practice of over 5 years of clinical use in more than 200,000 patients from nearly 100 countries. An observational cohort study of oral anticoagulants used in more than 134,000 patients was one of the largest independent studies of the Food and Drug Administration (FDA) in the Medicare system. In the dabigatran group, the risk of ischemic stroke, intracranial and intracerebral hemorrhage, and death was statistically significantly lower than in the warfarin group. The incidence of major and all hemorrhages requiring hospitalization, as well as myocardial infarction was comparable. Profuse gastrointestinal bleeding was more common with dabigatran. This study in the Medicare system has demonstrated a favorable benefit/risk ratio for this drug and this requires no additional changes in the current instructions and recommendations for its use.

Major bleeding risk assessment in atrial fibrillation patients taking vitamin K antagonists

Background. The use of risk scores for the assessment of major bleeding and stroke in patients with atrial fibrillation (AF) helps evaluate the risks and benefits of oral anticoagulation therapy. The aim of this study was to describe the percentage of patients receiving anticoagulants for non-valvular AF with a high risk of major bleeding based on the HAS-BLED score, as well as identify potential modifiable risk factors of bleeding and compare the risk of major bleeding with the risk of stroke. Methods. Retrospective cohort study involving patients of the anticoagulation outpatient clinic of the Division of Internal Medicine at Hospital de Clinicas de Porto Alegre. Major bleeding risk was estimated based on the HAS-BLED score and stroke risk was determined using the CHADS 2 and CHA 2 DS 2 -VASc scores. Results. Sixty-three patients were investigated (mean age 74.3±10.9 years). The median HAS-BLED score was 2 points, 19 (30.2%) patients had a score ≥ 3 (high risk). The most prevalent modifiable risk factors were labile TP/INR (36.5%) and concomitant use of drugs (30.2%). The absolute risk of major bleeding based on the HAS-BLED score was higher than the risk of stroke in three (4.8%) and four (6.3%) patients in comparison with the CHADS 2 and CHA 2 DS 2 -VASc score, respectively. Conclusions. We concluded that the percentage of patients with high risk of major bleeding is similar to the rate found in the national literature (30.2%). In addition, the most prevalent modifiable risk factors in our cohort were labile TP/INR and concomitant drug use.

New oral anticoagulants for nonvalvular atrial fibrillation in the elderly: Limited applicability in primary care

Background: Based on the results from randomized controlled trials (RCTs), new oral anticoagulants (NOACs) seem attractive alternatives to vitamin K antagonists (VKAs) because of their effectiveness, safety, and ease of use. However, the use of NOACs in unselected elderly patients with atrial fibrillation (AF) in primary care is arguable.Objectives: To assess the evidence for the effectiveness and safety of NOACs compared with VKAs in elderly patients with nonvalvular AF in primary care.Methods: Starting from the meta-analysis of Ruff et al. (Lancet 2014;383:955–62), we used the GRADE-approach to make a transparent and explicit judgement of the quality of evidence.Results: The meta-analysis reviewed four non-inferiority RCTs, including 58 634 AF patients with an average age of 70–73 years. Inconsistency of results, indirectness of evidence, and imprecision of risk reductions resulted in downgrading of the quality of evidence available from these studies. The quality of evidence for a decrease in all-cause stroke and systemic embolism (RR: 0.81; 95%CI: 0.73–0.91) for elderly patients using NOACs compared to VKAs in routine primary care was low. The quality of evidence for a lower risk for haemorrhagic stroke (RR: 0.49; 95% CI: 0.38–0.64) and for a lower risk of intracranial bleeding (RR: 0.48; 95% CI: 0.39–0.59) was moderate.Conclusion: There is uncertainty about effectiveness and safety of NOACs in unselected elderly patients with AF in primary care. Therefore, the balance between benefit and harm is still unclear. For this reason, routine use of NOACs is not recommended in elderly patients in primary care.

Current guidelines and prospects for using novel oral anticoagulants for nonvalvular atrial fibrillation

The capabilities of antithrombotic therapy to prevent systemic thromboembolic events in nonvalvular atrial fibrillation (AF) are substantially extended after clinically introducing novel oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, and apixaban. World clinical experience with NOACs in AF has confirmed their efficacy and safety in both primary and secondary stroke prevention. At the same time, apixaban additionally reduces the risk of fatal outcomes and it is the safest among the NOACs against hemorrhagic events. The low risks of intracranial hemorrhage typical of NOACs should be taken into account when choosing oral anticoagulant therapy after hemorrhagic stroke in patients at high risk for thromboembolic events due to AF. Whether NOACs may be used in acute myocardial infarction and during coronary stenting in the presence of nonvalvular AF, left ventricular thromboses, and cardiomyopathies is considered. In real clinical practice, nonvalvular AF may be accompanied by different cardiovascular diseases, by creating the situations where there are no specific guidelines for the use of NOACs. The results of comparing the clinical efficiency of different antithrombotic therapy regimens, the subanalysis of randomized trials, and experts’ opinions may assist a physician to substantiate their decisions. Thus, just a few NOACs that are similar and/or superior to warfarin in efficacy and safety have emerged to date. There are grounds to believe that many physicians will prefer direct anticoagulants to warfarin not only because of their proven efficacy, but also the rapid onset of their anticoagulant effect, neither interaction with a number of foods or drugs, and above all, nor need for regular laboratory blood testing. World post-marketing surveillance and new clinical tests will be helpful in better estimating the benefits and risks of treatment with NOACs and in expanding indications for their use, which will considerably enhance the possibilities of preventing thromboembolic events in cardiac pathology in the period ahead.

More Data on Left Atrial Appendage Occlusion

Many patients and physicians are interested in finding a safe, effective alternative to oral anticoagulation for nonvalvular atrial fibrillation

Safety and efficacy of non-vitamin K oral anticoagulants in non-valvular atrial fibrillation: a Bayesian meta-analysis approach

Introduction: Choosing between different non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) is difficult due to the absence of head to head comparative studies. We performed a Bayesian meta-analysis to explore similarities and differences between different NOACs and to rank treatments overall for safety and efficacy outcomes.Areas covered: Through a systematic literature search we identified randomized controlled Phase III trials of dabigatran, rivaroxaban, apixaban, and edoxaban versus adjusted-dose warfarin in patients with NVAF.Expert opinion: Warfarin ranked worst for all-cause mortality and intracranial bleedings and had a nil probability of ranking first for any outcome. The risk of major bleeding versus warfarin was lower with apixaban, dabigatran 110 mg, and both doses of edoxaban. All agents reduced the risk of intracranial bleeding versus warfarin. Edoxaban 30 mg was the best among the treatments being compared for major and gastrointestinal bleeding. Dabigatran 150 mg was the best for stroke and systemic embolism. This study suggests that NOACs are generally preferable to warfarin in patients with NVAF. However, safety and efficacy differences do exist among NOACs, which might drive their use in specific subsets of AF patients, allowing prescribers to tailor treatment to distinct patient profiles.

Beyond warfarin: A patient‐centered approach to selecting novel oral anticoagulants for stroke prevention in atrial fibrillation

Warfarin reduces stroke in patients with atrial fibrillation. However, its narrow therapeutic index and need for chronic monitoring are barriers to its optimal utilization in many patients. The recent introduction of 3 novel oral anticoagulants (NOACs), as alternatives to warfarin, may change the eligibility and management of patients with nonvalvular atrial fibrillation (NVAF) who require systemic anticoagulation. To summarize contemporary indications for anticoagulation in NVAF, and to help provide patient-centered clinical decision making for selecting warfarin or 1 of the NOACs (dabigatran, rivaroxaban, apixaban) based on randomized trials and mechanistic data for each drug. The primary clinical outcome trials of warfarin and the NOACs, pharmacologic studies, and briefing documents from the US Food and Drug Administration were reviewed. In randomized trials, NOACs were consistently noninferior to warfarin for reducing stroke or systemic embolism in patients with NVAF, with reductions in intracranial bleeding as well. However, NOACs have several important drug-drug interactions, exclusion criteria for specific patient subgroups (eg, severe renal disease), and each medication may have a different impact on other clinical outcomes such as myocardial infarction or gastrointestinal bleeding. Benefits of the new drugs are particularly pronounced when international normalized ratio levels on warfarin are labile. Warfarin continues to play an important role in the prevention of stroke or systemic embolism in NVAF. Among selected patients, the use of NOACs provides equal or superior benefit, without the need for chronic anticoagulation monitoring or ongoing dose titration.

Novel oral anticoagulants in non-valvular atrial fibrillation.

Atrial fibrillation is the most frequent arrhythmia in clinical practice, reaching 2% of the people in the world and is associated with systemic embolism. Thus, the use of anticoagulants is indicated if CHA2DS2-VASc score ≥2 or in patients with previous transient ischemic attack or stroke. For decades, warfarin, a vitamin K antagonist, was the only choice for chronic oral anticoagulation. Recently, novel oral anticoagulants (NOACs) have been introduced, offering similar (or better) effectiveness, safety, and convenience to the vitamin K antagonists. Dabigatran was the first NOAC approved and is a direct thrombin inhibitor. Rivaroxaban and apixaban are factor Xa inhibitors. They display rapid onset of action, more predictable of pharmacological profile, less interactions with other drugs, lack of significant effects in the diet, and less risk of intracranial hemorrhage than warfarin. Despite that dose adjustment is necessary for patients with chronic kidney disease or according to body weight, these new drugs do not require regular monitoring. There are recommendations for the start and follow-up therapy with NOACs, planning for cardioversion, ablation and surgical interventions and the management of bleeding. This article is a review of the major studies of the NOACs. The clinical use of these drugs in patients with non-valvular atrial fibrillation is presented.

Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups

Background. New oral anticoagulants (NOAC; rivaroxaban, dabigatran, apixaban) have become available as an alternative to warfarin anticoagulation in non-valvular atrial fibrillation (NVAF). Methods. MEDLINE and CENTRAL, regulatory agencies websites, clinical trials registers and conference proceedings were searched to identify randomised controlled trials of NOAC versus warfarin in NVAF. Two investigators reviewed all studies and extracted data on patient and study characteristics along with cardiovascular outcomes. Relative risks (RR) and 95% confidence intervals (CI) were estimated using a random effect meta-analysis. Results. Three clinical trials in 50,578 patients were included. The risk of non-hemorrhagic stroke and systemic embolic events (SEE) was similar with the NOAC and warfarin (RR = 0.93; 95% CI = 0.83–1.04), while the risk of intracranial bleeding (ICB) with the NOAC was lower than with warfarin (RR = 0.46; 95% CI = 0.33–0.65). We found differences in the effect size on all strokes and SEE depending on geographic region as well as on non-hemorrhagic stroke, SEE, bleeding and mortality depending on time in therapeutic range. Conclusion. The NOAC seem no more effective than warfarin for prevention of nonhemorrhagic stroke and SEE in the overall NVAF population, but are generally associated with a lower risk of ICB than warfarin.

Restarting Anticoagulation and Outcomes After Major Gastrointestinal Bleeding in Atrial Fibrillation

Data regarding the outcomes of restarting anticoagulation in patients who develop gastrointestinal bleeding (GIB) while anticoagulated are sparse. We hypothesized that restarting anticoagulation in these patients is associated with better outcomes. This is a retrospective cohort study that enrolled subjects who developed GIB while on anticoagulation from 2005 to 2010. Atrial fibrillation was defined by history and electrocardiography on presentation. GIB was defined as a decrease in hemoglobin by 2 g, visible bleeding, or positive endoscopic evaluation. Time-to-event adjusted analyses were performed to find an association of restarting warfarin and recurrent GIB, arterial thromboembolism, and mortality. Stratified analysis by duration of interruption of warfarin was also performed. Overall, 1,329 patients (mean age 76 years, women 45%) developed major GIB. Warfarin was restarted in 653 cases (49.1%). Restarting warfarin was associated with decreased thromboembolism (hazard ratio [HR] 1.18, 95% confidence interval [CI] 0.75 to 1.84, p = 0.47) [corrected] and reduced mortality (HR 0.67, 95% CI 0.56 to 0.81, p <0.0001) but not recurrent GIB (HR 1.18, 95% CI 0.94 to 1.10, p = 0.47). When the outcomes were stratified by duration of warfarin interruption, restarting warfarin after 7 days was not associated with increased risk of GIB but was associated with decreased risk of mortality and thromboembolism compared with resuming after 30 days of interruption. Decision to restart warfarin after an episode of major GIB is associated with improved survival and decreased thromboembolism without increased risk of GIB after 7 days of interruption.